Dissolution Flashcards
Dissolution Def
Rate at which drug dissolves. Liberating itself from dosage form. 2 Stages interfacial reaction and migration
Intrinsic Dissolution rate Def
Transfer rate of ions/molecules from solid to molecular dispersion per unit time through a known surface area
Steps of Interfacial Reaction
Solute molecule removed from crystal, creation of cavity in solvent and insert solute molecule into cavity
Relationship between solubility, dissolution and diffusion
Higher solubility = higher diffusion = higher dissolution
Migration Outline
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
Dissolution Equation
Noyes-Whitney equation
Dissolution (rate of solution) notation
dm/dt
Conc diff across a boundary layer notation
Cs - C
Diffusion Coefficent Notation
K1 or D
Thickness of boundary layer notation
h
Relationship between dissolution and diffusion coefficent
Higher dissolution = higher diffusion coefficent
Relationship between surface area and diissolution
Higher surface area = higher dissolution
Relationship between conc across boundary and dissolution
Higher conc across gradient = higher dissolution
Relationship between boundary layer thickness and dissolution
Higher thickness = lower dissolution
Surface Area Factors
particle size, solid disintegration and air pockets in particles
Saturation Solubility (Cs) def.
Temp, medium nature, solute molecular structure, solid crystalline form and presence/absence of compound
Solute Conc in solution at a time (C) Factors
medium volume and drug removal (eg absorption)
Diffusion Coefficent Factors
Temp, molecule diameter and viscosity
Boundary Layer Thickness Factors
Agitation Degree
How is dissolution used in manufacturing
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
Sink Condition (0 order release)
Solution removed from dissolution environment 10% slower then solute. Solution builds up. <10% saturation solubility should be in bulk solution
Noyes Whitney Limits
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
Physiology Factors influence in vivo conditions
GI fluid vol, co-administerd fluid vol, fasted/fed, residence time, disease state, surfactant conc and diet (mixing of different)
Fluid Volume in Body Outline
Different in different regions of body. Low in oral cavity and high in small intestine
Physiochemical properties in vivo dissolution of oral dosage
Solubility (Log P, Melting Point, Physical Form, pKa), molecular weight, particle size, physical behaviour and wettability
Formulation Factors in Dosage form
Dosage form, particle size, release properties (admin form eg Immediate RElease (IR) or controlled release (CR)) and excipient composition
