GPAT Physical Pharmacy Syllabus

What is the Tyndall effect and which colloidal property does it demonstrate?

The Tyndall effect is the scattering of a light beam by colloidal particles, making the beam visible. It demonstrates the optical property of colloids and distinguishes colloidal dispersions from true solutions.

What is the DLVO theory used to explain?

DLVO (Derjaguin-Landau-Verwey-Overbeek) theory explains the stability of lyophobic colloids/dispersions as the balance between attractive van der Waals forces and repulsive electrical double-layer forces; the net potential energy curve predicts coagulation or stability.

Define zeta potential and its significance in dispersion stability.

Zeta potential is the electric potential at the plane of shear (slipping plane) around a charged particle in a dispersion. Higher absolute zeta potential (>±30 mV) means greater repulsion and better stability against aggregation/flocculation.

State the Schulze-Hardy rule for coagulation of colloids.

The Schulze-Hardy rule states that the coagulating (flocculating) power of an electrolyte is determined by the valency of the ion opposite in charge to the colloid; the higher the valency, the greater the coagulating power (e.g., Al³⁺ > Ca²⁺ > Na⁺ for a negative sol).

Differentiate flocculated and deflocculated suspensions.

Flocculated: loose aggregates (flocs), rapid sedimentation, large loose sediment that redisperses easily (no cake), supernatant clear. Deflocculated: individual dispersed particles, slow sedimentation, dense hard cake that is hard to redisperse, supernatant cloudy.

Define sedimentation volume (F) and degree of flocculation (β).

Sedimentation volume F = Vu/Vo (volume of final sediment / original suspension volume); F = 1 is ideal. Degree of flocculation β = F/F∞ (sedimentation volume of flocculated / deflocculated suspension), expressing the increase due to flocculation.

What are the major types of emulsions and the methods to identify them?

Types: oil-in-water (o/w) and water-in-oil (w/o) (and multiple emulsions w/o/w, o/w/o). Identification: dilution test, dye solubility test (water-soluble dye colors o/w uniformly), conductivity test (o/w conducts), and fluorescence/filter paper tests.

List the main types of emulsion instability.

Creaming/sedimentation (reversible upward/downward migration), flocculation (reversible aggregation), coalescence/cracking/breaking (irreversible droplet fusion), and phase inversion (o/w changing to w/o or vice versa).

What is phase inversion in emulsions and what can cause it?

Phase inversion is the change of an emulsion from o/w to w/o (or vice versa). Causes include altering phase volume ratio (>~74% internal phase), adding an electrolyte/ion that changes emulsifier solubility, temperature change (phase inversion temperature), or changing the emulsifying agent type.

Define buffer and buffer capacity, and give the Van Slyke equation.

A buffer resists pH change on adding small amounts of acid/base. Buffer capacity (β) = ΔB/ΔpH (moles of acid/base per liter per unit pH change). Van Slyke: β = 2.303·C·[Ka·[H3O+]/(Ka + [H3O+])²], maximal when pH = pKa.

At what pH is buffer capacity maximum and what is its value relation?

Buffer capacity is maximum when pH = pKa (i.e., [salt] = [acid], buffer ratio = 1). At this point maximum β ≈ 0.576·C, where C is the total buffer concentration.

Define isotonicity and the methods used to adjust tonicity.

Isotonic solutions have the same osmotic pressure (and freezing point depression) as body fluids/blood (≈0.9% NaCl). Methods to adjust tonicity: freezing point depression method, sodium chloride equivalent (E value) method, White-Vincent method, and Sprowls method.

What is the sodium chloride equivalent (E value)?

The NaCl equivalent (E) is the weight of NaCl that produces the same osmotic effect as 1 g of the drug. It is used to calculate how much NaCl is needed to make a drug solution isotonic.

State the four colligative properties of solutions.

Vapor pressure lowering, boiling point elevation, freezing point depression, and osmotic pressure. They depend on the number of solute particles, not their identity.

State the van't Hoff equation for osmotic pressure.

π = (n/V)RT = cRT (for non-electrolytes), and π = icRT for electrolytes, where π = osmotic pressure, c = molar concentration, R = gas constant, T = absolute temperature, and i = van't Hoff factor (number of dissociated particles).

Define the van't Hoff factor (i).

The van't Hoff factor (i) is the ratio of the actual number of particles in solution after dissociation to the number of formula units initially dissolved. For non-electrolytes i = 1; for fully dissociating electrolytes it approaches the number of ions (e.g., NaCl ≈ 2).

State the Arrhenius equation and its logarithmic form.

k = A·e^(−Ea/RT); logarithmic form: log k = log A − Ea/(2.303·RT). k = rate constant, A = frequency/Arrhenius factor, Ea = activation energy, R = gas constant, T = absolute temperature. A plot of log k vs 1/T gives slope −Ea/2.303R.

Give the integrated rate equations and half-life for zero- and first-order reactions.

Zero-order: C = C0 − k0·t; t1/2 = C0/2k0 (half-life depends on concentration). First-order: log C = log C0 − kt/2.303; t1/2 = 0.693/k (half-life independent of concentration).

Define shelf life (t90) and give its expression for a first-order reaction.

Shelf life (t90) is the time for the drug to degrade to 90% of its original potency (10% loss). First-order: t90 = 0.105/k. Zero-order: t90 = 0.1·C0/k0.

What is the order of reaction versus molecularity?

Order is the experimentally determined sum of the powers of concentration terms in the rate law; it can be zero, fractional, or integer. Molecularity is the theoretical number of molecules taking part in an elementary reaction; it is always a whole positive number.

Differentiate pseudo-first-order kinetics from true first-order.

A pseudo-first-order reaction is actually second-order, but one reactant (e.g., water or a catalyst) is present in large excess so its concentration stays essentially constant, making the rate appear first-order with respect to the limiting reactant (e.g., ester hydrolysis).

List the main pathways of drug degradation.

Hydrolysis (esters/amides), oxidation (autoxidation/free-radical), photolysis (light-induced), reduction, racemization, decarboxylation, polymerization, and isomerization. Hydrolysis and oxidation are the most common.

What methods are used to stabilize drugs against oxidation?

Add antioxidants (e.g., BHA, BHT, ascorbic acid, sodium metabisulfite), use chelating agents (EDTA) to sequester metal catalysts, exclude oxygen (nitrogen purging), control pH, use amber/light-protective containers, and store at low temperature.

Define polymorphism and its pharmaceutical significance.

Polymorphism is the ability of a solid drug to exist in more than one crystalline form with the same chemical composition but different lattice arrangements. It affects solubility, dissolution rate, stability, melting point, and bioavailability (metastable forms dissolve faster).

Differentiate polymorphs, pseudopolymorphs (solvates/hydrates), and amorphous forms.

Polymorphs differ only in crystal packing of the same molecule. Pseudopolymorphs (solvates/hydrates) incorporate solvent/water molecules in the lattice. Amorphous forms lack long-range crystalline order, generally giving higher solubility/dissolution but lower stability.

State the Kelvin equation and its relevance (e.g., Ostwald ripening).

ln(p/p0) = 2γM/(rρRT) (or for solubility ln(s/s0) = 2γM/(rρRT)). It shows vapor pressure/solubility increases as particle/droplet radius r decreases; this drives Ostwald ripening, where small particles dissolve and large ones grow.

State the Henry's law for solubility of gases in liquids.

Henry's law: the mass (or mole fraction) of a gas dissolved in a given volume of liquid at constant temperature is directly proportional to the partial pressure of the gas above the liquid: C = k·P, where k is the Henry's law constant.

What are the techniques to enhance the solubility/dissolution of poorly soluble drugs?

Particle size reduction (micronization/nanonization), salt formation, pH adjustment, use of co-solvents, complexation (e.g., cyclodextrins), solid dispersions, micellar solubilization with surfactants, amorphous forms, and prodrug approach.

What is the diffusion layer (film) model of dissolution?

The diffusion layer model assumes a thin stagnant saturated liquid film (thickness h) forms at the solid surface; drug dissolves instantly into this layer at saturation concentration Cs, then diffuses across the film into the bulk, with diffusion being the rate-limiting step (basis of the Noyes-Whitney equation).