II. Segregation of Active Constituents from Tablet Formulations During Grinding: Significance to Pharmaceutical Analysis

Abstract

The preparatory step in the analysis of active drugs in tablet dosage forms has generally consisted of the grinding or milling of a given number of the tablets into a fine powder. Certain drugs formulated as tablets have been shown to undergo physical separation from other tablet components as a result of grinding. This phenomenon accounts, at least in part, for the poor reproducibility found in duplicate assays for these drugs in tablet composites. This same phenomenon also explains discrepancies between the average of the individual tablet assay values of samples prepared by direct dissolution, and the assay value of the corresponding composites.

This paper illustrates this phenomenon using a problem dosage form and suggests methods of sample preparation that avoid segregation of ingredients. These methods include the direct dissolution of a representative number of individual tablets in a suitable solvent, the sieving and regrinding of the ground tablets, the grinding of a composite with a suitable organic solvent and the evaporation of the solvent, and the dissolution of the total composite tablet sample in a solvent.