Laser Diffraction Estimation of Particle Size Distribution of Slightly Water-Soluble Drugs Coexisting with Additives : Application to Solid Dosage Forms

Abstract

A simple and quantitative evaluation method for particle size distribution (f_x(r)) of slightly water-soluble drugs dispersed in an aqueous medium together with other water-insoluble additives was developed using a laser diffraction method.The particle size distribution function of the powder mixture, (f(r)), was assumed as f(r)=φ_x·f_x(r)+φ_a·f_a(r), where φis the volume fraction of each component dispersed in a measurement medium and f_a(r) is the distribution function of another water-insoluble additive "a".In order to calculate f_x(r) from f(r), it is necessary to know the density of drug and additive in the measurement medium, d_x and d_a, but this is difficult to determine since particles usually swell in the medium. Thus, a method was developed to use their relative value δ_a (=d_a/d_x).As a practical application, oxolinic acids (OA) of three sizes (OA-S (about 2μm), OA-M (about 7μm) and OA-L (about 24μm)) were used as model drugs. δ_a values were determined for various additives using the mixture of OA-S and each additive. Then, using δ_as, f_x(r) of OA-M or OA-L in the mixture containing OA-M or OA-L and additives was calculated from the f(r)experimentally determined for the mixture. They agreed well with their original distributions.The method was applied to some dosage forms, and the results obtained had good correlation with those from turbidity, wet sieving or dissolution test.