The Dissolution Test

In order for a dissolution test to demonstrate the unique dissolution characteristics of the dosage form, the dissolution procedure should be based on the physical and chemical properties of the drug substance as well as the dosage form characteristics. Some of the physical-chemical properties of the drug substance which influence the dissolution characteristics are:

• solubility in water and other solvents

• effect of pH on solubility-ionization constants

• solution stability

• particle size/surface area

• common ion effects

• ionic strength

• buffer effects

• octanol/water partition coefficients

• effect of temperature on solubility

Once the drug substance properties have been determined, the actual dosage form needs to be considered. For example, is the dosage form a tablet, capsule, semi-solid (ointment or cream), or transdermal and is the dosage form designed for immediate release or controlled release of the drug product? Of key importance is the potency of the dosage form or the amount of drug to be delivered and the rate at which the drug is to be delivered. This relates directly to the mathematical expression of dissolution rate which is defined by the Noyes-Whitney equation:

ki = a dissolution constant

Csat = the concentration of a saturated solution

Cgol = the concentration of the solution at any given time

S = the surface area of the solid

In vivo, the gastrointestinal tract acts as a natural sink, i.e., the drug is absorbed as it dissolves. In vitro, sink conditions are simulated by using either a large volume of dissolution medium or by replenishing the medium with fresh solvent at a specific rate. (By keeping the volume of dissolution medium at least five to ten times greater than the saturation volume, sink conditions are approximated [6])1. When sink conditions are achieved, Csat > > CSol, the equation simplifies to:

where:

—= the dissolution rate dt

where:

1 According to the USP <1088>, the quantity of medium used should be not less than three times that required to form a saturated solution.

-= the dissolution rate dt k2 = a dissolution constant

S = the surface area of the solid

In this case, the dissolution rate is characteristic of the release of active ingredient from the dosage form rather than the solubility in the dissolution medium. Therefore, sink conditions are one of the main experimental parameters to be controlled in dissolution testing. Sink conditions can be achieved by the appropriate selection of the dissolution apparatus and dissolution medium. Based on drug substance and dosage form characteristics, the appropriate dissolution apparatus should be selected.

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