PM1b Spring Term - T/E/S/I Flashcards

Question

Discuss thermodynamically favourable direction

Answer 1

So in this graph we have Gibbs free energy, so the total amount of energy in the system against the extent of the reaction zero being the point where we have 100% reactants on 1 being where the proportion of products is 100%. So you can see that for an equilibrium reaction, the lowest point of the curve will not be at the point where we have products formed. It will be somewhere between where products and reactants are. So it'll show that there is a proportion of both reactants and products at that lowest energy point. And that would be the equilibrium point. For the forward reaction, the standard change in Gibbs free energy for this reaction is -32.9. So this is the reaction we're going to focus on: formation of ammonia. This means that it is an exothermic reaction - going from reactants to products. The reactants have a higher total energy compared to the products. So you can see that the line at the zero-point on our progress of reaction- a graph here will be higher than when it gets to the end where we have 100% products, where the line is lower because the overall change in Gibbs energy for the overall reaction is a negative number. If we think about how Gibbs energy changes during that forward reaction in the formation of ammonia, we see that we get a decrease in G as we go towards that minimum point and then we see that G, the Gibbs energy, increases. At the point of equilibrium, we have our minimum point and so the change in Gibbs free energy at that point of minimum, is zero. At any point on this graph, we can see that the gradient will tell us whether we expect the reaction to be going more in the forward direction or more in the backwards direction, to get to that minimum point. (2) For the forward reaction, the standard change in Gibbs free energy for this reaction is -32.9 – meaning it is exothermic in the forward direction and the reactants have a higher total energy compared to the product. However, the minimum energy is a point where both reactant and product is present as this is an equilibrium reaction. And if we think about how Gibbs energy changes during the forward reaction in the formation of ammonia – we see the delta G decreases to equilibrium point but beyond that Delta G increases. At point of equilibrium Gibbs energy is at lowest point and thus Delta G will be zero (the gradient is zero at this point). At any point on this graph we can see from the gradient whether we expect the forward or reverse reaction to dominate.

Answer 2

The direction of changes depends on the ratio of concentration of reactants and products. The quotient defines that ratio at any point along the progress of reaction path. For the reaction forming ammonia the quotient is given here. The quotient is the concentration of products raised to power of stoichiometry of the reaction (so 2 molecules of ammonia form in this reaction so the concentration is squared). The products are divided by the concentration of the reactants again raised to powers coming from stoichiometry of the reaction.

Answer 3

So how does delta G change? As we said before, in the reaction equilibrium, there'll be a minimum point on our free energy graph where the change in Gibbs energy is zero. That was our equilibrium point. But our quotient can be measured at any point along that graph where we might want to determine whether the reaction is favored going towards reactants or towards products. With the quotient, we have a way of determining how delta G changes at any of these points along that progressive reaction graph. G changes, as we know to a minimum, which is somewhere between reactants and products. The change of G will be negative before the minimum points and positive afterwards. We can use this equation here, which tells us how G will change going along that curve and link it to standard conditions change in Gibbs free energy, which is the Gibbs free energy for the total reaction going from reactants to products. Adding to that a component, which will tell us where we are on that curve because it's linked to the quotient, then we will be able to see whether delta G is negative or positive and therefore the direction of travel for the reaction at that point. We know that the standard change in Gibbs energy to form products is negative for this reaction. The delta G at any point along the reaction can be calculated if we can determine the quotient at that point to using this equation.

Answer 4

So we can work out where we are along the reaction. The reaction will go towards products. When some of the two components, the standard Gibbs energy change and the term with the quotient on negative. At equilibrium, the change in Gibbs energy is zero. If we are at a point further along the progress of reaction, (the equilibrium), then delta G will become positive in the forward direction, meaning that the reaction doesn't anymore favor going from reactants to products and now favors going from products to reactants.

Answer 5

,any point we do not lead to a static situation. We are looking at two reactions- one going from reactant to product and one going from products to reactants. Equilibrium is not static. You can think of it as though as a position of calm. If the amount of work you are being asked to do is comfortably equal to the rate that you can get the work done – its calm. It's not a static state, is a dynamic state, but it is calm because you're intray is building up as fast as your out tray. So you don't get overwhelmed and you're at a system of equilibrium. But you're not doing nothing. And that's the same for these reactions. If you see here, these two graphs show that. So you can see here rate of the reactions against time, in the the rate of the forward reaction, if you start with 100% reactants, initially the rate of the forward reaction will be greater than the rate of the reverse reaction because you will have more reactants than products. But at some point the rate of both the forward and the reverse reactions will equal. That is where you have equilibrium. If you see that as the amount of reactants and products is formed, you get to a point where there are reactants present and products present. But the total amount of both is not changing. At equilibrium, the quotient is given a different letter, its given the letter K. And it becomes the equilibrium constant. And at equilibrium, the change in G Gibbs energy is also zero. So this means our quotient equation changes and simplifies. Because delta G is now zero, zero equals all standard Gibbs free energy change for the total reaction plus RT. And now we have log of K rather than natural log of Q. So LN is natural log, and I often just shorthand say log- natural log of K. You can rearrange that to get a really important equation that links the the change in Gibbs free energy for our reaction to the equilibrium constant minus RT. R is the gas constant times temperature times the natural log of K, (the equilibrium constant). So that's our first really important equation, link to equilibrium.

Answer 6

In summary, K is the quotient at equilibrium If you calculate Q for particular point in a reaction and Q < K, the reaction will proceed in direction of products. If Q > K, the reaction will proceed in direction of reactants. At equilibrium this equation is true – we can now link the equilibrium constant (and therefore the ratio of product over reactant concentrations at equilibrium) to the standard change in Gibbs free energy for the reaction.

Answer 7

So considering the use of baking soda in baking, this reaction is an equilibrium reaction, releasing carbon dioxide and water. However, at room temperature, the equilibrium constant is ten to the minus seven. You'll see that in the slide: 4.9 times ten to the minus seven. So it's very, very small. In fact, it is so small that if you think of products over reactants, we are dominating as reactants. It's a very small number over a very large number. So you could say that this reaction has not occurred at all. And you'll notice that at room temperature, delta G for the reaction is plus 36. So also saying the reaction doesn't occur. You need higher temperatures for this reaction to occur and for this equilibrium to shift to a point where products are forming. At higher temperatures, we then see that the equilibrium constant shifts to 55. So now there's more products than reactants at equilibrium. There's still component of both. That number isn't ridiculously high to say there is no reactants. And you'll notice that the Gibbs free energy for the reaction is now a negative number. So you can see that the equilibrium constant changes with temperature. It is not constants at different temperatures, it's only constant at a single temperature. You can also see that baking soda doesn't work unless you have it in an oven or in a system where it's warm enough for the reaction to occur. If you want to maximize the product, then you need to think about how different variables shift this equilibrium position. That is Le Chatelier's principle.

Answer 8

Here we have a reaction and we're going back to formation of ammonia reaction again: nitrogen plus hydrogen. The nitrogen is blue, hydrogen is black. You can see that at the start we have high concentrations of nitrogen and hydrogen and low concentrations of ammonia. As the reaction proceeds, the concentration of the product increases. The concentration of the reactants decrease until you get to a point of equilibrium when the concentrations of all three are not changing. What if you now add to this system more of one of the reactants? So here we're going to add to the system a higher concentration of hydrogen. This will alter the equilibrium and now we'll get further reaction until equilibrium is re-established. The same would happen if you at this point added some ammonia to this system (so you've added some product to the system) and so the reaction would spontaneously shift again until the system has reached equilibrium. So as you change a component of the system, you shift the equilibrium and you'll get the reaction to move in one direction or the other depending on that change that you have made.

Answer 9

If temperature is increased or decreased we shift the equilibrium because Delta G depends on T and the equilibrium constant. By increasing the temperature we make the reaction take in heat and this will shift the reaction towards the endothermic direction. If the reaction in forward direction is exothermic, increasing the temperature shifts the equilibrium towards the reactants. So, this changes the ratio of products and reactants… so, changing temperature also changes K. if we increase the temperature? In an exothermic reaction going from reactants to products, the change in enthalpy will be negative and that means that the reaction produces heat. And the change going from products to reactants, where we will absorb heat, the change in enthalpy will be positive. So, by increasing the temperature we make the reaction take in heat. This will shift the reaction towards the endothermic direction. If the reaction in the forward direction is exothermic, increasing the temperature shifts the equilibrium towards the reactants, in the endothermic direction. This changes the ratio of products and reactants. Changing temperature also changes the equilibrium constant

Answer 10

This table here shows you how. You can see that if the reaction is endothermic in the forward direction then a temperature increase will increase the equilibrium constant. So if it increases the equilibrium constant, what does that mean in terms of the relative amounts of products and reactants at equilibrium? It means that there had been more products at equilibrium. If the temperature decreases, then the equilibrium constant decreases. For an exothermic reaction, then if you increase the temperature, the equilibrium constant will decrease. So you'll have less products compared to reactants. So it's shifting it towards the reactants. If you decrease the temperature, the equilibrium constant will increase. Now we can show the link between temperature and equilibrium constant in an equation. And this equation is using these two equations that we have already seen. So that's the equation that the change in Gibbs free energy is equal to minus RT natural log k. RT natural log k. And the change in Gibbs free energy is equal to the change in enthalpy minus the temperature times the change in entropy. So these two equations- if you can combine them, you will get the van't Hoff equation that will link equilibrium constant to temperature. With our two equations for change in Gibbs energy we can create an equation that can be used to calculate enthalpy through knowledge of K at two different temperatures

Answer 11

We can work out our thermodynamic values by carrying out two experiments of an equilibrium reaction at different temperatures and using these equations So, we measure K at T1 and T2 because we can measure the concentrations of reactants and products at equilibrium. We can then calculate Delta G using each of these data sets. The value will depend on temperature.

Answer 12

Experiment one- we've measured K1, at T1- at temperature one. And experiment two, we have measured K2 at temperature two. So we can do this because we can calculate the equilibrium constant for measuring the concentrations of reactants and products at equilibrium. We can now easily calculate the change in Gibbs free energy, delta G, we can calculate this at both temperatures using this equation. We can calculate Delta G T1 using the experiment one data, or delta G T2 using experiment two data. We're not assuming that Delta G is the same at different temperatures. We know that it will not be. We can work out the enthalpy, the change in enthalpy from van't Hoff equation. All of the values in this equation are known. We have the gas constant, which is known, and we have the equilibrium constants, the two temperatures of our measurements, which are all known. We can use this equation to work out the change in enthalpy. So we can work out Delta H from this equation.

Answer 13

The final thermodynamic parameter can now be calculated, and that is Delta S, which can be determined from this equation. It is now the only unknown term. And we can work it out using data at temperature one or data for Delta G at temperature T2. And you should get the same value for Delta S, whichever you use. As mentioned earlier, delta H and delta S are assumed to be temperature independent for these calculations.

Answer 14

Example: The formation of NaCl(s) from its elements is spontaneous and releases a great deal of heat. Na(s) + Cl2(g) → 2NaCl(s)This process involves a gas molecule becoming a solid, and therefore must involve a decrease in entropy. Therefore, ΔS is negative. It is an exothermic reaction, releasing heat, therefore ΔH must also be negative. This reaction is 'driven by enthalpy', because the large negative ΔH is more negative than the -TΔS term is positive, resulting in a negative overall ΔG and a spontaneous reaction. Examples: -30.2 = -88.7 – (-58.5) As 88.7 > 58.5, this is enthalpy driven -30.2 = 88.7 – (118.9) As 88.7 < 118.9, this is entropy driven Transcript So in summary, we can work out K at equilibrium constant from the concentrations of reactants and products. We can, we can determine delta G from those two values at one temperature and we can repeat that to determine delta G for the other temperature. We can use van't Hoff equation to obtain delta H. Then we can work out Delta S. Now we can work out the dominant contribution of delta G for the reaction. Determine if it is enthalpically or entropically driven. Remember, if delta H is negative and minus T Delta S is less negative or is positive, then we would know that the processes are enthalpically driven. Whereas if delta S is positive, so that minus T Delta S is very negative and Delta H is positive, so in other words, the enthalpy is endothermic, we would know that we had a process that was entropically driven. In other words, the reason why the reaction occurs is because of a change in entropy. So an increase in disorder of the system rather than the change in enthalpy. This helps us to understand that binding process or that interaction that allows the reaction to occur. So the easiest thing to do when you're thinking through what I've just said in terms of how delta H and delta S changes, think using this equation: delta G equals delta H minus T Delta S. S. And remembering that for the reaction to occur spontaneously, delta G needs to be negative. And we will know whether it's enthalpically or entropically driven based on whether it is the Delta H component or the minus T Delta S component that gives delta G its negative value. That is the end of that topic. I'm going to finish this lecture by talking about a different type of equilibrium process.

Answer 15

we can use the concepts of equilibrium that will have learned to consider equilibrium partitioning of a drug between two phases- an aqueous phase and an organic phase. Now this allows us to understand if the drug is more lipophilic, so lipid oil liking, in other words, it would reside in the organic phase or whether it is more hydrophilic, where it would reside or prefer to reside in the aqueous phase. And this is a concept we use to determine how well a drug might partition across a membrane and be absorbed into the bloodstream. In this diagram the drugs starts in the aqueous phase. We will be able to see it move or partition into the organic phase until an equilibrium is reached. So, you can see that molecules will gradually cross into the organic phase. These are two immiscible phases, so they don't mix, until we get to a point of equilibrium where the same number of molecules are going from the aqueous phase to the organic phase than are going from the organic phase to the aqueous phase. At this point we have equilibrium. And you can see that in our equilibrium points, there are more molecules now in the organic phase. So this molecule is fairly lipophilic, likes the organic phase more than the aqueous phase, but it is soluble in both phases (2) This process is a physical, as in it's not a chemical reaction equilibrium. It's a physical equilibrium. As we go to a point where we have partitioning at equilibrium of all molecules between the two phases. As we know for a reaction, the equilibrium constant is products over reactants. So for this equilibrium partitioning, the equilibrium constant, which is now known as the partition coefficient, is calculated - concentration of drug in the organic phase over concentration of drug in the aqueous phase at equilibrium. So it's the same structure of an equation that we would see for our equilibrium constant. So the partition coefficient is our physical equilibrium constant here. It is the concentration in the organic phase over the concentration of drug in the aqueous phase.

Answer 16

So in this example, we started with 12 X's. So 12 molecules in our aqueous phase, as you remember, and an equilibrium, there were three molecules, three x's in the aqueous phase, and nine x's in the organic phase. So that means our partition coefficient is 9/3- is three. This is, as you can see, a relatively large number is above one. So it shows that the drug has a preference for the organic phase, for the lipid phase.

Answer 17

The process of dissolution involves breakage of solute-solute and solvent-solvent bonds – both endothermic processes and the formation of bonds between solute and solvent with the liberation of energy. For dissolution to occur DeltaG must be negative and thus there must be a balance between the enthalpy of dissolution and the associated entropy. Solubility of a chemically related series are inversely related to their melting points, because the removal of solute molecule from solid reflects the strength of interaction between solute molecules – so how easily from an energetic point of view that the solid melts. From a structural point of view, you may know already the impact different functional groups have on solubility in water. Substituent groups: -polar groups impart high solubility due to capability of strong bonding with water so DeltaH for solven-solute bond is negative. Non-polar groups –CH3 and-Cl impart low solubility because of poor interaction between solute and solvent. Ionisation of groups –COOH and –NH2 are slightly hydrophilic whereas –COO(-) and –NH3(+) are very hydrophilic Possition of substituent on group can also influence solubility Solubility of acids and bases are pH dependant – represents the vast majority of active ingredients: solublity increases with degree of ionisation: at pH above pKa, solubility of acidic drugs increase and at pH values below pKa solubility of basic drugs increase; where the molecule is zwitterionic the molecule behaves as an acid at basic pH and as a base at low pH (minimal solubility in range between pKa’s of the acid and basic groups) Hydrotropy: increase in solutes due to the salting in affect of salts that are themselves very soluble in water (structure makers)

Answer 18

SO, we now know that changes in DeltaH for breaking the lattice structure and deltaH for solvation often leads to an overall +ve change in terms of Delta H so the dissolution is usually controlled by entropy change. SO TDeltaS has to be larger than the deltaH term for DeltaG to be negative. Let’s consider this in a different way - consider solute = A, solvent = B: If forces holding A to A are very strong compared to the forces that hold A to B, the solute won’t break down and form a solution If forces holding B to B are very strong compared to the forces that hold A to B, the solvent won’t accept solute If forces that hold A to B are greater than those holding A to A and B to B, A will dissolve in B So the properties of the solute, the dissolving species and the properties of the solvent will determine solubility. Lets look at the solute first: As mentioned previously, melting point of the solid relates to solubility Melting is breaking the inter molecular bonds in a particle (crystal) Melting point reflects the scale of inter molecular interactions So melting point can be used to predict solubility and so will the crystal structure and molecular structure. We have briefly discussed how functional groups can lead to solubility, but also how the crystal lattice is put together will impact on how easily the intermolecular interactions within the lattice break Finally particle size will impact the rate of dissolution and thus solubility The solvent temperature affects solubilty As earlier, increasing temperature usually increases solubility since normally ΔH +ve, dissolution is endothermic, takes in heat, so increasing temperature will increase solubility If ΔH -ve, dissolution is exothermic, gives out heat, increasing temperature decreases solubility Also, pH as this will change the ionisation of weak electrolytes The solvent itself is clearly important – but if you add co-solvents or exhipients to the solvent you can change the dielectric constant of the solvent as a whole – the solvents polarity – and this will alter solubility.

Answer 19

If drugs are weak electrolytes their solubility changes with pH Weak electrolytes represent the vast majority of active ingredients: solubility increases with degree of ionisation: at pH above pKa, solubility of acidic drugs increase and at pH values below pKa solubility of basic drugs increase; where the molecule is zwitterionic the molecule behaves as an acid at basic pH and as a base at low pH (minimal solubility in range between pKa’s of the acid and basic groups) Within 2 pH units either side of pKa – partial dissociation; at pKa 50% disassociated – use Henderson-Hasselbalch equation (lecture 3) to work out amount of each form at a particular pH Outside of this range then essentially completely unionised and ionised. Fully ionised will be the form with the maximum solubility for the molecule – so that is low pH for a weak base and high pH for a weak acid SO: acid drugs - unionised form in stomach so absorption in stomach; basic drugs – unionised form in intestine so absorption in intestine NB: quite a lot of drugs that are weak acids or weak bases. They'll have a COOH group in them. They have an amine in them. So we can say most drugs are weak acids or weak basis, which means that we have to think about the pH of the solution as well. Okay? Because a weak acid, as you know, will be in an equilibrium between its non-ionized form and its ionized form. And a weak base will be an equilibrium between its non ionized at its ionized form if it's in water. Okay. We've already seen that the ionized form of a drug is more soluble. So that means that solubility will be maximum when the drug is maximum ionized. Percentage ionized will be percentage of the maximum solubility, and that'll be the same. If you plot the percentage ionized of a drug against pH, you'll get, this is a way to think about it for the two different types of drugs. So if you have a weak acid, right? And your at low pH, you are at high hydrogen ion concentration. And so if you're at high hydrogen ion concentration, you're going to have the hydrogen ion connected to the acid. So it's not going to be ionized. Okay? If it's not ionized, is gonna be least soluble at that stage. However, that is for that molecule. As you get to the mid point, which is the PKA of the drug, that point, that is the pH, when the drug is 50 per cent ionised and 50 per cent not ionized. And then above that pH, we're going to be in a situation where the drug is in its ionized form and it's going to be the most soluble. Okay. I suppose just the opposite for a base. At low pH, we have high hydrogen ion concentration and we will see that in that case, we'll have the hydrogen ions stuck to the base. Okay? That means it'll be as ionized is, it can be 100% ionized and it'd be a soluble as it can be. And then at high pH, we have low hydrogen ion concentration. So the hydrogen ion will not be connected to the base. The base will be not charged, and then it will be the least soluble it can be. So we see this link between ionization of the drug and solubility of the drug. You could write solubility there instead. They'd be interchangeable on this diagram here. Now that's really useful because it means if we play around the pH, we can play around your solubility as well. So we can make a to salt form. We can just mess about with pH. We could change the crystal structure. These were all things that we can do that will change the solubility

Answer 20

Low pH means high H+ concentration and thus unionized form of the acid. High pH has low H+ concentration so the acid is ionized – loses its H+ So just an example for a particular drug here. This one has a pKa of 4.75, okay? So it's acetic acid. And you can see that this is how the ionization changes with pH. And this point here, the pH is 4.75, this midpoint here. The pH is 4.75. Now this is really important because of the number of times students have said this to me wrong. I'm now going to say something that's really important. The PKA does not tell you if a drug is a weak acid or a weak base. If you could just put that in capital letters somewhere in your notes, that would be really useful. The PKA does not tell you, the value of the PKA will not tell you if a drug is a weak acid or a weak base. The structure of the drug will, does it have an amine group in it? E.g. it's a weak base. Does it have a carboxylic acid in it? Is a weak acid. Does it have both in it? It's got basic properties and acidic properties, right? Okay, so we're going to talk about buffers now. So buffers are made up of two components. So if you're buffering a solution, you have to add two things. You have to either add a weak acid and its conjugate base, which is a salt. OR have to add a weak base and its conjugate acid, which of course is a salt. So you have to add an acid and a salt or a base and a salt to buffer a solution. Okay? So if we're talking about an acetate buffer, obviously that's based on acetic acid. It's got a pKa of 4.75, which I've just told you. Okay, the salt exists in its ionized form, doesn't it? Because that's why it's assault exists like this. So what this does by having it in the solution is it provides a huge amount of these ions. Yes. Okay. Acid is in equilibrium between an ionized form, in fact, those ions and a non-ionized form. If you add, change this solution by adding hydrogen ions, we're taking hydrogen ions away. You need to be able to shift this equilibrium to keep the pH the same. And you're only going to be able to do that if you have a huge number of these ions floating about. Okay? So that's why you need both. You need something that's in equilibrium, that can move to keep the hydrogen ions at a constant amount. And then you need a big pool of the other ion from your salt. So you need both. Okay? Another important thing about buffers is you've got to pick the right buffer. So if I was buffering something, and I wanted it at a pH of five, Acetate buffer would be perfect because it's PKA is 4.75, which is really close to five, right? And if you go back to this here, in this region in the middle here, you've got that equilibrium, haven't you? You've got some ionised and unionised in this middle bit here. Out here. There's no equilibrium, is it? So these sorts of PHs, it's 100% ionized. These sorts of pH is very low pHs, which is hundred percent un-ionized. So great to be able to buffer. It's got to be in this region here. So the PKAs important, this PKA is got to be close to the pH.

Answer 21

Buffer action: example weak acid and conjugate base. The conjugate base provides the acetate ions at appropriate high concentration. The acid is in equilibrium in ionic and unionized form and shifts to account for the ions coming from the conjugate acid (the salt) making it that both conjugate acid and the acid are in appreciable quantities and able to buffer (shift the equilibrium of the weak acid when a strong acid or base is added

Answer 22

A hydrotrope is a compound that solubilizes hydrophobic compounds in aqueous solutions This of course means that all additive or excipients within a formulation – ingredients other than the active could impact on the solubility of the active ingredient. We can add salt to modify solubility Salting out: when a salt is added to aqueous solution, the salt competes with solute for the water molecules, reduces solute solubility Salting in: some large anions / cations can increase solubility by hydrotropism e.g. adding sodium benzoate to aqueous solution increase solubility of caffeine

Answer 23

Like dissolves like” – solute dissolves best in a solvent with similar chemical properties A polar compound in a polar solvent e.g. lactose in water A non-polar compounds in a non-polar solvent e.g. a fat in an oil Adding a solvent (co-solvent) to water can improve the extent to which it is able to dissolve non-polar substances

Answer 24

In any physical process, solids (solutes) dissolve in a solvent to form solutions, the process known as dissolution The rate (the time to form a solution) is defined as the dissolution rate While solubility describes the total amount of drug that can dissolve in a finite volume of solvent, dissolution rate is about how fast the drug can dissolve,

Answer 25

The parameters that will affect the rate of dissolution include the particle size because the greater surface areas the material has the more contact with the solvent which will increase the speed of dissolution. lets consider a big particle with a large bulk volume and a relatively small surface area. If that same volume is split into smaller pieces we get to a point where there is more surface area than there is volume - and larger area accessible to solvent – thus increased rate of dissolution

Answer 26

Now if you consider a tablet it will disintegrate on contact with water and when it breaks open the molecules will be liberated from surface areas. If the drug concentration in solution near the surface is low then the concentration gradient will be significant allowing faster dissolution. To keep the concentration of drug near the surface of the particles to be low we need to think about the boundary layer There are a number of factors that need to be considered during this dissolution process that could affect dissolution rate e.g. Wetting of surface; if surface doesn’t “wet” then solvent can’t interact with solute to liberate from surface We can add surfactants (surface active agents) to help wet the surface Diffusion through boundary layer If slow, drug saturated in boundary layer, no more solute can dissolve Can decrease boundary layer thickness by stirring

Answer 27

The Noyes-Whitney equation considers all the variables that will affect the dissolution rate. dm/dt is the rate of change of mass so is the dissolution rate D is the diffusion coefficient – we mentioned that rate of diffusion from the drug concentrated area need the particle surface and the bulk solution (i.e. through the boundary layer) is important. The diffusion coefficient defines rate of diffusion and will depend on variables such as size of the molecule and viscosity of the boundary layer. A – the surface area and h the thickness of the boundary layer. And of course, a term to define the concentration gradient Cs – C. This term simplifies if dissolution occurs in sink conditions – which means if as soon as the dissolved drug moves into bulk solution it becomes absorbed and leaves the area then C is always close to zero and unchanged so Cs – C is in facto only Cs.

Answer 28

Saturated solubility Sink conditions Diffusion Boundary layer Viscosity

Answer 29

So let's think about this dissolution rate equation. We now know what all the terms mean. How are we going to make it work for us is called the Noyes Whitney equation, as I mentioned. So we can have an increase in dissolution rate. How could we do that? We can increase the dissolution rate, if we increase the surface area as we can grind our powder down even more, right? Which we can do. So can clearly do that. We can increase the diffusion coefficient. g. So e.g. we could reduce the viscosity of the liquid that it's in. Maybe we could increase the solubility in the first place. We can do all this stuff we said we would do in the last lecture, co solvents, all that other stuff you could do that may increase the solubility. We can decrease the boundary layer thickness, which you could do actually by messing about with flow rate of your liquid.

Answer 30

Concentration in bulk solvent effects Decrease concentration in bulk increases dissolution rate In GI fluid, concentration in bulk usually low as drug clears from the solution by partitioning through membrane But, if lots of drug dumped into GI fluid, concentration in bulk solvent can slow dissolution When testing in vitro, usually keep C < 10%Cs termed sink conditions- Typically use large volume dissolution media Transcript So I want to go through each of those terms. So a CS minus and C, right? Which is the concentration and bulk solution and that maximum concentration. If we increase the solubility, we're going to increase dissolution rate. And just to remind you, this is all come up in a previous lecture. We could do that with things like temperature. Yeah, we could do it by thinking about the pH, salt, everything we spoke about before, molecular structure. And then other components such as co solvents and adding solubilization agents and things like that. These are the things that we could do that would alter the solubility.

Answer 31

Diffusion is net movement of particles (in this case molecules) from an area of high concentration to low concentration Rate of diffusion is governed by the diffusion coefficient (D), which is dependent on the variables of temperature and particle (molecular) size – as is shown by the Stokes-Einstein equation D is proportional to temperature D is inversely proportional to size and viscosity Boundary layer is a static or slow-moving layer of liquid surrounding all wetted solid surfaces Thickness depends on viscosity and flow of solution over the solid High viscosity, slow flow rate = thick boundary layer So it inhibits movement of solute going from solid to bulk solution

Answer 32

An oral drug must be able to: Dissolve Survive a range of pHs (1.5 to 8.0) survive intestinal bacteria cross membranes survive liver metabolism avoid active transport to bile avoid excretion by kidneys partition into target organ avoid partition into undesired places (e.g. brain, foetus)

Answer 33

Okay, so let's start by thinking about that pH variation. So here's some pH of different fluids that you might have to come in contact with depending on what the administration route is for the drug. And so you can see here that within the gastrointestinal tract, e.g. if you're taking a medicine on a fasting stomach, you're starting with saliva at about 6.4, then going into the stomach it should be about 1.4 and then going through into the small intestine which is about 6.5. So there's a huge variation. We've also mentioned that drugs tends to be weak acids and bases, which means that the ionization state will change as they go through those different environments. We've also talked about how if the ionization state changes, the solubility changes. Yes. So if you have a more ionized drug, then it will be more soluble in aqueous environment compared to a non ionized drug. Okay? So we need to think about how we could measure and understand that process. So the important things here is that the charged form is more soluble in aqueous environment and it's less soluble in oil environment and vice versa for the non charged form. And of course, if it's going to cross a membrane, its got to have solubility in both of those environments.

Answer 34

Now, for a weak acid, you're going from the acid (HA, so the hydrogen is bound to the acid) And then that's an equilibrium with those two in ion form. And we can have an equilibrium constant because we know how to work out the equilibrium constant. So it's the concentration of the products over the concentration of the reactants. Now for a base, our ionized form is on the left side and the nonionized form of the base is on the right side. Okay? So it's the other way round for the base compared to the acid. So when we lose the hydrogen for the base, then we end up with the non-ionized form. So in that case, the product is the nonionized form of the base. So Ka gives us the proportion of products over the proportion of reactants at equilibrium. And if the two are equal, then we have obviously the same amount in both. The pH at which we have the two equal is our PKA, okay? It's when our drug is 50 per cent ionised.

Answer 35

the Henderson-Hasselbach equation. And you'll notice that it will switch around un-ionized on the top for the acid and ionized on the top for the base. And that's just basically because as the equations you saw a moment ago, for one, the product who was unionized, for the other, the product is ionised. Now if you have, let's look at that weak acid sample example. So the PKA equals the pH of log unionised over ionised. Now if the un-ionized and the ionized concentration of the same, that'll be 1/1. Okay? that ratio will be one. And so the log of one will basically be nothing. So the PKA will equal the pH. So we know that the pKa equals the pH when we have the same amount of unionized form of the weak acid compared to ionized form. So what we can do is we can work out that ratio for any pH if we know the PKA. Because you've got PKA. Its is just rearranging that the concentration of unionized form over the ionized form. We know the PKA, we know the PH that we are working at, we can work out these ratio of unionized, ionized quite easily. So that's why this equation is useful. You could think about the equations of different ways depending whether it's a weak acid or a weak base. In terms of whether the ionized and un-ionized go on the top or the bottom of that ratio Remember low pH means high H+ ion concentration and thus the molecule will retain its H (and be unionized if acid). On the other had a weak base would gain a H at low pH due to high hydrogen ion concentration and thus become ionized –NH3+

Answer 36

if it is more ionised, it means that it will be more soluble in water and so that means it's also less lipophilic. So lipophilicity is basically fat liking and it's important because it tells us how much the drug likes to go across a membrane, likes to go into the hydrophobic region of the membrane, right? Because the middle of a membrane is made up of lipids, right? And they're hydrophobic. And then it's got to cross that. It has to like going into the membrane. And then be happy to cross that in order to get anywhere, right? So lipophilicity is important. So we focus for making a drug and formulating it on how water-soluble it is. But if it is water soluble, then it will stay in solution. They won't want to cross the membrane. It's not gonna be any good. So that leads us to this idea that we have to also think about the lipophilicity of our drug. And it's important for absorption, for the distribution around the body, how quickly it will be eliminated from the body. So at all stages, the lipophilicity of the drug is important and how well it binds through active site as well. So that's why there's a huge list of things here you'll hear people talk about how lipophilic is your drug when they're talking about any of these sorts of actions here.

Answer 37

To consider the importance of lipohilicity it is important to understand hydrophobic interactions or the hydrophobic effect. This is an entropically drive process. If we try to mix something very non-polar with water, we create energetically unfavourable ordered and more rigid structures in terms of the movement of the hydrophobic moity and the solvent that surrounds or cages it. Entropy driven (remember ΔG = ΔH – TΔS). Hydrophobic molecules are encouraged to associate with each other in water. - Placing a non-polar surface into water disturbs network of water-water hydrogen bonds. This causes a reorientation of the network of hydrogen bonds to give fewer, but stronger, water-water H-bonds close to the nonpolar surface. Water molecules close to a non-polar surface consequently exhibit much greater orientational ordering and hence lower entropy than bulk water.

Answer 38

If a material is too lipophilic, we know it will be happy to leave an aqueous environment and cross into the lipid region of the biological membrane for absorption, but if too lipophilic it will not not be soluble enough to have at high enough concentrations in solution in the first place On the other hand, if a molecule is very hydrophilic it will be so happy in the aqueous environment it will not partition into the lipid region of the membrane and this is hinder absorption We need a balance. we use log P as our term to let us know if a molecule has that balance. If a compound is too lipophilic, right? It's hydrophobic. It won't dissolve in the aqueous environment in the first place. Which means it can't cross any membranes because it's not going to dissolve there in the first place. Okay. It'll bind too strongly to other things that we don't want it to bind to. So it won't be free. It won't be free and individual molecule in order to have any action at all. However, if our drug is to polar, as I've just said, is not going to cross that membrane. So we end up with this compromise, right? We need our drug to be lipophilic to a certain extent, it needs to be hydrophilic to a certain extent in order to allow it to cross the membrane. And sometimes that will depend on the pH. Might be that goes across the membrane much easier in certain pH compared to others. Which again links to the GI tract, right? Well, we have these range of different pHs. Maybe it crosses a membrane better in one area within the GI tract compared to another. Okay? Right, so lipophilicity we measure that. We use log P.

Answer 39

By convention, scientists use log P, because the P values can be quite large For example, estradiol P = 204 (204 molecules in octanol for every 1 in water) log Poct/water = 2.31 if P=106 Log P=6 if P=10-6 Log P=-6 if P=1 Log P=0 Maybe the next one, partition coefficients, okay? If you remember, I showed you this diagram here where you basically have a membrane between the two. Okay, so where will the drug ends up? In the oil phase or the water phase? And then you basically have the partition coefficient, which is our equilibrium constant. It's the concentration that ends up in the octanol phase over the concentration ends up in the aqueous phase, right? So if the partition coefficient is a number above one, then you can see that the drug prefers the octanol phase. And if the partition coefficient is a number below one, right? You can see it's going to prefer the aqueous phase. The partition coefficient is always going to be positive. The log of p, Will be positive when it's above one, and it'll be negative when the partition coefficient is under 1. So we use log P instead of P. I think the reason for that is because if you use P on its own, the values can get really, really large. So you can have it 1,000 times liking the oil phase more than water phase. And just because it likes the oil phase, 1,000 times more than it likes the aqueous phase isn't necessarily a problem- Still likes both, right? But obviously that would mean p is 1,000 or you could have p is ten size and 100,000. The numbers get big and weird. Which is why we use the log, right? Because if you've got a p, which equals 1,000 thousand times, basically it's 1000/1, right? Log will make it smaller. And then you can look up for any drug, you should be able to look up what the log P value is. All right? With that, you can predict how it will behave in different environments and how it will behave in multiple different ways that you might want to use it like we're going to use it to predict them in the workshop. Can predict how they might behave in terms of absorption across the membrane.

Answer 40

So as I said, log p is important and if you increase log P, remember by increasing log P, you're making it, the molecule is becoming more lipophilic. Then you can see that that has an effect on many different biological activities. We focus mainly and entirely in these lectures on solubility and absorption. But just giving you a few more examples there, where log P is an important parameter.

Answer 41

Simplistic explanation for absorption process Unionised form passes membranes Ionised form does not We have a concept known as the pH partition hypothesis. Log p is important. If your drug is a weak acid or a weak base, basically, it's log P changes depending on the pH. The hydrophilicty and its lipophilicity changes. If you have a weak acid and you have the PKA of your drug in the middle were 50% ionized and 50% and un-ionized, as you lower the pH, the drug becomes more un-ionized, which means it becomes more lipophilic. So it's going to absorb easier across the membrane as long as it's still soluble. And if you go to higher pH, above the PKA, then the drug becomes more ionized. So more aqueous solubility, but less ability to cross the membrane to absorb. Now obviously if you go beyond two pH units either side then you are either 100% non-ionized or 100% ionized. And it's the opposite for a weak base. So with PKA, if you go to lower pH, becomes more water-soluble, and if you go to higher pH, its better able to absorb across the membrane because it has better lipophilicity. So that is known as the pH partition hypothesis. That a theory, the absorption and the likelihood of it being able to absorb across the membrane, or how easy it will find it to absorb will be linked to pH and PKA in this way.

Answer 42

If you have a weakly acidic drug, so PKA of say three, then in the stomach with a pH of 1.2, it will be mostly ionized, 98.4%. In the intestinal fluids at pH of 6.8, it will be totally ionized. So in the stomach it's un-ionized, but in the intestinal fluids it's totally ionized. And for a weakly basic drugs say we the PKA of five, then at the stomach at 1.2, it's going to be pretty much all ionized. In the intestinal fluid, a pH of 6.8, it will be nearly totally unionised. Its solubility and lipophilicity has changed quite a lot as you go through the gastrointestinal tract, for those two examples there. Now, in the weak base case: it's, totally un-ionized in the intestinal fluid. So that means it's going to be more lipophilic and it's been more likely to be able to cross a membrane. The surface area of the small intestine is massive. Couple that with the fact that this is now slightly more lipophilic, it's going to cross that membrane very well. For the weak acid: now looks like it's going to favourably absorbed in the stomach because it's mostly un-ionized in the stomach. It will still be able to cross the membrane in the intestinal fluid, as long as it has some lipophilicity because of the huge surface area of the intestine. The pH partition hypothesis in this case, though, states that the weakly acidic drug is likely to be absorbed from the stomach where it's unionized. And that's true. Whereas conversely is a base unionized and absorbed in the intestine. So that just says where they prefer to be absorbed. I've already mentioned the impact of surface area here, because obviously the surface area in the intestine is significantly greater than the surface area in the stomach.

Answer 43

an example question. This is a drug. This is the structure of it. It has a PKA of five. So first of all, is it basic, acidic or neutral? Let's just say it's not gonna be neutral right, otherwise we wouldn't be putting it into this question. So is it a weak base or weak acid? It is a weak base. And then if you know it's a weak base, we can calculate the percentage ionization at different pH, using our equation for weak base. And then based on your calculation from that and what we know about lipophilicity, you could say where you think loratadine is more likely to absorb, in the stomach or the intestine? So it's basically taking those pH numbers, working out the percentage ionization in those two different states. So that's the example. This example, the answer to it is on Blackboard

Answer 44

1. No more than 5 hydrogen bond donors (the total number of nitrogen–hydrogen and oxygen–hydrogen bonds) 2. No more than 10 hydrogen bond acceptors (all nitrogen or oxygen atoms) 3. A molecular mass less than 500 Daltons 4. An octanol-water partition coefficient (log P) that does not exceed 5

Answer 45

A colligative property is when the thing that you're measuring changes with concentration of the solutes, but does not depend on the chemical structure of the solute. Examples there: vapor pressure, boiling point, melting point, osmotic pressure. These are things where if you change the solute concentration, you will see a change. It really doesn't matter what the solute is

Answer 46

Osmosis * Some substances form semipermeable membranes, allowing some smaller particles to pass through, but blocking other larger particles. * In biological systems, most semipermeable membranes allow waterto pass through, but solutes are not freeto do so. Osmotic pressure - It's the minimum pressure which you need to apply in order to prevent the flow of water from an area of high concentration of water to an area of low concentration of water. So, it is the pressure you need to apply to stop osmosis. So there's an example here where you've got your semi permeable membrane. If you add something to one side, then you've changed the concentration of water on that side, and so water will cross that membrane to account for that. That's known as that process is osmosis. So what pressure would you have to add to the system in order to stop the water from doing that. We tend to add salts or sugars in order to make something have the same osmotic pressure inside and outside of a cell. Osmotic pressure depends on the salt

Answer 47

if a solution therefore is iso-osmotic, okay? It means two solutions have the same osmotic potential. And if they're separated by a perfect semi-permeable membrane, you'll get no net movement. So this is ideal. Say if you give an intramuscular injection and you put enough of the drug into that side - what you don't want is for your body to identify that there's not enough water in the injection, right? And therefore, water goes in. And what do you get? You get swelling. Not really ideal. If you make it so that it is iso-osmotic to the surrounding tissue, so when you add it, It's not going to have that effect that may cause the patient pain. So it's really important that we get that right. We call this isotonic, right? if we're talking about biology, which we always are in the case of pharmaceutics, then we call iso-osmotic, basically isotonic. And the reason why we give it a different name is because biology isn't perfect, right? The membranes are not perfect two membranes. So that's why it's given slightly different terminology. So if two iso-osmotic solutions remain in osmotic equilibrium when separated by a biologic biological membrane, we would call that isotonic, just to differentiate between a non-perfect, non ideal system that you get in biology compared to these perfect lab systems there was the original definition for iso-osmotic.

Answer 48

So you know what happens when it comes to osmosis and how changing salt concentration will lead to either water going in, water going out. If you get the salt concentration right, then you would have neither a net effect of water going in or going out, it will be equilibrium. And then that is iso-osmotic/ isotonic for us, okay? Either extreme is hypertonic or hypotonic in biology. Both of them are pretty horrible. We've seen here with the red blood cells that if you go to hypotonic- water's coming out and with squishing them. If we go the other way, we're blowing them up. Both are bad. If we get it right, then we have this isotonic environment where the equilibrium in terms of the way the water goes is the same going into the cell as it's coming out of the cell. So we end up with the cell saying the right shape. Now remember, these are equilibrium processes, right? When you've got an isotonic, it doesn't mean nothing is going, doesn't mean it's static. It's fluid. Water is going in and water is coming out. It is just at this equal rate, both ways. They're both going equally fast. They haven't suddenly stopped. So solutions have the potential to cause water to move as we can see.

Answer 49

if we think about that from the point of drug administration, which is quite a sensible thing to do in these lectures. So let's start by thinking of subcutaneous injection. Usually for small volume, isotonicity isn't as important, but if it's a bigger volume than I would make it isotonic. And also it will give you less pain at the site of injection. Intramuscular really should be isotonic. For intravenous must be isotonic. Eye drops -probably ideal to have it isotonic, but because of the amount of tears the eye has, it will dilute the system anyway. Nasal drops very often or usually isotonic. So those are examples where the solution has to have the right sugar or salt. So sodium chloride, There's a defined concentration of sodium chloride that we use in order to make sure we have the isotonicity. It is about the concentration of the solute, not what the solute is. And it's called a colligative property

Answer 50

* A mixture in which very small particles of one substance are distributed evenly throughout another substance * Dimensions 1-1000 nm – can’t be seen by optical microscopy (remember dimension!!). If the particles are smaller tham * Colloids scatter light – Tyndall effect, even if they look clear * Large surface area (almost entirely surface rather than bulk) * Examples of colloids – fog and milk

Answer 51

- If we shine through a solution instead of a colloidal system – we wont see anything unless the molecules are very big which is not often the case - Colloid – particles are between 1-1000nm so we cannot see them so it will look like a clear solution OR will look cloudy. - But they are big enough to scatter light - Suspensions are different to colloids because the particles are bigger than 1000nm (this is known as course suspension) – we will be able to see them with the human eye, and the particles can scatter light - We are going to first focus on colloidal system

Answer 52

Lyophilic colloids - the colloidal solution in which the dispersed phase or the particles have a very strong affinity with the liquid. Examples of lyophillic colloids are * Micellar solutions (association colloids) ON NEXT SLIDE. These form when you have surfactants in the solution * Macromolecular solutions (polymers in solution) * Solutions – form spontaneously as they readily disperse in continuous phase – In water, these are hydrophilic colloids – as they like water – In LYOPHOBIC solutions, we may need to add other things in for the colloids to be stable because they do not like the solvent

Answer 53

These colloids are formed by the grouping or self-association of the dispersed phase which is amphiphilic (e.g., surface-active agents = surfactants). These molecules exhibit both lyophilic and lyophobic properties. We will look at micellar solutions as an example of solvent-liking colloid

Answer 54

The term surfactant comes from the word surface active agent. They are amphiphilic molecules (have a hydrophobic and hydrophilic part) and are thus absorbed in the air-water interface. At the interface, they align themselves so that the hydrophobic part is in the air (because it wants to be away from water) and the hydrophilic part is in water (as it likes water). This will cause a decrease in surface or interfacial tensions. They stabilise the surface.

Answer 55

Surfactants are typically classified based on their polar head as the hydrophobic tails are often similar. If the head group has no charge, the surfactant is called non-ionic. If the head group has a negative or positive charge, it is called anionic or cationic, respectively. If it contains both positive and negative groups, then the surfactant is called zwitterionic.

Answer 56

Surfactant solutions exhibit a sharp change in their behaviour as a function of concentration. At the start, they are in the solution just as the diagram above. They are floating around. They are substances that allow oil and water to mix. They are emulsifiers. The head stays in the water and the tail goes into the oil. It stabilises them both. But, when you get to a particular concentration of these surfactants, they arrange themselves into micelles. A micelle is an aggregate of surfactant molecules dispersed in a liquid, forming a colloidal suspension (also known as associated colloidal system).

Answer 57

When you add surfactants to a liquid, they will not form micelle structures right away. When you reach the CMC (critical micellar concentration), that is when micelles start to form. This graph is showing what happens when you start adding surfactants to the liquid. Lots of things are observed when micelles start to form. Lots of behaviours start changing -Osmotic pressure levels off - we are not seeing a change in concentration of individual molecules after that point (because micelles are being formed) -Remember that osmotic pressure is dependent on concentration so individual molecules are not increasing in concentration - they are forming micelles -Surface tension - goes down as more surfactants get added to the surface but levels off after micelles start to form as micelles are not surface active (meaning they do not gather at the surface so there is less tension at the surface) -Molar conductivity: huge reduction at CMC -Turbidity - increases at CMC -Lots of physical changes happen, all evidence that micelles indeed form when the concentration of surfactants added reach the CMC (critical micelle concentration)

Answer 58

* The change in entropy (how ordered something is) drives the formation of micelles. * Formation is an ORDERING process * Micelles disorder a system – this is desired. Keeping things organised takes time and effort. Having disorder is the default * When you have micelles, the micelle molecules are surrounded by water – the whole structure is all very rigid – disorder created * Micellization apparently involved ‘ordering’ process so why is S > 0 (Entropy BIGGER than 0 means it is disordered. If micelles make something more ordered, then why is the value bigger than 0 when ordering should make it smaller than 0? Answer: – Hydrophobic interactions - ‘tails’ in micelle very mobile – Solvent is less ordered – micelles make the solvent less ordered

Answer 59

Hydrophobic parts have to interact with water but they can’t because there is nothing polar Water cages around water Structured water – not ordered – disorder created Behaviour of water drives this affect -Change in entropy - drives formation of micelles -Formation of micelles is a disordering process -We are putting disorder into the system -Entropy drives formation of micelles because it LIKES disorder so prefers these micelles being made

Answer 60

The principle factor affecting cmc is the length of the hydrocarbon (hydrophobic) tail (i.e. the longer hydrophobic chain, the lower the cmc – less surfactant concentration is needed to trigger micelles). This is because the tail is insoluble and so the drive to make micelles is greater. When tails are short, might be okay with staying in the water as the hydrophobic part is small and therefore the drive to form micelles will be less because they are happy as they are. *For ionic surfactants another factor - a second factor in determining CMC is the nature of the head group - charge and of the counter ions *For non-ionic surfactants - length of hydrophilic head group: More significant for non-ionics (non-charged) - the head groups are all negatively charged so are all repelling each other and definitely want to make micelles. Adding even a little bit of those non-ionic surfactants will want them to form micelles even more

Answer 61

* Non-ionic head group: – lower cmc and larger aggregation number compared to ionic surfactants (i.e more molecules per micelle) – head group size increase (more hydrophilic) leads to cmc increase (e.g. PEO head group) * Ionic: – micellar size is affected by counter-ion Basically, When there is no charges on micelle heads, they can pack together tightly as there is no repulsion. Lots can come together without problems Charged micelles wont aggregate in huge numbers due to repulsion

Answer 62

* Temperature – more pronounced for non-ionics * Addition of simple electrolytes (to ionic micelles) – decreases cmc * Addition of organic molecules – can increase or decrease cmc

Answer 63

Reduces CMC - Critical micelle concentrations for sodium dodecyl sulphate in aqueous NaCl solutions at 25 oC * For ionic surfactants an increase in electrolyte concentration reduces repulsion between charged groups by screening * The salt is positive: it will reduce impact of negative charge * Micelles form more easily * Micelles are bigger aswell because more can pack together – the negative charge is giving less impact * If the headgroup is NOT charged, this whole thing wont make a massive difference. Effect overall will be less * Micelle formation is favoured and the cmc is reduced – micelles formed quicker

Answer 64

* Adding sugars – hydrogen bonds with water well. Interacts with water well. If you have water and sugar already bonded and when you now add hydrophobic head – water even more upset, so drive to form micelles higher – CMC decreases. * Urea – do not hydrogen bond, reduce concentration of hydrogen bonding in system, break water structure, allow water to be happy, CMC increases, micelles form less easily.

Answer 65

* Surfactant structure: * length of the hydrophobic tail (lower cmc) * For non-ionics - length of hydrophilic head group (higher cmc) * For ionic surfactants - the nature of the head group charge and of the counter ions (eg adding salt will lower cmc) * Solution conditions: * Temperature * Addition of simple electrolytes (to ionic micelles) decreases cmc * Addition of organic molecules (structure maker/breaker will lower/increase cmc)

Answer 66

Micelle size * Non-ionic micelles (detergents) contain ~ 1000 molecules * Ionic molecules contain fewer molecules (ca 10-100) due to electrostatic repulsions * Total size depends mostly on the length of hydrophobic tail Micelle shape: * Open to discussion - could be spherical, laminar, cylindical, vesicular * Typically: – Spherical for wide concentration range – low viscosity – Often transitions to liquid crystal structures at high concentration – high viscosity * Experimental evidence for spherical structure – cmc depends almost entirely on hydrophobic part – Micelles are approximately monodisperse (particles are same size) – Size depends on hydrophobic part – Ability to ‘solubilise’

Answer 67

- Slide is not linked to a particle in a solution or suspension - It is a micellar structure - We need to think about where we can put a drug - Left diagram: - Ionic surfactant. You can see positive charges associated with head group from the solution - Region around the micelle – stern layer (solution particles are strongly associated with it - Middle – hydrophobic core - Palisade layer – water and hydrophilic part of the molecule, both mixed together. It is the polymer and the water both - In the middle of this one too, hydrophobic core

Answer 68

Solubilization is the increase in solubility of a poorly water-soluble substance with surface-active agents. The mechanism involves entrapment (adsorbed or dissolved) of molecules in micelles - Solubilisates in core increase size of micelle and aggregation number to compensate swollen core - Solubilisates in palisade layer do not alter aggregation number but there is an increase in size

Answer 69

Maximum additive concentration - max amount of drug that can be incorporated (with the surfactant, compared to the amount of drug without it) *Micellar solutions can affect drug activity and protect drug against hydrolysis as drug is very stable in there - could be bad. Might not break down efficiently etc

Answer 70

- Phospholipid bilayer formed – central hydrophobic region where headgroups are - This is a vesicle - Also known as liposome - Very stable when formed - A lot of research going on in them - Put the drug in the middle

Answer 71

* Anionic surfactants (mainly as cleaners) – Sodium Lauryl Sulphate – preoperative skin cleaner/medicated shampoos * Cationic surfactants (mainly as cleaners) – Cetrimide BP is bactericidal –wound cleaning, storage of sterilised instruments, emulsifying agent * Non-ionic surfactants (main ones; large variety) – Amphiphilic nature often expressed using HLB – e.g. Sorbitan esters (Span), Polysorbates (Tween), Poloxamers

Answer 72

Hydrophillic/lipophilic number (HLB) - Hydrophilic/ lipophilic balance - Using the properties on the previous slide - Big hydrophobic portion – different HLB value - HLB tells you how hydrophobic something is or hydrophilic - Middle – both water and lipid soluble

Answer 73

*Sol (suspension) – dispersion of a solid in a liquid (or solid in a solid) *Aerosol – dispersion of a liquid in a gas *Emulsion – dispersion of a liquid in a liquid *Foam – dispersion of a gas in a liquid

Answer 74

Lyophobic means solvent hating -When you add oil to water, it wont just form an emulsion straight away. You need to add something to the mixture so that all the droplets don’t come together and join up again which they will. This means its unstable. The oil and water will not stay dispersed. It will layer up -You need to give it kinetic stability -It will stay dispersed for as long as we need it to when stability is given -For a suspension, that’s why you must shake the bottle before use -Shaking will make it re-disperse even if it separates out -Why not make it into a solution? Because the active ingredient might not be able to dissolve i.e. water soluble. Also because we can mask the taste in suspensions so work better in medicines like calpol

Answer 75

When you add one phase into another, you need to encourage it to suspend. -Think about the size. Smaller the particle size, the better stable it will be. -Make them as uniform as possible – two methods: dispersion method (grind the particles and make them small as possible) or condensation method– make a really concentrated solution and then do something so it crashes out of the system. Then little crystals can be made – grow the particles into suitable sizes -Once we have our particles, we must stabilise them -Particles will sink -Need them to float around and not sink

Answer 76

*Dispersion methods (by far the most common) –Colloid mills (by far the most common) –Ultrasonic treatment *Condensation methods –Rapid production of supersaturated solutions –e.g. change in solvent, cooling, chemical reaction (controlled rate of condensation -> controlled particle size)

Answer 77

* Measurement of kinetic properties enables molecular weight/particle size to be determined Thermal motions (brownian, diffusion, osmosis – depends on concentration but not on chemical species. For a given solvent the osmotic pressure depends only upon the molar concentration of solute but does not depend on its nature. Gravity (sedimentation) – stronger force than gravity needed for sedimentation – centrifuge – sedimentation velocity or sedimentation equilibrium related to molecular weight. Viscous flow (rheology) Viscosity – resistance to flow of a system under an applied stress – more viscous, the particles are bigger Sedimentation: Stronger force than gravity is needed for small particles to sediment Ultracentrifuge - Sedimentation velocity – rate of sedimentation under centrifugal force depends on size

Answer 78

* Light scattering – colloids scatter light (Tyndall effect) – Calculate size and shape from light scattering measurements as a function of scattering angle and concentration * Electron microscopy – Provides pictures of particles too small to be seen by optical microscopy

Answer 79

Most surfaces acquire a surface electric charge when brought into contact with a polar medium * The charge influences the distribution of ions – Ions of opposite charge (counter-ions) are attracted – Ions of like charge (co-ions) are repelled – An electric double layer is formed * What is the distribution of counter and co-ions within the interfacial region?

Answer 80

Charged surface May contain chemical groups that can ionise or enable adsorption of ions Surface charge determines many of the properties of the colloid, including providing kinetic stability. Diffuse region - Debye length Notes -positive charged particle -Some negative charged particles will adsorb to its surface -Other negatively charged particles will start associating with it -Electric double layer -Multiple layer of ions -Cloud of ions associated with the initial particle -Designed to counteract with the charge of particle -Start off with lots of negative ions -The further you go from the surface, the less the association -This idea is key to how we stabilise the suspension

Answer 81

Colloidal dispersions are thermodynamically unstable -Tendency to aggregate *Stability determined by interactions between particles -Kinetic stability - large energy barrier to aggregation -Short range repulsive interactions sufficient to prevent aggregation- electrostatic or steric

Answer 82

Stability depends on the TWO forces of interaction between dispersed particles *Repulsive forces: Electrical Double layer or steric repulsion *Attractive forces: Van der Waals (dispersion) forces (less important are Osmotic (steric) forces and Solvation forces) The DVLO theory explains this further

Answer 83

Total interaction = total attractive energy + repulsive energy -Black dots are the molecules that make up the particle -The green charges balance out the surface charge -Attractive interactions - all about the actual particle and whats it made of -Repulsion - all about surface charges

Answer 84

Stability of hydrophobic sols is treated in terms of the energy changes which take place as the particles approach There are different distance dependencies of attractive and repulsive forces -Attractive forces - blue lines -Repulsive - red lines -As particles get closer together, the attractive forces get stronger and repulsive decrease: this is the blue one -That's why we must add the forces together -Equals the black line -Remember the curve -Start from right - as the particles come closer together. You first reach the secondary minimum (flocculation). This is when the particles are starting to associate with each other but they are not close to each other yet. They are attracted to each other. As you try and bring them closer, there is a big repulsive barrier that tries to stop them getting closer. -If the system has enough energy that overcomes this barrier, they will come closer together and get into the primary minimum stage which is called coagulation. They will be stuck really close together - nothing will separate them -Relying on the energy barrier to stop them coagulating. Keep the barrier big (orange arrow) -If its flocculated, its loosely associated - it will move apart when shaken.

Answer 85

Aggregation -General term defining grouping of particles *Flocculation (secondary minimum) -Secondary minimum -This term is used if the aggregate is readily re dispersed. *Coagulation (primary minimum) -Primary minimum -This term is used if the aggregate is stable -Wont disperse again

Answer 86

Repulsive interaction between colloids, VR (summary) * For hydrophobic particles – London dispersion forces – Vary 1/x6 for the molecules * For an assembly of molecules (colloidal particle) – Sum of all molecular interactions – Result of summation is that the energy between colloidal particles decays less rapidly with distance than for individual molecules Repulsive interaction, Vr The repulsive interactions depend on: *Surface charge - as charge increases, the repulsive interactions increase *Concentration of ions in solution - increased concentration, lead to increased k, but reduced thickness of the double layer => repulsive interaction decrease

Answer 87

* Surface charge – as charge increases, the repulsive interactions increase * Concentration of ions in solution - increased concentration, lead to increased , but reduced thickness of the double layer => repulsive interaction decrease

Answer 88

According to DLVO theory, stability of a colloidal dispersion can be determined from total interaction energy, VT = VA + VR *VA depends on Van de Waals interactions (particle size and Hamaker constant) *VR depends on surface charge and diffuse layer thickness (electrolyte/ion concentration) or steric repulsion between hydrated surfaces

Answer 89

Stability of hydrophobic sols is treated in terms of the energy changes which take place as the particles approach There are different distance dependencies of attractive and repulsive forces * Stability of hydrophobic sols is treated in terms of the energy changes which take place as the particles approach * There are different distance dependencies of attractive and repulsive forces

Answer 90

Coarse suspensions - dispersed phase > 1 mm (Bigger than 1 micron (1000nm) *Applies to all these two-phase systems are 'coarse' if the disperse phase dimensions are > colloidal: -Suspensions -Emulsions -Foams -Aerosols

Answer 91

*Oral delivery -Children's paracetamol suspensions *Topical administration -Calmine lotion -Zinc cream - suspending powdered drug in an emulsion *Parenteral use -Controls rate of release of drug by varying size of dispersed medium -Vaccine formulations - prolongs antigenic stimulation

Answer 92

Pharmaceutical suspensions are often coarse suspensions – dispersed phase > 1 mm –Suspension should not settle too rapidly or too slowly –Should be readily dispersed on shaking –Should not be too viscous *Factors to consider in formulation –Sedimentation (gravity will play a part) can happen. They can coagulate at bottom if particles are too heavy –Electrokinetic properties – DLVO theory

Answer 93

Governed by: –Particle size – so reduce by mortar & pestle –Density of vehicle – so increase by adding polyethylene glycol, glycerin, sorbitol, sugar… –Viscosity of solution – so increase by adding suspending agents, e.g. methyl cellulose, acacia… –(More viscous means more thicker so make it thicker so the particles don’t fall through quicker

Answer 94

*Even a dispersion defined as stable will eventually sediment over time if particles are coarse –leads to ‘cake’ or ‘clay’ formation- stuck at bottom *Flocculation – secondary minima – particles sediment entrapping continuous phase and remaining discrete. Not stuck together

Answer 95

Avoid caked systems *Controlled flocculation –DLVO theory – produce system with a suitably deep secondary minimum, e.g. add electrolyte. Reduces thickness of diffuse layer *Steric stabilisation –Depends on both thickness and concentration of adsorbed polymer – also will effect Hamaker constant. Thus you can control it with polymers. You can let the polymer stick to surface of particle – can affect the attractive and repulsive forces –Need attractive forces to lead to flocculation and prevent close approach of particles (Graph 1 ) Stability of hydrophobic sols is treated in terms of the energy changes which take place as the particles approach There are different distance dependencies of attractive and repulsive forces (Graph 2 ) - Stability of hydrophobic sols is treated in terms of the energy changes which take place as the particles approach There are different distance dependencies of attractive and repulsive forces Ideally, repulsive forces will be bigger in colloidal system Dotted line – what it was before Red line – increased repulsive force Less easier for flocculation to occur Perfect for colloidal system – repelled further away which is great This is not ideal if the particles are BIGGER than colloidal This is because although the coarse particles would stay away from each other, they would sediment separately and they will cake at the bottom. Adding an electrolyte to reduce that repulsive interaction

Answer 96

Stability of hydrophobic sols is treated in terms of the energy changes which take place as the particles approach There are different distance dependencies of attractive and repulsive forces

Answer 97

-Adding electrolyte reduces the diffuse layer that surrounds surface of particle -Adding too much - reduce the repulsive forces too much and you get coagulation -A CCC -amount of electrolyte that you have to add to a system to get it to aggregate in some way -Sometimes you just have to add a bit of electrolyte

Answer 98

Electrolyte is a salt Will have a positive and negative ion Surface of particle is also negative or positive If surface is positive, then counter ion will be negative and vice versa If the counter ion is 1+ or 2+ etc then it will influence the flocculation Hardy Schulze rule states that the amount of electrolyte required for the coagulation of a definite amount of a colloidal solution is dependent on the valency of the coagulating ion. Coagulating ion is the ion which has the charge opposite to the charge of the colloidal particles

Answer 99

Added ions of opposite charge to colloid act as flocculating agents *Efficiency of flocculation increases with ionic charge ..... Useful for diagnoses of particle charge - find out what charge it is *Charge number of co-ions has no effect on CCC (Critical coagulation concentration)

Answer 100

-Need to think about charge of POSITIVE ion we add - as it is a negative surface (AS2S3) -The positive ion in red is already +1. You need the same amount to force this system to aggregate -Blue - all already +2. So you need less positive charge added in order for you to aggregate the system -Green - all already +3 - need even less positive charge to make it aggregate. About 10 folds smaller -The only thing that is changing the ability of coagulation is the positive ion in the salt

Answer 101

Evaluate suspension – determine physical stability – Look at sedimentation volume very big means lots of solvent is trapped in that so more likely to disperse when you shake it. Helps you figure out how much it will flocculate –Degree of flocculation *Packaging –Wide mouthed container with air space –Protect from freezing, heating, light –Label ‘shake before use’

Answer 102

Dispersion of one liquid into another *Many similarities to suspensions (solid into liquid) but also show other characteristics (e.g. coalescence of liquid droplets =turn into bigger droplets, they merge *As for suspensions, most emulsion are kinetically (artificially stable) rather than thermodynamically (naturally) stabilised *Given time the liquids will separate into two phases (break) so must add something to emulsion to make it more stable. Only stay stable for a set amount of time *Have very limited shelf life

Answer 103

Coalescence state is a problem Size of droplet matters If they flocculate but NOT coalescence - that is creaming Milk - emulsion, really well mix

Answer 104

*Oil in water (o/w); water in oil (w/o) *Multiple emulsions (e.g. o/w/o) *Render oily substances (liquid paraffin) more palatable *Used to formulate together oil- and water-soluble drugs *Topical preparations *Administration of oils and fats by intravenous infusion - parenteral nutrition programme

Answer 105

Interfaces are where two phases meet. They can meet in lots of different ways. You can think of an interface between the air and this solid surface here. That's an interface, right? So if things adsorbed to that or stick to it, that's an interfacial interaction that's occurring there between air and the surface of a droplet. Between the droplet of water interacting with oil would be an interface. Then we have also liquid and solid. So how something interacts to the surface of the container. So perhaps how a medicine that you're storing is interacting to the surface of the container before it's given to you or a patient. And also within the body we have interfaces. The smaller a particle becomes, for instance, in a system as we showed yesterday or last week: If you have a big block or something and we're talking about solubility here – the smaller the particles, the more quickly it will dissolve.

Answer 106

- Focus on the interface between air and water - Water has high surface tension - Which means you can float things on it like paper clips etc, even insects can float on it - You couldn’t float that on alcohol or detergent etc - Because surface tension has been lowered - We will talk about water surface tension in a moment - If you add anything to water, it will lower water surface tension

Answer 107

Short range forces of interaction exist between molecules Molecules within bulk of liquid are subjected to equal forces of attraction in all directions Interfacial molecules experience unbalanced attractive forces and are attracted inwards Water droplets are spherical * Short range attractive forces of interaction are responsible for existence of liquid state * Interfacial molecules – unbalanced (asymetric) attractive forces – net inward pull surface tension (surface will tend to contract eg. Spherical bubbles) – as many molecules as possible will leave surface for the interior of liquid (In other words surface molecules have excess energy and liquid has minimum energy when minimum surface area)

Answer 108

* Here we have water molecules * They interact very strongly with each other * Cohesive forces exist between water molecules (non covalent interactions as they can hydrogen) * This means at the surface, the molecules at the surface are very different energetically to the ones in the middle of the water. * Middle ones – very balanced forces. Acting in all directions, can interact with lots of other water molecules * Net effect- low energy * But the ones at the surface – they can interact with water molecules on the side and down but NOT up since none exist at the top above them * The net force is down * They cant interact with anything above * If the force of interaction is very high between water molecules, so the net force down is very high * Surface tension of water is therefore very high because strong cohesive forces between water molecules is high * Unbalanced forces for the surface is high – therefore we have an inward pull * Surface tension is therefore the force acting to minimise the surface area. * You can add things to water to disrupt the surface tension but water itself has very high surface tension

Answer 109

Surface tension and surface free energy are dimensionally equivalent and numerically equal. Surface tension is the same as surface free energy. Unblanaced forces at the surfaces that leads to a net inward force of attraction that pulls molecules down – surface tension Contraction of surface that leads to a minimum free energy state as we are minimising the number of molecules that will be at the surface You can think about this concept from a free energy point of view, work point of view or surface area point of view

Answer 110

Interfacial tension – surface tension between two immiscible liquid phases. Usually interfacial tension lies between surface tensions of each liquid. - Water is unique - If you put water on hydrophobic surface, it will be a whole droplet on the surface that can roll off easily. - Water has surface tension of 72 - Units of surface tension are millinewtons per meter - When water is interacting with air, it has surface tension that’s very high - All the other ones are lower as you can see - Interfacial tension is surface tension but tends to be a way of defining surface tension when between 2 liquids that are immiscible (cannot mix) rather than that liquid with air. - If it is a liquid and air interface, we will call it surface tension from now on - If it is a surface tension between oil and water for example, we will call it interfacial tension - Water – air interface – 72 (very high), lots of cohesive interactions, lots of hydrogen bonding - Octanol and air – ST of 27. Obviously, here we have van der waals forces interacting here, we don’t have strong polar and strong electrostatic interactions here, no strong hydrogen bonding either. Thus the net pull down at surface is less therefore the ST is less. - Same for chloroform, olive oil and N-hexane - We can relate ST to how strong the intermolecular forces between the molecules of that liquid are - All depends on the net pull down - When you look at the IT between water and all these liquids, as they are all immiscible with water, then you can see that it will change depending on how well that liquid can interact with water - Octanol – IT with water is low as octanol has OH in the molecule so will be slightly less dense. - Don’t get that strong pull at the surface - They interact well together at the surface - They will like being at the interface anyway because they wont have to deal with the OHs in the middle which is a mostly quiet and oily environment. - Interfaces between chloroform, olive oil and n-hexane – a lot more tension therefore the numbers are higher

Answer 111

- Get the plate which is very thin - Link it to something that can measure weight - Put it so that it has contact with the surface of the liquid - As you try to pull it out, the liquid will hold it in depending on how strong the liquid can hold it in (this is surface tension) - It measures how much the liquid can pull it down - Simple way of measuring surface tension - Force acting on the plate is due to water wetting the plate – so it depends on how good the water wets the plate - Easy way of measuring surface tension

Answer 112

- Another way of measuring ST - Think about bubble - Liquid can create bubbles - Some pressure exists at surface of bubble - Air bubble in water, or any water bubble present - We have something pushing it down - Surface tension is pushing it down, trying to make the surface area be small - Also have pressure inside it - This will happen at any curved surface - Pressure difference inside and outside the bubble exists - The concave side, concave side exists – pressure on concave side (inside) is greater than pressure on convex side - That’s why when you put a capillary tube inside a beaker of water, that water inside the narrow capillary tube will be higher than the water in the beaker and this is due to surface tension – it is pulling all the way up the tube to reduce water tension.

Answer 113

Surface tension acts on the convex side trying to flatten the surface and minimise the surface area. If the liquid wets the surface of the capillary then adhesion to the wall will be favoured to the liquid will rise up the tube. - Another way to measure surface tension - Put a capillary tube in a liquid - Liquid will rise up capillary tube - Amount it rises is proportional to the surface tension * Capillary action is a tendency of liquids to rise up capillary tubes – a consequence of surface tension The movement of a liquid up and down a capillary tube is related to surface tension

Answer 114

Surface tension never significantly increases A substance that tends to increase  of a liquid will also raise surface free energy and so concentrates less at the surface Decreases in surface tension A dissolved substance that lowers surface tension also lowers the surface free energy and so tends to migrate towards the surface resulting in a large depression in  What sort of molecules would decrease surface tension? Which would i expect to be higher water or ethanol? Why is water high? - If you have water and add something to it, It will get harder to balance things on the liquid - When something dissolves in a liquid, it reduces ST - Because energetically we know that molecules tend to show cohesiveness – it is that cohesiveness that is pulling it down - Dissolving things will reduce the cohesiveness - Cant add anything to water to increase its tension

Answer 115

* Surface active agents occur widely in nature and have been used for over 1000 years as emulsifiers in cleaning and in foods. * They are molecules composed of two distinct regions – A polar (hydrophilic) moiety termed the head group – A nonploar (hydrophobic) moiety termed the tail. – The headgroup ensures water solubility whilst the tail drives the formation of self assembled aggregates or colloidal structures. Surface activity. A strong tendency for molecules to orientate at an interface to form a monomolecular layer (monolayer) Surfactants adsorb such that the ‘head’ is in the aqueous phase and ‘tail’ in the hydrophobic phase - known as amphiphilic molecules For example, short chain fatty acids and alcohols are soluble in both water and oil. Adsorption is energetically more favourable than being in solution in either phase same as the driving forces for micellisation – hydrophobic interactions A surfactants tendency for an interface favours expansion of that interface and reduces surface tension - Add these to reduce the surface tension - Like adding a detergent – it will make the floating item sink - This thing you are adding is doing something at the interface - It’s a surface acting agent or a surfactant - Occur widely in nature - Many different types i.e. food things, cleaning products, hair products etc - They mess around with interfaces - What does the surfactant do? Reduces surface tension of course. - Has hydrocarbon tail - Has hydrophilic head group - Hydrophillic part can interact with water – very happy - The hydrophobic head will not. It hates water. Water will cage around it, cant interact, water wants to throw it out. This is a big problem - They will line up in order to try to minmise the amount of tail that has to interact with water - It can line up at the interface neatly - Molecules prefer to be at interface - Tails are in air – very happy as they are away from the water - The pull down on surface is no longer there - We have more forces at the surface than we’ve had before - Surface tension goes down - Surfactants always go to surface

Answer 116

* A surfactant’s tendency for an interface favours expansion of that interface and reduces surface tension * Surfactants adsorb at interfaces to form a layer one molecule thick - a molecular monolayer * That’s how they line up * Monolayer – packs tightly like that * Align very well * Adsorption is energetically more favourable than that molecule being in bold solution

Answer 117

* Anionic – SDS sodium dodecyl sulphate: used in a wide range of cleaning and hydene products; used in DNA extraction and protein identification (SDS-page) * Cationic – CTAB (cetronium bromide is a component of a topical antiseptic cetrimide * Non-ionic – C12E5: PEG head and alkyl chain * Amphoteric (zwitterionic) – CHAPS: use to solubilise proteins and as a non-denaturing solvent for protein and membrane protein purification. * Can be classified in this way * Anionic and cationic – most often in cleaning * Non – ionic – internal and external use * Zwitterionic – in nature, most common charge on a phospholipid head group

Answer 118

increase in hydrophobic chain length leads to increase in surface activity in a homologous series ‘in dilute aqueous solutions of surfactants belonging to any one homologous series, the molar concentrations required to produce equal lowering of surface tension of water decreases threefold for each additional CH2 group in the hydrocarbon chain of the solute’ - Surfactant reduces surface tension - Traubes rule can measure by how much - Surfactant series – is where head group is the same but has multiple lengths of the tails (any carbon long) - No simpler way of putting it - If you want to reduce surface tension, you want to add the minimum amount possible

Answer 119

increase in hydrophobic chain length leads to increase in surface activity in a homologous series ‘in dilute aqueous solutions of surfactants belonging to any one homologous series, the molar concentrations required to produce equal lowering of surface tension of water decreases threefold for each additional CH2 group in the hydrocarbon chain of the solute’ A C16 chain molar concentration of 8 x 10-3 M gives a surface tension of 35 mN/m; what concentration of a C14 chain would be required to produce a similar surface tension: C14 has 2 less CH2 groups so 8 x 10-3 (x3 x3) = 72 x 10-3 M.

Answer 120

Lots of drugs are Amphiphillic Substitution affects surface activity– such as Br on Bromopheniramine which lowers CMC and surface tension - Ampiphillic means a molecule that has a hydrophobic part to it a hydrophilic part - If the hydrophobic part can go to the surface in any way and reduce the surface tension, then it will - Their hydrophobic part is more complex than this sort of standard hydrocarbon chain that they’ve shown

Answer 121

Surfactants (detergents) also help clean the teeth, and provide a foam that helps to carry away debris. Moreover, lauryl sulfates have significant anti-bacterial properties, and they can penetrate and dissolve plaque. Lauryl sulfates can irritate oral membranes, and so a similar detergent, lauryl sarcosinate often replaces some or all of the lauryl sulfate. Allantoin is sometimes added to relieve the irritation caused by detergents, alkalies, and acids. - wetting: adding oil to water for example, will not work and oil does not mix with water. If you add a surfactant to it, it will help the liquid to wet this surface. Then nature takes over – wants to be at the interface itself. It will remove the dirt away from the surface - Emulsification: when you have water droplets and oil droplets don’t want to mix – two phases want to separate out. Adding a surfactant, it will coatthe droplets, help it to have lots of interfaces - Lubricant – for similar reasons - Can be used to reduce static as it goes to surfaces - Use things to disperse things - Used in foaming antifoaming and foaming aswell

Answer 122

* Surface active agents occur widely in nature and have been used for over 1000 years as emulsifiers in cleaning and in foods. * They are molecules composed of two distinct regions – A polar (hydrophilic) moiety termed the head group – A nonploar (hydrophobic) moiety termed the tail. – The headgroup ensures water solubility whilst the tail drives the formation of self assembled aggregates or colloidal structures. Surface activity. A strong tendency for molecules to orientate at an interface to form a monomolecular layer (monolayer) Surfactants adsorb such that the ‘head’ is in the aqueous phase and ‘tail’ in the hydrophobic phase - known as amphiphilic molecules For example, short chain fatty acids and alcohols are soluble in both water and oil. Adsorption is energetically more favourable than being in solution in either phase same as the driving forces for micellisation – hydrophobic interactions A surfactants tendency for an interface favours expansion of that interface and reduces surface tension * Making hydrophobic tails longer – means that more of the molecule hates water so drive needed to get it out is greater

Answer 123

Above a certain concentration (the critical micelle concentration), aggregates of 20 or more molecules, called micelles form. There is a rapid and continuous exchange of monomers within the micelle with bulk solution meaning that the micelle itself is a very disordered, mobile aggregate Micelles have a reasonably large but finite lifetime ca. 10-2 – 10 s - At low concentrations, that’s exactly how they behave as individual molecules. They adsorb at surfaces aswell or exist inside the solution - If you get to higher concentrations, there are a lot of them in solution - They are tightly packed at the surface – but the ones inside the solution don’t want to be there either. Their hydrophobic tails do not like the water - They start aggregating and form these structures called micelles - Hydrophobic world is in the middle and heads are on the outside – happy - Micelle is happy to live in water - Concentration is called critical micelle concentration (CMC) - Remember, EXCESS molecules make micelles. At the start, all the molecules went to the surface and started decreasing the surface tension. When the MAXIMUM molecules are at the surface, the surface tension cannot be decreased further - When MORE molecules are added, they do not go to the surface as surface is packed already so they will start forming micelles which wont reduce the surface tension further as they are NOT going to the surface. So surface tension after the CMC stays the same.

Answer 124

Hydrophobic interactions  Basically an entropic interaction  Responsible for micellisation of surfactants and oily inner phase of folded protein

Answer 125

Below CMC – adsorption increases with concentration leading to reduction in surface tension Above CMC - concentration of surfactant monomers in solution remains constant. Micelles are not surface active so surface tension remains constant

Answer 126

Enables the extent of adsorption at a liquid surface to be estimated from surface tension data Surface excess () is adsorbed amount: i=ni/A (units: mol m-2) where ni is number of moles and A is surface area Gibbs Adsorption equation - Surface tension linked to amount of material at surface - Number of moles at surface area - Beyond the cmc, this doesn’t work as number of molecules at surfaces does not change - Only use it for curved part - Don’t use it for straight part after cmc

Answer 127

R is gas constant T is temperature For a surface tension curve of  vs lnC, surface excesses can be determined from the tangents of that curve since d/dlnC = - RT B * Units of surface excess: mol/m2 If surface excess tells you e.g. there are 6 molecules in a defined space You can easily work out how much area molecule needs at the surface Defined space divided by number of molecules

Answer 128

* Surface excess is able to be measured from our surface tension against ln concentration graph from the gradient. Surface excess is the number of moles per unit area - so per metre2 * area per molecule is the reciprocal of surface excess – so 1/surface excess – the area each molecule has at the surface * In this example here, the surface excess is high – the molecules are packed together as tightly as possible – the number of moles within each m2 will be relatively high. The space that each molecule has is as small as physically possible – and this is the area per molecule. In fact the area will now reality to the size of the molecule – the smallest space it can occupy at the surface – making it a useful term. * because we measure this as per molecule and surface excess is in moles we also divide surface excess by Avogadro's number to do from moles to molecules.

Answer 129

* Amphiphilic molecules with long hydrocarbon chains – form insoluble monomolecular films * o surface tension of clean interface (water);  surface tension with monolayer;  is surface pressure * Know amount at interface by knowledge of amount added (using suitable solvent) and area of water surface * 2D states analogous to normal 3D states of gas, liquid and solid and depend on lateral adhesive forces * Factors such as ionisation (pH of substrate) and temperature play an important part in determining the nature of the film * Long chain fatty acid – not soluble in water * These are surfactants * If you have a really big hydrophobic – they will remain on top of the water * Can be used to reduce evaporation of water

Answer 130

The physical states of monomolecular films Condensed (solid) film – molecules are closely packed Expanded film – films are coherent but occupy larger area than condensed films (act as highly compressible liquids Gaseous (vapour) films – molecules are separate and move about surface independently * Measure  as a function of of area/molecule (which is known as know volume of of applied solution) * Gaseous – no cohesion forces between molecules (if charged then a repulsive force) - * Condensed – cohesion between hydrocarbon chains keeps molecules together at high film areas – surface pressure remains low – on compression pressure rises rapidly * You can have different results based on how the molecules behave * Green – surface area pressure increases quickly. That’s because these particular molecules (gaseous), they stay separate from each other for as long as they possibly can * No cohesive interaction, especially when they come close to each other, they don’t like it, they stay away. When you bring the space together, eventually they have to align because theres no space for them but they will do that at the last minute Condesnsed – molecules stick together, strong cohesive interaction, act like solid, as you compress, feels like nothing is happening. When you get to a point where they are very compressed and very small area per molecule, suddenly you will see a drop in surface pressure. This is because these types of molecules align and stick together Expanded monolayer – in the middle, some solid behaviour some gaseous properties

Answer 131

* Myristic acid – more than one well-defined transition between geseous and coherent states are observed as film is compressed * Physical state depends on lateral cohesive forces between molecules variations in chain length, straight chain fatty acids, temp, head group size and charge lead to various monolayer states. * Note EVAPORATION THROUGH MONOLAYERS – coating a water surface with insoluble monolayer can reduce water loss by up to 40% (in hot countries lakes and reservoirs lose 3m of water due to evaporation (without monolayer) * Oxygen can diffuse readily through monolayer – monolayers have been used successfully for this purpose

Answer 132

- At the start, spread out (gaseous behaviour) - Suddenly changes its behaviour, suddenly the molecules flip up and stand up (phase transition) - Now they are happy to pack tightly as so are acting like condensed films

Answer 133

- You can see that if you add a droplet at the surface, you can find out a lot about the surface - Droplet may sit high or low i.e. rough surface will make droplet sit more spread out - Depending on how hydrophobic is, will determine how high droplet will sit – more higher - Angle can tell you how hydrophobic surface it - Surfactant can improve wettability – how good something is wetted. Adding detergent makes saucepan better wetted - Glass surface – very hydrophilic so water spreads more

Answer 134

NOT ABSORPTION – absorption implies penetration; adsorption is just at surface - Two terms sound very similar - Easy to use these terms in the wrong place - Absorption – INTO the surface - Adsorption – just on surface - Adsopbate – the solute that’s binding to surface - Adsorbent – the surface

Answer 135

Hads c.a. -10 kJ/mol Hads c.a. -100 kJ/mol - Two different types – physical and chemical - Physical – binding that does not involve covalent interaction, read off the slide - All reversible, mobile and multilayered - Favoured by low temps - Weak, non covalent interactions - Chemisorption – strong covalent bond - Wont move unless another chemical reaction - Only monolayer - Very localized

Answer 136

Define adsorption isotherm – there are 3 Concentration vs time How coverage changes with concentration Type 1: increases and levels off because it’s a monolayer so cannot increase in concentration when the entire monolayer is full. Isotherm – measured at a single temperature Type 2: monolayer formed first, then multilayer forms Type 3: don’t get monolayer formed first. Still multilayer

Answer 137

A process that is irreversible Involves a covalent bond involves weak non covalent interactions is not able to form multilayers

Answer 138

At iep, solubility minimum and adsorption maximum Increase in temperature results in increase in solubility Surface - If surface is very hydrophobic, more reason for the molecule to try and get water away from surface and try to bind at surface itself - Hydrophobicity of surface increases, adsorption increases - Looking at surface and adsorbate interaction - If you put a manmade material in contact with the body like catheter, first of all you will get adsorption of small proteins like albumin etc - Do get cases of adsorption which will lead to clots etc (uncontrollable adsorption) - Temperature – read off slide

Answer 139

In general, detergents are made up of surfactants and ‘builders’ ‘builders’ (e.g. silicates, pyrophosphates) are not surface active Act as deflocculating agents or alkaline agents Optical brighteners are also added - Dirt stuck - Surfactant adsorbs onto surface - Hydrophobic bits stick onto surface - surface free energy reduces - Dirt lifts up - Surfactant surrounds dirt – sees more surface and binds onto all surface of dirt - micelles encapsulate the dirt - Rinse it – dirt cannot reattach

PM1b Spring Term - T/E/S/I Flashcards

(173 cards)