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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Cogrinding with a beta-CD of higher water content can be an effective method to prepare fine drug particles at the submicron level.
Wongmekiat
Arpansiree
A
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
Tozuka
Yuichi
Y
Oguchi
Toshio
T
Yamamoto
Keiji
K
D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000138:chemical synthesis / Q000737:chemistry*; D008863:Microspheres; D010316:Particle Size; D013678:Technology, Pharmaceutical / Q000379:methods*; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D047392:beta-Cyclodextrins; C031215:betadex