W10 Preformulation - Dissolution PDF

MPharm Programme Preformulation- Dissolution Prof. Amal Ali Elkordy Professor of Pharmaceutics E mail: [email protected] MPharm Preformulation- Dissolution  DRUG DISSOLUTION Overview What? Definitions of terms Why? The drug dissolution is i...

MPharm Programme Preformulation- Dissolution Prof. Amal Ali Elkordy Professor of Pharmaceutics E mail: [email protected] MPharm Preformulation- Dissolution  DRUG DISSOLUTION Overview What? Definitions of terms Why? The drug dissolution is important How? Drug dissolution can be measured MPharm Preformulation- Dissolution  DRUG DISSOLUTION State of matter: Solid, Liquid and Gas Melting: Solid heat Liquid Solubility: is the mass of the solute that dissolves in a specific mass or volume of a solvent at a given temperature (a static property Dissolution: is the process by which a solid drug substance becomes dissolved in a solvent (a dynamic property) MPharm Preformulation- Dissolution  varies MELTING for different materials of the bonds in the ↳ strengths different ~ crystal lattices are Melting point (m.p.): the temperature at which a solid changes to a liquid. Melting requires heat: Heat of fusion ( H) is the amount of heat absorbed or released as the system changes its thermodynamic state: For example: m.p. (ºC) H (cal/g) Aspirin 135 45.52 Palmitic acid 63 39.18 MPharm Preformulation- Dissolution  Why? Drug dissolution is important Most drugs need to dissolve first in the body fluid before their absorption (for example: drugs in capsules and tablets should dissolve in the gastrointestinal fluid), as shown in the following Model: MPharm Preformulation- Dissolution  Disintegration Deaggregation Drug in Granules or Solid drug dosage particles aggregates forms Dissolution Drug in Drug in blood, solution Absorption In vitro tissues /In vivo (In vivo) MPharm Preformulation- Dissolution Dissolution process: H will accompany dissolution of a solid in a solvent MPharm Preformulation- Dissolution Illustration of drug dissolution process Hess's law 1- On the molecular level heat of fusion for solute ↑ ↑ + +U = ss H, Step 1 in E is needed to previous heat of fusion Slide ! break these bonds > - endothermic for solvent ↑ + ULL = UHz Step 2 solute solvent bonds X like Isolute sheloa form + to ↓ interactiona ⑰O solvent > moleculesdissolving solid dre f - e j surrounded bu ↓ find heat of fusion molecules of solvent for solution - solvation ↑ -2 UsL = OHn Step 3 will be ~ E released one discrete solvated , Exothermic process: -2UsL > Uss+ULL entity > - once solute molecule diffuses the away from the surface of the Endothermic process: -2UsL < Uss+ULL solid into bulk solution dissolving ↳O 8 MPharm Preformulation- Dissolution Illustration of drug dissolution process 2- Simple diffusion model 37c body temperature (CS) Diffusion Aqueous layer phase (CB) Concentration Solid drug particles CB x=0 x=h x MPharm Preformulation- Dissolution  Illustration of drug dissolution process The Noyes-Whitney equation This equation describes the dissolution rate on the basis of the simple diffusion model (“film theory”) understand dC / dt k A(CS CB ) dC/dt= rate of drug dissolution k= dissolution rate constant= D/h D= diffusion coefficient h= thickness of diffusion layer (“film thickness”) A= surface area CS= saturation solubility of the drug CB= concentration of the drug in the bulk solution MPharm Preformulation- Dissolution  Illustration of drug dissolution process The Noyes-Whitney equation This equation describes the dissolution rate on the basis of the simple diffusion model (“film theory”) dC / dt k A(CS CB ) dC/dt= rate of drug dissolution k= dissolution rate constant= D/h D= diffusion coefficient h= thickness of diffusion layer (“film thickness”) A= surface area CS= saturation solubility of the drug CB= concentration of the drug in the bulk solution MPharm Preformulation- Dissolution  Illustration of drug dissolution process Factors affecting drug dissolution Agitation of the dissolution medium (solution) h= thickness of diffusion layer Viscosity of the solution D= diffusion coefficient Particle properties such as particle size, wetting of the particles and porosity A= surface area crystalline form of the drug CS= saturation solubility of the drug volume of the solution CB= concentration of the drug in the bulk Excipients (formulation factor) MPharm Preformulation- Dissolution How? Drug dissolution can be measured Techniques (BP/USP) used for dissolution testing: - Beaker method - Flask stirrer method - Rotating basket method (Figure A) - Paddle method (Figure B) - Flow-through-cell for low solubility drugs (Figure C) MPharm Preformulation- Dissolution  Product Figure A Figure B Glass or ceramic filter plate Porous filter material Tablet Peristaltic pump Filter plate Figure C MPharm Preformulation- Dissolution  Product Figure A Figure B MPharm Preformulation- Dissolution  How? Drug dissolution can be measured * dissolution testing and sink conditions: Sink conditions: CB