Formation of fine drug particles by cogrinding with cyclodextrins. I. The use of beta-cyclodextrin anhydrate and hydrate.

Abstract

To improve the micromeritical properties of pranlukast (PRK) hydrate, a cogrinding process with cyclodextrin was used, and the formation of fine drug particles was investigated. PRK crystals were ground with either beta-cyclodextrin (beta-CD) anhydrate or beta-CD hydrate crystals at a mixing molar ratio of 2:1 (beta-CD:PRK) to prepare the ground mixtures (GMs). Powder X-ray diffraction measurement and particle size analysis were performed. The two GMs differed from one another in appearance, wettability, and fine particle production. Quantitative determination demonstrated that when the beta-CD hydrate/PRK GM was dispersed in water, 96% of PRK loaded in GM became fine particles smaller than 0.8 microm. In contrast, only 1.4% of PRK in GM transformed to fine particles in the case of beta-CD anhydrate/PRK GM. The PRK fine particles were considered to be dispersed as small crystals. The stability of PRK particles in the aqueous solution was improved by the addition of a water-soluble polymer. Cogrinding with a beta-CD of higher water content can be an effective method to prepare fine drug particles at the submicron level.