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

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 (mp) 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 mp values of the theoretically estimated release curves were generally higher, while their t∞ values were generally shorter than the corresponding values for the experimental curves. Conclusion: The indication is that drug release from the multi-unit dose tablets was more retarded than could be theoretically estimated. Apparently, the two components interfere with each other’s release