Effect of a Change in Crystal Polymorph on the Degree of Adhesion Between Micronized Drug Particles and Large Homogenous Carrier Particles During an Interactive Mixing Process

Abstract

This study reports the effect of a change in crystal form on the quality of interactive mixtures prepared with homogenous sugar beads and the three polymorphs of chloramphenicol palmitate (CAP). Six mixtures containing micronized CAP polymorph powder (0.5%) and sugar beads (99.5%) were mixed in a Turbula® mixer at 27 rpm or 54 rpm for 2.5, 5, 10, or 20 min. Three of the six mixtures was screened to remove the unmixed drug powder. The content uniformity (CV %) of the three screened and three unscreened mixtures was determined by determining the variation in drug content of 10 randomly taken samples from each mixture. Comparison of the amount of drug screened and the content uniformity of the mixtures showed that at short mixing times and 27 rpm and longer mixing times of 10 and 20 min at 54 rpm, the three crystal forms formed interactive mixtures with statistically the same content uniformity. In contrast at 54 rpm and mixing for 5 min and shorter, form A formed less homogeneous interactive mixtures compared with forms B and C. Consistently at both mixing speeds a larger amount of form A, compared with forms B and C, was screened from the mixtures. The results showed that the affinity between forms B and C and the carrier sugar beads is higher than that between form A and the sugar beads. Therefore, changing the crystal form of a drug influences the affinity between the drug and a carrier when preparing interactive mixtures.