Effect of Particle Size on Deformation and Compaction Characteristics of Ascorbic acid and Potassium Chloride: Neat and Granulated Drug

Abstract

Deformation and compaction characteristics of two soluble drugs, ascorbic acid and potassium chloride, were investigated. Five different particle size fractions of ascorbic acid with mean particle size (d50) ranging from 30–300μm and four different particle size fractions of potassium chloride with d50 ranging from 20–400 μm were selected in the study. The compaction behavior of the drug substances as neat drugs or as granulated drugs were evaluated on both a Carver press and an instrumented single-punch tablet press. The results clearly show that mean particle size of the drug substances plays an important role in their compactibility. Intrinsic compactibility of both drug substances was slightly improved with increased particle size. Granulations of the drugs with polyvinyl pyrrolidone significantly improved their compactibility. However, this effect was more pronounced in the drug substance with finer particle size. The Heckel plots indicate that deformation characteristics of both granulated drugs were related to their original mean particle sizes. The granulations prepared from the coarser particle size (d50 250 μm to 400 μm) underwent two stages of deformation, so-called “brittle fracture” and “plastic deformation”. While the granulations prepared from the finer particle size predoninantly underwent “plastic deformation”. The results indicated that the plastic deformation of both granulated drugs was progressively enhanced whilst fragmentation of particles was correspondingly reduced as the particle size of the drugs was decreased. Scanning electron photomicrographs indicated that the granulation process changed the surface morphology of the drug particles imparting more “microirregularities” or “defects”, thereby providing greater “interparticulate bonding” as compared with the neat drugs. Optimum particle size range of ascorbic acid and potassium chloride for satisfactory compactibility was found to be 30–40 μm and 20–40 μm, respectively. The present study demonstrates the importance of selecting the appropriate particle size of drug for the development of tablet dosage forms.