EFFECT OF PARTICLE-SIZE ON DEFORMATION AND COMPACTION CHARACTERISTICSOF ASCORBIC-ACID AND POTASSIUM-CHLORIDE - NEAT AND GRANULATED DRUG

Deformation and compaction characteristics of two soluble drugs, ascor bic acid and potassium chloride, were investigated. Five different par ticle size fractions of ascorbic acid with mean particle size (d(50)) ranging from 30-300 mu m and four different particle size fractions of potassium chloride with d(50) ranging from 20-400 mu m were selected in the study. The compaction behavior of the drug substances as neat d rugs or as granulated drugs were evaluated on both a Carver press and an instrumented single-punch tablet press. The results clearly show th at mean particle size of the drug substances plays an important role i n their compactibility. Intrinsic compactibility of both drug substanc es was slightly improved with increased particle size. Granulations of the drugs with polyvinyl pyrrolidone significantly improved their com pactibility. However, this effect was more pronounced in the drug subs tance with finer particle size. The Heckel plots indicate that deforma tion characteristics of both granulated drugs were related to their or iginal mean particle sizes. The granulations prepared from the coarser particle size (d(50) 250 mu m to 400 mu m) underwent two stages of de formation, so-called ''brittle fracture'' and ''plastic deformation''. While the granulations prepared from the finer particle size predonin antly underwent ''plastic deformation''. The results indicated that th e plastic deformation of both granulated drugs was progressively enhan ced whilst fragmentation of particles was correspondingly reduced as t he particle size of the drugs was decreased. Scanning electron photomi crographs indicated that the granulation process changed the surface m orphology 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 asco rbic acid and potassium chloride for satisfactory compactibility was f ound to be 30-40 mu m and 20-40 mu m, respectively. The present study demonstrates the importance of selecting the appropriate particle size of drug for the development of tablet dosage forms.