Effect of characteristics of compounds on maintenance of an amorphous state in solid dispersion with crospovidone.
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.
Shibata
Yusuke
Y
Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, Japan.
Fujii
Makiko
M
Kokudai
Makiko
M
Noda
Shinobu
S
Okada
Hideko
H
Kondoh
Masuo
M
Watanabe
Yoshiteru
Y
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
D004337:Drug Carriers; D006118:Griseofulvin; D014192:Trapidil; D011205:Povidone