Dissolution Testing in Pharmaceutical Analysis (Part 1)

The dissolution test is a key test parameter routinely used for assessing the performance of solid and semi-solid dosage forms in both drug development and quality control.

Purpose

The dissolution is used to assure batch-to-batch quality as well as providing process control information as part of the approach to process validation. The test is used to measure the release of an API from its formulation under standardized conditions.

The European Pharmacopoeia (Ph. Eur.) describes dissolution tests in the general part in section 2.9. Pharmaceutical technical procedures.

Chapter 2.9.3 Dissolution Test for Solid Dosage Forms

Chapter 2.9.3 of the European Pharmacopoeia describes different methods and apparatuses to determine compliance with the dissolution requirements for solid dosage forms administered orally.

The following apparatuses are described:

• Apparatus 1 (Basket apparatus)
• Apparatus 2 (Paddle apparatus)
• Apparatus 3 (Reciprocating cylinder)
• Apparatus 4 (Flow-through cell)

The dimensions and tolerances of the listed apparatus are specified precisely in each case. The determination of the suitability of the apparatus to perform dissolution testing must include conformance to these parameters. Critical test parameters that have to be monitored periodically during use include volume and temperature of the dissolution medium, rotation speed (Apparatus 1 and 2), dip rate (Apparatus 3), and flow rate of medium (Apparatus 4).

In the subchapters "Procedure" and "Interpretation", the use of the apparatuses for

• Conventional-release solid dosage forms,
• Prolonged-release dosage forms,
• Delayed-release dosage forms

is described.

Chapter 2.9.4 Dissolution Test for Transdermal Patches

Chapter 2.9.4 describes a test to determine the dissolution rate of the active ingredients of transdermal patches. Usually, the paddle and vessel assembly from the paddle apparatus described in the dissolution test for solid oral dosage forms (2.9.3) is used. The monograph describes three test apparatuses for this purpose:

• Disk assembly method
• Cell method
• Rotating cylinders

Chapter 2.9.25 Dissolution Test for Medicated Chewing Gums

This chapter describes how to determine the dissolution rate of active substances in medicated chewing gums.

Medicated chewing gums have been defined as solid, single-dose preparations with a base consisting mainly of gum that are intended to be chewed but not swallowed. They contain one or more active substances which are released by chewing. Thus, the primary process for the release of the active ingredient is the chewing of the mass. According to Chapter 2.9.25 this process is simulated by applying a mechanical kneading procedure to a piece of gum placed in a small chamber.

Two apparatuses are described for this purpose. Apparatus A, consists of a metal chamber, two horizontal oscillatory testing device pistons, which simulate the mastication, and a third, vertical piston to keep the chewing gum in place during the test.

To perform the measurement, a dissolution medium, usually phosphate buffer solution, is placed in the chewing chamber. The medium temperature is maintained at 37 ± 0.5 °C. At the prescribed time, the apparatus is stopped, the gum residue is removed, and a sample of the dissolution medium is taken. The content of active substance(s) is then determined by a suitable method. In Apparatus B, the chewing is simulated by one vertical oscillatory piston and one stationary rotating piston.

Chapter 5.17.1 Recommendations on Dissolution Testing

This general chapter, which is non-mandatory, contains further information on the following aspects:

• Experimental testing conditions
• Recommended dissolution media
• Qualification and validation
• Expression of dissolution specifications for oral dosage forms