Effect of drug particle size on content uniformity of low-dose solid dosage forms

Abstract

Two low-dose blends were prepared that differed only in the particle size of the drug used to make the blends. The geometric mean particle diameters for the two lots of drug used were 18.5 and 6.1μm. Samples of the blends approximately equivalent to the unit dose of 10 μg per 99 mg of blend were assayed for potency. For the blend containing the larger particle size drug, the potency range was 88–130% ( n = 65) compared to 97–102% ( n = 64) for the blend containing the smaller particle size drug. A simple computer method was able to qualitatively simulate the observed potency profiles using only the particle size distribution of the drug and assuming ideal mixing. The method provides guidance in setting particle size specifications to avoid poor content uniformity.