Effect of Particle Size of Drug on Conversion of Crystals to an Amorphous State in a Solid Dispersion with Crospovidone

• Published in: Chemical & Pharmaceutical Bulletin Vol. 59; no. 2; pp. 235 - 238
• Main Authors: Yuka SUGAMURAa, Makiko FUJIIa, b, Sayaka NAKANISHIa, Ayako SUZUKIa, Yusuke SHIBATAa, c, Naoya KOIZUMIa, Yoshiteru WATANABEa
• Format: Journal Article
• Language: Japanese
• Published: Pharmaceutical Society of Japan 2011
• ISSN: 0009-2363; 1347-5223

The effect of particle size on amorphization of drugs in a solid dispersion (SD) was investigated for two drugs, indomethacin (IM) and nifedipine (NP). The SD of drugs were prepared in a mixture with crospovidone by a variety of mechanical methods, and their properties investigated by particle sizing, thermal analysis, and powder X-ray diffraction. IM, which had an initial particle size of 1μm and tends to aggregate, was forced through a sieve to break up the particles. NP, which had a large initial particle size, was jet-milled. In both cases, reduction of the particle size of the drugs enabled transition to an amorphous state below the melting point of the drug. The reduction in particle size is considered to enable increased contact between the crospovidone and drug particles, increasing interactions between the two compounds. Improving dissolution properties of poorly water-soluble drugs is of major interest to pharmaceutical researchers because it is a key step in enhancing the bioavailability of drugs, and many new drug candidates discovered by combinatorial chemistry and high-throughput screening have had this problem. Various methods have been reported to improve the dissolution properties, one of which is formation of a solid dispersion (SD).