The influence of pH of dissolution fluid and particle size of drug on the in-vitro release of drug from hard gelatin capsules.

The influence of pH of the dissolution fluid on the in-vitro release of acetylsalicylic acid from hard gelatin capsules has been studied for a series of particle size fractions of the drug. Generally, the time required for 50% of the drug content of the capsule to appear in solution during a dissolution test, T50, increased as the pH increased from 1.2 to 2.0; thereafter the value of T50 decreased as the pH increased from 3 to 7. These changes were found to be related to the apparent solubility of the drug. The extent of the changes was found to be further dependent on the particle size of the drug. For capsules filled with particle size fractions of 2.5 and 5.5 microns median diameter, the changes were small. Larger changes were observed with particles of median diameters of 45, 100, 220 and 330 microns while the largest changes (greater than two-fold) were obtained with particles of median diameter 130 and 430 microns. The type of kinetics that could be used to express the release rates was found to be particle size-dependent. For particles of 45 microns and larger, the release rate followed an apparent zero order process while an apparent first order process represented the release for the two smallest particle size fractions.