W1.2_Molecules and Materials

Question 1

Give out examples of molecular, material characteristics, and those that can be categorised into both. (5, 17, 3)

Answer 1

• Molecular: ionisation, solubility, pKa, polymerisation grade, chemical stability
• Material: melting/boiling points, particle size, surface area, absorption/adsorption, crystallinity, composition, chemical/physical purity, viscosity, physical stability, dissolution rate, crystal forms, microscopy, powder flow, compression
• Both: colour (based on electron cloud size/colour polymorphism), taste (principle/influence), excipient compatibility

Question 2

Explain how the characteristics impact the drug formulation of aspirin, omeprazole sodium, and alginic acid.

Answer 2

• Aspirin: weak acid, unionised in stomach pH -> move cross epithelium but slowly due to low solubility in chyme -> ionised in small intestine -> move across membranes slowly but absorbed rapidly due to large surface area
• Omeprazole sodium: weak base, omeprazole is highly ionised -> sodium salt form required to neutralise stomach acid -> eliminate need for protective coating, increase solubility
• Alginic acid: weak acid, unionised in stomach, can absorb large amount of water at low pH -> high viscosity -> form a physical barrier floating in gastric acid contents to reduce acid reflux into oesophagus

Question 3

Define interfacial phenomena, surface, and interface. Contrast the properties of surface and bulk materials by giving an example.

Answer 3

• Interfacial phenomena: different phases of immiscible liquids in contact
• Surface: outer boundary of a material/surrounding air
• Interface: boundary between two phases (S/L, L/V, S/V)
• Surface material properties are usually different from bulk material properties (ex. materials can be readily wetted but not dissolve in water, such as adding poorly soluble solid drug in water causes suspension)

Question 4

Describe the formation of surface tension. Define the force and explain how increasing temperature may affect it.

Answer 4

• Interaction between gas and liquid molecules are weaker than between liquid molecules (H-bonds)
• Imbalance of forces causes contracted surface in a state of tension (to achieve minimum surface area to volume ratio)
• Consequence of long-range interactions (H-bonds)
• Surface tension = force applied to resist external forces due to cohesive nature of water molecules
• Increasing temperature -> increase entropy -> reduce stability of H-bond network -> reduce surface tension

Question 5

Relate surface tension to formulation of emulsions, skin penetration of drugs, and formulation of solution.

Answer 5

• Emulsions have a large interfacial area between dispersed (small droplets) and continuous (surrounding liquid) phase -> surfactants/surface active agents are used to control/reduce surface tension
• Different parts of skin show different spreading/wetting -> chemical enhancers are used to reduce surface tension and improve penetration of drugs through skin
• Water: highest surface tension of all pharmaceutical liquids
• Addition of organic impurities reduces surface tension (ex. adding methanol will concentrate at air-water interface)

Question 6

How is surface tension measured?

Answer 6

• Liquid: function of polar and dispersion forces
• Most commonly used: microbalance based (ex. Wilhelmy plate/du Nouy ring to measure detachment force)
• ≈ Ratio of measured force when it detached over the perimeter of plate

Question 7

Which interface is the most important and why? Define wettability and immersional wetting.

Answer 7

• Majority of active pharmaceutical ingredients (API) are solids at room temperature -> API will be in contact with liquids during processing/formulation and in body fluids -> S/L interface is very important
• Wettability: assess the extent of a solid coming in contact with a liquid
• Immersional wetting: initial wetting process for a solid to be immersed in a liquid (effectiveness related to contact angle)

Question 8

What is the purpose of surfactants? Constrast the surface tension of liquids and solids.

Answer 8

• Surfactants: reduce surface tension of water -> coat drug to induce immersion/emulsion
• Liquids: molecules move freely -> consistent surface tension over whole surface
• Solids: held more rigidly, surface tension can be affected by crystallisation/milling (lead to different rough surfaces/spreading abilities) and orientation of crystal (as different chemical groups will be on the surface)

Question 9

Define and explain contact angle (θ). Describe how surface tension of hydrophobic drugs can be reduced.

Answer 9

• Contact angle (θ): used to determine interfacial tension of S/L interface indirectly as it’s not possible to measure forces exerted on surface
  -> Estimate tendency for liquid to spread
  -> Average value is used when drug crystals have different oriented faces
  Experiment determination is done by taking images (*tangent)
  -> θ<90 degrees: good spreading -> more contact, wettable (vice versa)
  Ex. hydrophobic drugs require wetting agents, such as surfactants, to lower surface tension between solid drug and vehicle to favour suspension of solid