Release mechanism of drugs, packed in hard gelatin capsules.

摘要

It is the aim of this study to gain a better insight in the release mechanism of drugs, packed in hard gelatin capsules.;An investigation of 77 different industrially prepared capsules shows that the disintegration of the powderbed seems to be the rate limiting step in the process of the drug release.;Several methods were developed to investigate the factors that can influence this drug release from capsules, and especially the disintegration of the powder plug and the dissolution rate of a model drug (phenacetin). Among these are a fully automated dissolution rate testing system and a capsule filling apparatus that allows to monitor and control the capsule filling conditions.;The most important factors that were investigated are: (1) Wettability of the powder; (2) porosity of the powder bed; (3) liquid penetration rate; (4) swelling properties of the excipients; (5) solubility of the excipients.;Both porosity and wettability appear to have an influence on liquid penetration, but their impact is not identical.;An improved liquid penetration results in but minor improvements in disintegration time and drug release. Indeed, a fast penetration of the liquid in the powder plug does not guarantee a rapid disintegration.;From the study on the effect of swelling substances it can be concluded that the increase in volume and diameter of the particles has an important influence on drug release from gelatin capsules, but it is also clear that it is not the only parameter that determines the efficiency of a swelling disintegrant.