Self Assessment questions for Surface Phenomena Flashcards
What is surface or interfacial tension and how is it measured? Describe the principle of the du Noüy tensiometer.
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)
Use examples to highlight the importance of surface phenomena to pharmacy.
- 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
How is interfacial tension formed and what affects interfacial tension?
- 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
A) How does adsorption occur at liquid surfaces or interfaces?
B) What affects surfactant adsorption at the interface and why?
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)
What effects do surfactants have on the interfacial tension and why?
- 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)
Describe surface excess
it is the amount of surfactant per unit area of surface in excess of that in the bulk of the liquid
True or false questions (see attached image)
1) False
2) False
3) False
4) True
5) False
6) True
7) True
8) False
What are the differences between a soluble and an insoluble monolayer?
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
Explain the calculation of area per molecule and its application
What a dumb question
Å2 < 30 therefore its a condensed film
Explain surface pressure and the significance or application of surface pressure versus area per molecule
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)
Discuss different states of monolayers and their characteristics
See attached image
Analyse adsorption phenomena in pharmacy and discuss cases where adsorption is desirable and cases where adsorption is undesirable.
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)
Summarise the factors influencing adsorption at L/S interface.
- 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
What advice should you give to patients who are taking both antibiotics and antacids?
- Avoid taking them together if possible
- IF not, space dose between 2-3 hour intervals
Discuss the causes and implications of protein adsorption
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
How can you prevent or minimise undesirable protein or drug adsorption?
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
Use examples to explain strategies you can use to either reduce or increase the adsorption of a solute from solution onto solid surfaces.
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
Give examples of pharmaceutical applications of adsorption
- 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
True or false questions (see attached image)
1) False
2) False (for monolayer study only)
3) True
4) True
5) False
6) True
7) False
Describe the basis for the classification of surfactants
Classified by anionic, cationic, non-ionic and ampholytic (hydrophilic portion)
Discuss the factors determining the surface activities of surfactants. Explain the process of micelle formation
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)
Explain why micelles form spontaneously at concentrations above the CMC
- 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
Which feature distinguishes micelles from all other colloidal particles?
Micelles form colloidal particles, they are hydrophobic and hydrophilic while colloidal particles and lyophilic and lyophobic??
Explain a strategy to induce micelle formation at a concentration below the normal CMC value of an ionic surfactant.
- Add electrolytes
What is HLB and its application? How do you calculate the HLB value for a mixture of surfactants?
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 HLBA + (1-x) HLBB (x: fraction of surfactant A) (1-x fraction of surfactant B)
Explain the process of solubilisation by surfactants
- 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)
What is the disadvantage of using surfactants in solubilisation to increase solubility of poorly water soluble drugs?
Own potential toxicity (unsuitable for IV administration) and low achievable drug load
(not too sure)
What factors influence solubilisation?
- 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)
- Temperature
> Amount solubilised increases as temp increases (increase in micellar size with some non-ionic surfactant)
- pH
> Alters equilibrium between ionised and unionised drug (affects drug solubility in water and modifies partitioning of drug between micellar and aqueous phase)
What should be considered before using a surfactant as a solubilising agent or diluting a solution in which a drug is solubilised by surfactants?
- Conc. of surfactant must be maintained above CMC level (caution with dilution)
- Biological influence of surfactants on drug absorption and bioavailability
True or false questions (see attached image)
- False
- True
- False
- False
- False
- True
Identify various functions of surfactants in different dosage forms
- Dispersing drug powders in liquid vehicles
- Cotton pad and bandages
Explain effects of surfactants on drug absorption in vivo
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
What is a wetting agent ? Explain the mechanism by which a wetting agent can affect drug dissolution
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
Describe the differences between a wetting agent and a solubilizing agent, particularly their effects on dissolution
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
Discuss the functions of emulsifying agents
- Stabilise emulsions –> They form films at the interface between phases in an emulsion (protective layer) –> makes it mroe stable
Identify the types of materials which can be used as emulsifying agents and the mechanisms by which they can stabilise an emulsion
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)
True or false questions (see attached image)
- True
- False
- False
- True
- False
- False
- False
- True
- False
