Optimization of the formulation of solid multiparticulate dosage forms containing pancreatin

The objective of this study was to investigate the changes in the starch-hydrolysing activity of pancreatin under conditions that can occur during the formulation of multiparticulate systems (granulation, direct compression for the preparation of minitablets and coating). Direct compression did not induce a significant alteration in the starch-hydrolysing activity. A factorial design was applied in the testing of the wet conditions ensured by water and ethanol. These had a significant impact, though ethanol caused a more relevant decrease. An increased content of liquid was necessary for unwanted effects, but the changes of its amount in the tested range were not highly relevant. In both cases, the most important factor in the investigation of wet conditions was temperature. During the study of the effects of modelling of the circumstances of tabletting, elevated temperature did not cause alterations in the relatively dry material. This information can promote an improved design for the preparation of the dosage form. Pelletization is not appropriate for the preparation of an intermediate. Direct compression is the most suitable formulation step. Coating must be performed at low temperature with aqueous systems, but rapid drying is also advisable for the first separating layer. A mathematically based optimization can be necessary for the preformulation study of the preparation of dosage forms containing sensitive enzymes.