Dissolution

Question 1

Dissolution Def

Answer 1

Rate at which drug dissolves. Liberating itself from dosage form. 2 Stages interfacial reaction and migration

Question 2

Intrinsic Dissolution rate Def

Answer 2

Transfer rate of ions/molecules from solid to molecular dispersion per unit time through a known surface area

Question 3

Steps of Interfacial Reaction

Answer 3

Solute molecule removed from crystal, creation of cavity in solvent and insert solute molecule into cavity

Question 4

Relationship between solubility, dissolution and diffusion

Answer 4

Higher solubility = higher diffusion = higher dissolution

Question 5

Migration Outline

Answer 5

Dissolved molecules moving from interface to bulk solution via diffusion. Needs to move through static layer of undissolved drug at interface (slower). Rate limiting step for absorption extent

Question 6

Dissolution Equation

Answer 6

Noyes-Whitney equation

Question 7

Dissolution (rate of solution) notation

Answer 7

dm/dt

Question 8

Conc diff across a boundary layer notation

Answer 8

Cs - C

Question 9

Diffusion Coefficent Notation

Answer 9

K1 or D

Question 10

Thickness of boundary layer notation

Answer 10

h

Question 11

Relationship between dissolution and diffusion coefficent

Answer 11

Higher dissolution = higher diffusion coefficent

Question 12

Relationship between surface area and diissolution

Answer 12

Higher surface area = higher dissolution

Question 13

Relationship between conc across boundary and dissolution

Answer 13

Higher conc across gradient = higher dissolution

Question 14

Relationship between boundary layer thickness and dissolution

Answer 14

Higher thickness = lower dissolution

Question 15

Surface Area Factors

Answer 15

particle size, solid disintegration and air pockets in particles

Question 16

Saturation Solubility (Cs) def.

Answer 16

Temp, medium nature, solute molecular structure, solid crystalline form and presence/absence of compound

Question 17

Solute Conc in solution at a time (C) Factors

Answer 17

medium volume and drug removal (eg absorption)

Question 18

Diffusion Coefficent Factors

Answer 18

Temp, molecule diameter and viscosity

Question 19

Boundary Layer Thickness Factors

Answer 19

Agitation Degree

Question 20

How is dissolution used in manufacturing

Answer 20

Quality control test (efficacy and safety). Tests excipients (eg too much binder). Rapid dissolution = >85% dissolved within 30 mins, in 900ml of solvent at 37 degrees. Regulatory approval and predictio nof dosage form behaviour

Question 21

Sink Condition (0 order release)

Answer 21

Solution removed from dissolution environment 10% slower then solute. Solution builds up. <10% saturation solubility should be in bulk solution

Question 22

Noyes Whitney Limits

Answer 22

Equation assumes that particle size remains constant throughout dissolution. This doesn’t reflect reality where particle size decreases over dissolution except for under sink conditions

Question 23

Physiology Factors influence in vivo conditions

Answer 23

GI fluid vol, co-administerd fluid vol, fasted/fed, residence time, disease state, surfactant conc and diet (mixing of different)

Question 24

Fluid Volume in Body Outline

Answer 24

Different in different regions of body. Low in oral cavity and high in small intestine

Question 25

Physiochemical properties in vivo dissolution of oral dosage

Answer 25

Solubility (Log P, Melting Point, Physical Form, pKa), molecular weight, particle size, physical behaviour and wettability

Question 26

Formulation Factors in Dosage form

Answer 26

Dosage form, particle size, release properties (admin form eg Immediate RElease (IR) or controlled release (CR)) and excipient composition