| Popis: |
The release rate of an active ingredient from a dosage form may be affected by the agglomeration of an active ingredient before tablet compression. This study is aimed at establishing the effects of the agglomerates on active ingredient release profiles. A model substance, caffeine, was tested in the powdered form and in the two agglomerated forms prepared by wet granulation and compaction. The profiles of caffeine release from these forms were measured using a flow-through cell dissolution apparatus (USP 4) in an open-loop arrangement. To identify the particular processes responsible for the differences in the dissolution profiles of the model forms, we developed a mathematical description of the dissolution profiles. Using this mathematical approach, we proposed that caffeine was adsorbed to the microcrystalline cellulose present in the granulated and compacted form and that diffusion of the active ingredient was inhibited in the presence of a binder in the granulate. Both of these effects resulted in imperfections in the shape of dissolution profiles and in a decrease in the dissolution rate of caffeine. The mathematical model is based on generic parameters, thus it is transferable to other pharmaceutical substances in powdered and agglomerated forms. |
