Physical Pharmacy Lecture 9

Definitions and Importance

• A drug product is a finished dosage form that contains a drug substance mostly associated with other inactive ingredients.
• Drug release is the process by which the drug leaves a drug product.
• Dissolution is the process by which drug molecules are liberated from a solid phase and enter a solution phase.

Dissolution vs. Solubility

• Dissolution testing, also known as in-vitro drug release testing, measures the release of the active pharmaceutical ingredient (API) from the drug product matrix in a controlled laboratory environment.
• Dissolution is a time-dependent (or kinetic) process that involves mass transfer (like diffusion).

Factors Affecting Dissolution

• Concentration gradient: An increase in concentration gradient increases the rate of dissolution, and can be increased by decreasing the thickness of the diffusion layer or using large volumes of dissolution medium.
• Thickness of the diffusion layer (h): Decreased agitation increases the thickness of the diffusion layer, which decreases the rate of dissolution.
• Surface area of drug particles (S): Increased surface area of drug particles increases the rate of dissolution.

Methodology

• Performance testing involves subjecting the dosage form to a set of conditions that will induce drug release from the dosage form and quantifying the amount of drug released under those conditions.
• Conditions include the selection of dissolution apparatus (type and speed) and dissolution medium (sink conditions and temperature).

Official Dissolution Apparatus

• Apparatus I: Rotating Basket (50 rpm)
• Apparatus II: Paddle
• Apparatus III: Reciprocating cylinder (“Bio-Dis")
• Apparatus IV: Flow-through cell
• Apparatus V: Paddle over disk
• Apparatus VI: Rotating Cylinder
• Apparatus VII: Reciprocating Holder
• European Pharmacopeia: Chewing gum apparatus

Choice of Apparatus

• Dosage Forms:
  • Oral suspensions: USP Apparatus 2
  • Orally disintegrating tablets: USP Apparatus 2
  • Chewable tablets: USP Apparatus 2 or 3
  • Transdermal patches: USP Apparatus 5
  • Semisolid topical dosage forms: Franz-cell, enhancer cell

Special Considerations

• Dissolution conditions should be discriminatory, capable of reflecting a change in drug release profile related to a change in the drug product.
• Dissolution conditions are generally selected to simulate in-vivo conditions, not mimic them.
• Biorelevant media simulate gut fluids accurately, containing components that replicate conditions found in the GIT.

Biorelevant Medium

• Biorelevant media contain components like bile salts, phospholipids, and salts that simulate gut fluids accurately.

Noyes-Whitney Equation

• The Noyes-Whitney equation describes the dissolution rate of a drug molecule.