Pharmaceutical Materials Flashcards
(39 cards)
What do the properties of solid drug materials depend on? (2 factors)
- Their chemical composition.
This includes the arrangement, type and ratio of atoms that make up a drug formulation - The solid structure of the drug and excipients and how they interact with each other
What are examples of different solid forms of the same drug?
A drug can exist in its hydrate, anhydrate, polymorphous, amorphous, solvate and salt form
What happens when you change the solid form of a drug?
Stability of the drug is altered
Bioavailabilty is altered
Manufacturing and processing factors have to be adapted
Explain bioavailability
It is the percentage of the dose of a drug that is systemically circulated.
When the solid form is changed of a drug, bioavaliability is altered and therefore the dose may also have to be altered
What are the rate limiting steps of hydrophobic and hydrophilic drugs?
The rate limiting step for hydrophobic drugs is dissolution rate whereas for hydrophilic drugs absorption across the GI tract is the rate limiting step (phospholipid bilayer)
How is the manufacturing process affected by different solid formulations?
Different solid forms have different chemical properties forming different shapes, different brittleness and therefore compression processes have to be adapted accordingly.
What is the difference between a particle and a molecule?
A molecule is comprised of atoms held together in a covalent bond.
A particle is comprised of millions of molecules held together by non covalent bonds such as hydrogen or van der waals forces.
Are amorphous materials completely disordered?
No, although amorphous materials have no repeating cell unit, their local structure is not random. (For example black molecule attached to four white molecules).
What are the two ways molecules in a particle can be arranged?
Molecules can be arranged in a crystalline structure or amorphous.
Crystalline materials are comprised of a unit cell (small portion of crystal lattice) which is repeated in three dimensions.
Amorphous materials do not have a long range repeating order but locally they do.
What are the most common crystal systems?
Crystal systems that occur the most in drugs are triclinic, monoclinic or orthorhombic.
Triclinic- all three axis unequal in length and none are perpendicular to each other
Monoclinic- all three axis unequal in length and two are perpendicular to each other
Orthorhombic- all three axis unequal in length and all are perpendicular to each other
Crystal systems correspond to the shape of the unit cell
What is polymorphism?
It refers to two different crystalline versions of the same compound. So the crystalline structure exhibits two different crystal systems.
Paracetamol for example can be found in the monoclinic and orthorhombic form.
Do two polymorphous forms exhibit the same properties?
They have different melting points and solubilities due to the different arrangement of molecules and therefore the strength of interactions differ.
Once dissolved/melted the product is the same. It doesn’t matter which crystal system is used.
The rate of reaction would differ as well as the concentration of the drug in equilibrium with the saturated solution.
How can you can distinguish which polymorph is the most stable?
The polymorph with the lowest free energy will be the most stable at a given temperature and pressure.
However the other form is known as being metastable. Eventually the metastable version will convert to the stable version but sometimes the kinetic barrier is so high it can survive as the metastable form for years and is known as being kinetically stable.
Will one polymorph form always be more stable?
If two polymorphs are in a monotropic relationship, one polymorph will always be more stable than the other regardless of temperature.
However if they are in a enantiotropic relationship the more stable form is dependent on the temeperature. There is a conversion temperature in which the more stable form changes. (Gibbs free energy of one increases more drastically than the other).
Is it easy to tell whether you have the stable polymorph form of a drug?
No, because metastable forms take years to convert to the stable form so it is hard to predict what form is being manufactured.
As long as a pharmaceutical company can ensure that the product shelf life of a drug is shorter than the time is would take to convert to another polymorphous form then it is safe.
How does bioavailability reflect the stability of polymorphous forms.
The more stable form of a drug has stronger interactions between its molecules therefore requires more energy to overcome, has a slower dissolution rate (must be in solution to be absorbed across the GI tract), therefore a lower bioavalibilty and a bigger dose would be required to match the concentration of the metastable form.
What does supersaturation mean?
The concentration is higher than the equilibrium solubility which is the thermodynamic driving force for growth of a crystal. It induce this, most drugs more soluble at higher temperatures so by cooling more of the drug is in solution.
If the concentration is lower then the solution is stable and a crystal won’t grow.
How could you supersaturate a hydrophobic drug?
Dissolve the drug in ethanol and then add water which decreases the solubility of the solution and crystallization begins.
What are the two types of nucleation?
Homogenous nucleation is where the nuclei of the crystal begins to form with other crystal particles.
Heterogeneous is where the nuclei of the crystal begins to form around foreign material which has interacted with the solution.
Why does nucleation require energy?
Nucleation or specifically the formation of nuclei requires energy as the solute-solvent interactions have to be broken in order for the crystal to begin to form.
The maxima energy point corresponds to the critical nuclei size, once this point is reached an energy input is no longer required and increasing the cluster is energetically favourable.
What is seeded crystallisation?
In pharmaceutical industry seeded crystallisation involves added either homogenous or heterogenous nuclei to drug molecules which enables them to diffuse to the surface and attach to the growing crystal nuclei.
What is crystal habit?
Crystal habit is the external shape of the crystal which differs from crystal system which is the internal shape of the crystal corresponding to the shape of the repeating unit cell.
Rate of crystal growth influences the crystal habit.
What are some examples of crystal habits?
Acicular (needle shape)- formed by fast crystal growth in one direction.
Platy ( planar Hexagon)- formed by slow crystal growth in the vertical axis, but fast in the surrounding directions.
What factors can influence crystal habit?
Cooling rate and increase in degree of supersaturation yields longer needles/thinner plates (the crystal habit becomes more extreme).
