title: Effect of characteristics of compounds on maintenance of an amorphous state in solid dispersion with crospovidone.
abstract: Solid dispersion (SD) of indomethacin with crospovidone (CrosPVP) shows useful characteristics for preparation of dosage forms. This study aimed to determine the types of drugs that could adopt a stable amorphous form in SD. Twenty compounds with various melting points (70-218 degrees C), molecular weights (135-504) and functional groups (amide, amino, carbonyl, hydroxyl, ketone etc.) were prepared in SD with CrosPVP. The CrosPVP SDs were prepared using a mechanical mixing and heating method. Melting point and molecular weight were found to have no influence on the ability of a compound to maintain an amorphous state in SD. All compounds containing hydrogen-bond-donor functional groups existed in an amorphous state in SD for at least 6 months. Infrared spectra suggested an interaction between the functional groups of these compounds and amide carbonyl group of CrosPVP. Compounds without hydrogen-bond-donor groups could not maintain an amorphous state and underwent recrystallization within 1 month. It was suggested that the presence of a hydrogen-bond-donor functional group in a compound is an important factor affecting the stable formation of SD with CrosPVP, which contains a hydrogen-bond acceptor.
authors.affiliation: Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shibata
authors.forename: Makiko
authors.initials: M
authors.lastname: Fujii
authors.forename: Makiko
authors.initials: M
authors.lastname: Kokudai
authors.forename: Shinobu
authors.initials: S
authors.lastname: Noda
authors.forename: Hideko
authors.initials: H
authors.lastname: Okada
authors.forename: Masuo
authors.initials: M
authors.lastname: Kondoh
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D004337:Drug Carriers; D006118:Griseofulvin / Q000008:administration & dosage / Q000737:chemistry; D006860:Hydrogen Bonding; D011205:Povidone / Q000008:administration & dosage*; D013055:Spectrophotometry, Infrared; D014192:Trapidil / Q000008:administration & dosage / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D006118:Griseofulvin; D014192:Trapidil; D011205:Povidone