Estimation of the release profiles of multi-unit dose tablets of theophylline from the release profiles of their components

Mu Uhumwangho,Rs Okor

doi:10.4314/tjpr.v7i2.14682

Abstract

Purpose: The objective of this study is to investigate whether the drug release profile of a multi-unit dose form consisting of fast and slow release components can be predicted from the release profiles of their components by simple summation. Method: The fast release component consisted of conventional granules of theophylline made by wet massing the drug powder with starch mucilage (20%w/v). The slow release component consisted of matrix granules of the drug made by triturating the drug powder with melted carnuba wax (i.e. melt granulation). Each type of granules was compressed to tablets of weight 100, 150 or 200mg. To form the multi-unit dosage tablets of drug content 300mg each, the conventional and matrix granules were mixed in the ratio 1:2, 1:1 and 2:1, and compressed. The tablets were subjected to dissolution test and from the experimental release curve the prompt release (m p) in the first 1h, the maximum release (m �) and the time to attain it (t �) were obtained. Result: For a given composition of the multi-unit dose tablets, the theoretical release curve was obtained by summation of the release from each component at the different time intervals. The m p values of the theoretically estimated release curves were generally higher,

Highlights

Single dosage forms usually consist of drug particles of same release profile while a multi-unit dosage system consists of particles of different drug or same drug particles but of differing release profiles with respect to onset, rate and the maximum release, etc[1, 2]
The release rate of drug particles may be retarded by a process of melt granulation whereby the drug powder is triturated with a melted wax to form matrix granules which do not disintegrate to their primary particles upon contact with aqueous fluid[5]
The objective of the present study was to investigate whether the release profile of the multi-unit dose tablets can be predicted from the known profiles of the individual components that make up the multi-unit system

Summary

Introduction

Single (unit) dosage forms usually consist of drug particles of same release profile while a multi-unit dosage system consists of particles (units) of different drug or same drug particles but of differing release profiles with respect to onset, rate and the maximum release, etc[1, 2]. Capsules or tablets can be used either as single unit or multi-unit dosage forms for controlled release applications by formulating them with special excipients[3, 4]. Multiple–unit dosage forms offer advantages over the single-unit systems[1] by producing an initial prompt release followed by a sustained release to prolong the initial therapeutic effect, obviating the need for repeat dosage. A recent study[6] showed that tableting rather than encapsulation of the matrix particles is more effective in prolonging the release of the test drug. Multi-unit tablets of theophylline were formulated by mixing conventional and matrix granules of the drug in various proportions. The objective of the present study was to investigate whether the release profile of the multi-unit dose tablets can be predicted from the known profiles of the individual components that make up the multi-unit system. Theophylline was considered a candidate for the multi-unit dose formulation because it is indicated for the treatment of chronic asthma requiring prolonged medication

Objectives

Methods

Results

Conclusion