Exam 1 - Dissolution

Question 1

Why does dissolution matter?

Answer 1

Limited solubility in aqueous GI fluids can result in Dissolution rate-limited absorption

Question 2

Introduction of Dissolution Requirements:

Answer 2

Four different test apparatuses described in USP:

• Apparatus 1 – Basket
• Apparatus 2 - Paddle
• Apparatus 3 - Reciprocating Cylinder
• Apparatus 4 – Flow-Through Cell

Question 3

Process of Dissolution:

Answer 3

1. Interfacial reaction – liberation of solute molecules from solid to liquid phase
2. Migration of solute molecules from boundary layers surrounding the solid into the bulk solution

Question 4

Concept of Sink Conditions for Dissolution:

Answer 4

If C ≤ Cs then SINK CONDITIONS exist for dissolution

Question 5

Factors Influencing Dissolution:

Answer 5

• Surface area of undissolved solid
• Solubility of compound in dissolution medium
• Bulk solution concentration
• Diffusion Coefficient (D) & dissolution rate constant (k)

Question 6

Why perform dissolution testing?

Answer 6

1. compliance with product specifications?
2. define formula and process variables
   affecting bioavailability
3. indication of in vivo product performance

Question 7

Dissolution specifications:

Answer 7

established as part of the approval process

Question 8

Dissolution testing:

Answer 8

• Manufactured batches / lots routinely tested prior to
release for sale
• Routinely tested on stability

Question 9

Correlation of in vitro dissolution with in vivo oral bioavailability to enable:

Answer 9

Predictive Dissolution Testing

Question 10

IVIVC – In Vitro / In Vivo Correlation:

Answer 10

1. Can guide early dosage form development to

2. Surrogate for clinical studies

Question 11

Key Dissolution Testing Variables:

Answer 11

• Type of apparatus
• Volume and composition of the dissolution medium
• Hydrodynamics
• Number of units to be tested

Question 12

Dissolution Methods for Quality Control:

Answer 12

• Must be simple, reliable, reproducible, but able to detect small product deviations
• Conditions selected where at least 80% of the drug will dissolve

Question 13

Dissolution Medium:

Answer 13

• volume & composition necessary for 80% dissolution
• “Sink Conditions”
• Medium must:
     -not affect drug stability
     -simplest possible composition
     -inexpensive
     -non-organic (if possible)
     -surfactant if necessary (e.g., SLS)

Question 14

Predictive Dissolution Testing:

Answer 14

• Much more complex
• Requires conditions that mimic the chemistry /
physiology of the entire GI tract
• control of residence times surfactants, ph, mimic physiological conditions during transit
• generally requires USP 3 & 4, or non-non-compendial apparatuses
• concordant and well-controlled in vivo PK studies required for reasonable IVIVC

Question 15

Biorelevant Dissolution Media:

Answer 15

• Nutritional Liquid Products:
- Fat & protein enhance dissolution of poorly soluble
drugs
- higher pH than gastric fluid
• Simulated gastric & simulated intestinal fluid:
-with or without enzymes or bile salts (tauric acid,
lecithin)
• Bicarbonate buffers