Self Assessment questions for Surface Phenomena

Question 1

What is surface or interfacial tension and how is it measured? Describe the principle of the du Noüy tensiometer.

Answer 1

The force per unit length acting parallel to the surface or interface so as to counterbalance the net inward attraction

• Measured by ring method and capillary rise method (only for surface tension and not interfacial tension)
• du Noüy tensiometer: measures the force to detach a platinum ring from a surface or an interface ( see attached image for formula)

Question 2

Use examples to highlight the importance of surface phenomena to pharmacy.

Answer 2

• Adsorption of drugs onto solid adjuncts in dosage forms
• Penetration of molecules through biological membranes
• Emulsion formation and stability
• Dispersion of insoluble particles in liquid media to form suspensions

Question 3

How is interfacial tension formed and what affects interfacial tension?

Answer 3

• In the bulk of a liquid, molecules are subject to equal attraction in directions (cohesive force) –> results in unbalanced forces between molecules are the surface (contraction of surface) = SURFACE TENSION

> Temperature = increase in temperature leads to a decrease in surface tension for most of the liquids

Question 4

A) How does adsorption occur at liquid surfaces or interfaces?

B) What affects surfactant adsorption at the interface and why?

Answer 4

A)

Through monolayers (an adsorption layer which is one molecule thick, they exist in different physical states: solid, liquid or gas)

• Soluble monolayers (adsorbate is soluble in liquid)
• Insoluble monolayers or films (adsorbate is insoluble in the liquid but spreads on the surface of liquid to form a film)

B)

• Reduction of surface/interfacial tension (some water molecules at surface/interface are replaced by non-polar groups of surfactants and attraction forces are reduced as its not between two water molecules anymore)
• Micelle formation (surface saturated with surfactant molecules –> additional surfactant molecules are forced into bulk –> to minimise free energy and protect lipohilic end from environment –> molecules cluster together to form micelles with lipophilic ends orientaed to inside of micelle)

Question 5

What effects do surfactants have on the interfacial tension and why?

Answer 5

• As the concentration of surfactant molecules increases at surface/interface layer, the surface/interfacial tension DECREASES

> this is is due to accumulation of added molecules at durface/interface which reduces free energy and surface tension by reduction of surface/interfacial tension and micelle formation

• Intermolecular forces between surfactant and water molecule are much lower than between two water molecules
• As surface layer becomes saturated with surfactant, no more surfactant concentration will change surface tension so now micelles form (at or above CMC) to shield non-polar groups in aqueous solution
• CMC = critical micelle concentration (conc of surfactant in a bulk phase)

Question 6

Describe surface excess

Answer 6

it is the amount of surfactant per unit area of surface in excess of that in the bulk of the liquid

Question 7

True or false questions (see attached image)

Answer 7

1) False
2) False
3) False
4) True
5) False
6) True
7) True
8) False

Question 8

What are the differences between a soluble and an insoluble monolayer?

Answer 8

Soluble monolayer: Surfactants

Insoluble monolayer: insoluble amphiphile (fatty acids) and polymeric materials (proteins and synthetic polymers)

• Soluble monolayers: adsorbate (added molecule) is soluble in the liquid
• Insoluble monolayers or films: adsorbate is insoluble in the liquid but spreads on the surface of liquid to form a film
• Soluble monolayers formation: Amphilic substances adsorb at interfaces and orientate themselves to keep the lipophilic group away from the aqueous environment thereby to achieve a minimum free energy state.
• Insoluble monolayers formation: Dissolve the substance in a suitable volatile solvent and carefully inject the solution on to the surface to form a film one molecule thick

Question 9

Explain the calculation of area per molecule and its application

Answer 9

What a dumb question

Ų < 30 therefore its a condensed film

Question 10

Explain surface pressure and the significance or application of surface pressure versus area per molecule

Answer 10

Surface pressure: difference in surface tension between the pure liquid and coated liquid –> Langmuir trough

• When graphed against area per molecule, can find out which type of monolayer is it (gaseous, liquid or condensed)
• As surface pressure increases, monolayer changes from gaseous -> liquid –> condensed (graph shows the opposite)

Question 11

Discuss different states of monolayers and their characteristics

Answer 11

See attached image

Question 12

Analyse adsorption phenomena in pharmacy and discuss cases where adsorption is desirable and cases where adsorption is undesirable.

Answer 12

Helpful when its adsorption and not negative adsorption –> added molecules migrate away from surface to bulk and increase free energy and surface tension

• Adsorption by the adsorbents present in medications such as antacids or in anti-diarrheal products that are taken at the same time
• Possibility of drug adsorption onto formulation ingredient such as kaolin or bentonite – reducing drug bioavailability
• Adsorption onto container walls - problematic with those highly surface-active and present in low conc (eg preservatives, protein and peptides –> insulin)

Question 13

Summarise the factors influencing adsorption at L/S interface.

Answer 13

• Solubility of adsorbate (effect is stronger than ionisation)

> Adsoprtion α 1/solubility

• Effect of pH on adsorbate

> Ionization : Adsorption is max when drug is completely unionized

> Amphoteric compound: a net charge zero –> maximum adsorption

• Nature of adsorbent

> Most important property: surface area

• Temperature

> Adsorption is generally an exothermic process

Question 14

What advice should you give to patients who are taking both antibiotics and antacids?

Answer 14

• Avoid taking them together if possible
• IF not, space dose between 2-3 hour intervals

Question 15

Discuss the causes and implications of protein adsorption

Answer 15

What causes it:

• Therapeutic proteins are extremely surface active
• Charge of surface is opposite to protein
• When surface is extremely hydrophobic
• When pH of the protein solution is equal to PI
• Using polystyrene or containers with silanyl or plasticizer ocatings

Implications;

> Loss of bioactivity of proteins due to surface-induced protein denaturation by processes:

• Irreversible adsorption
• Surface-associated aggregatio
• Precipitation of protein

Question 16

How can you prevent or minimise undesirable protein or drug adsorption?

Answer 16

Best defence: prevention of adsorption

• Use containers with smooth glass walls
• Avoid polysterene or containers with silanyl or plasticizer coatings
• Block access of proteins to the surface by including surfactants containing long ethylene oxide chains (CHAPS)
• Use of surfactants to reduce adsoprtion and aggregation
• Control pH to avoid pI

Question 17

Use examples to explain strategies you can use to either reduce or increase the adsorption of a solute from solution onto solid surfaces.

Answer 17

Reduce the adsorption of a solute from solution onto solid surfaces

• Use negative adsorption? (increases surface tension and free energy)
• Opposite of all the things below

Increase the adsorption of a solute from solution onto solid surfaces

• Make sure drug is completely unionised –> max adsorption
• Use amphoteric compound (net charge zero) –> max adsorption
• Decrease solubility of polymers (controlled by formation of hydrogen bonds with water) = increase adsorption
• The larger the surface area of the adsorbent, the greater the extent of adsorption
• Increase temperature = increase temperature

Question 18

Give examples of pharmaceutical applications of adsorption

Answer 18

• Separation ( eg HPLC, TLC analysis)
• Purification (water or protein purification)
• Removal of noxious substance (use of activated charcoal) –> SA important factor for its effectiveness
• Formulation of drug delivery systems
• Bioadhesive dosage form: wound healing, skin burn
• Adsorption of hydrophilic polymer at o/w interface- emulsifier

Question 19

True or false questions (see attached image)

Answer 19

1) False
2) False (for monolayer study only)
3) True
4) True
5) False
6) True
7) False

Question 20

Describe the basis for the classification of surfactants

Answer 20

Classified by anionic, cationic, non-ionic and ampholytic (hydrophilic portion)

Question 21

Discuss the factors determining the surface activities of surfactants. Explain the process of micelle formation

Answer 21

Dependent on balance between hydrophilic and hydrophobic properties;

• Increased hydrophilicity = decreased surface activity
• Increase in length of ethylene oxide chain of non-ionic surfactant leads to an increase in both surface tension and the CMC

Process of micelle formation;

• Micelles form after the surface (L/G interface) becomes saturated with soluble amphiphiles (surfactant)

Question 22

Explain why micelles form spontaneously at concentrations above the CMC

Answer 22

• Micelles form spontaneously because their formation is energetically favourable. ie forming a micelle leads to a system of lower free energy
• Lowered free energy by decreasing the contact between the hydrophobic groups of the surfactant and water, until the surfactant concentration reaches the CMC
• Before reaching the CMC, the surface tension decreases sharply with the concentration of the surfactant. After reaching the CMC, the surface tension stays more or less constant

Question 23

Which feature distinguishes micelles from all other colloidal particles?

Answer 23

Micelles form colloidal particles, they are hydrophobic and hydrophilic while colloidal particles and lyophilic and lyophobic??

Question 24

Explain a strategy to induce micelle formation at a concentration below the normal CMC value of an ionic surfactant.

Answer 24

• Add electrolytes

Question 25

What is HLB and its application? How do you calculate the HLB value for a mixture of surfactants?

Answer 25

Hydrophile-lipophile balance;

• A measure of relative contributions of hydrophilic and lipophilic regions of the molecule
• High value = hydrophilic
• Low value = lipophilic
• Arbitary scale (0-20) calculated using empirical formulae

Calculate HLB value for a mixture of surfactants;

• x HLB_A + (1-x) HLB_B (x: fraction of surfactant A) (1-x fraction of surfactant B)

Question 26

Explain the process of solubilisation by surfactants

Answer 26

• Water insoluble/partly soluble substances are brought into aqueous solution by incorporation into micelles
• Solubilisation only occurs when micelles are formed
• Concentration of surfactant must be > CMC
• Above CMC = amount of substance solubilized increases as the surfactant concentration increases (ie as the no of micelles increased)

Question 27

What is the disadvantage of using surfactants in solubilisation to increase solubility of poorly water soluble drugs?

Answer 27

Own potential toxicity (unsuitable for IV administration) and low achievable drug load

(not too sure)

Question 28

What factors influence solubilisation?

Answer 28

1. Nature of surfactant

> CH2 chain length; solubilisation increases with increase in alkyl chain length

> Ethylene oxide chain length; aggregation number decreases with increased chain length (micelle size decreases but total number of micelles increases)

2. Temperature

> Amount solubilised increases as temp increases (increase in micellar size with some non-ionic surfactant)

3. pH

> Alters equilibrium between ionised and unionised drug (affects drug solubility in water and modifies partitioning of drug between micellar and aqueous phase)

Question 29

What should be considered before using a surfactant as a solubilising agent or diluting a solution in which a drug is solubilised by surfactants?

Answer 29

• Conc. of surfactant must be maintained above CMC level (caution with dilution)
• Biological influence of surfactants on drug absorption and bioavailability

Question 30

True or false questions (see attached image)

Answer 30

1. False
2. True
3. False
4. False
5. False
6. True

Question 31

Identify various functions of surfactants in different dosage forms

Answer 31

• Dispersing drug powders in liquid vehicles
• Cotton pad and bandages

Question 32

Explain effects of surfactants on drug absorption in vivo

Answer 32

When surfactants are at low conc;

• disrupt cell membrane –> enhancing drug penetration and absoprtion of drug across GI barrier

When surfactants are above CMC level;

• For soluble drug: inhibition of absorption
• For poorly soluble drug: dissolution and absorption rates are increased

When surfactants are at high conc;

• increased amount required for solubilisation
• Decreasing chemical potential of drug
• Decreased drug absorption

When surfactants are included in formulation;

• Increase drug solubility

Question 33

What is a wetting agent ? Explain the mechanism by which a wetting agent can affect drug dissolution

Answer 33

Lowers contact angle between surface and wetting liquid

• Aids penetration of the liquid
• Reducing tendency of particle aggregation. effectively increases SA of solids exposed to fluids

Question 34

Describe the differences between a wetting agent and a solubilizing agent, particularly their effects on dissolution

Answer 34

Both surfactants

• Wetting agents increases the dissolution rate of a solid drug by aiding penetration of fluid and reducing the tendency of particle aggregation (increase SA of solids exposed to fluid)
• Solubilising agents increases disssolution rate of a drug (faster than wetting agent)

Differences

• Wetting agent lowers surface tension while solubilising agents dont
• Wetting agents dont alter solubility of a solid but solubilising agent may

Question 35

Discuss the functions of emulsifying agents

Answer 35

• Stabilise emulsions –> They form films at the interface between phases in an emulsion (protective layer) –> makes it mroe stable

Question 36

Identify the types of materials which can be used as emulsifying agents and the mechanisms by which they can stabilise an emulsion

Answer 36

Materials: Surfactants, hydrophilic colloids, solid particles

reduction of interfacial tension –> reduces surface free energy (surfactants)

provision of electrostatic repulsion –> if emulsifying agent is charged (HC with ionic group)

steric stabilisation –> prevents doplets from approaching each other

Some surfactants can also increased the viscocity of emulsions –> impede movement of droplets (HC)

Question 37

True or false questions (see attached image)

Answer 37

1. True
2. False
3. False
4. True
5. False
6. False
7. False
8. True
9. False