Effects of solid-state reaction between paracetamol and cloperastine hydrochloride on the pharmaceutical properties of their preparations.
Tablets containing both paracetamol (PM) and cloperastine hydrochloride (CLH) in a combination formulation prepared by standard vertical granulation technology were found to have altered pharmaceutical properties. The hardness and disintegration time of tablets containing both PM and CLH gradually increased during storage, and the cross-screw did not operate smoothly during preparation of the mixed powder. The objective of the present study was to investigate the mechanism of formation of eutectic mixtures consisting of PM and CLH. Binary mixtures of PM and CLH in various proportions were prepared as physical mixtures and analyzed by DSC to study their thermal behavior. Phase diagrams obtained from the endothermic peaks due to melting of physical mixtures of PM and CLH demonstrated the formation of eutectic mixtures with eutectic temperatures of 86.9-110.2 degrees C depending on the ratio of constituents. The formation of the eutectic mixture was studied for a 50:50 mol.% ratio of PM and CLH. PXRD analysis revealed that the eutectic mixture of PM and CLH is structurally different from native PM and CLH. The most probable interaction sites between PM and CLH were demonstrated by DSC analysis of a binary mixture of PM and CLH prepared by melt quenching.
Sakata
Yukoh
Y
Healthcare Research Institute, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Kodacho, Akitakatashi, Hiroshima 739-1195, Japan. Electronic address: sakata_y@wakunaga.co.jp.
Tanabe
Eishi
E
Western Hiroshima Prefecture Industrial Research Institute, 3-13-26 Kagamiyama, Higashi-Hiroshima 739-0046, Japan.
Sumikawa
Toshiharu
T
Healthcare Research Institute, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Kodacho, Akitakatashi, Hiroshima 739-1195, Japan.
Shiraishi
Sumihiro
S
Healthcare Research Institute, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Kodacho, Akitakatashi, Hiroshima 739-1195, Japan.
Tokudome
Yoshihiro
Y
Department of Pharmaceutical Technology, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, Shinmachi 1-1-20, Nishi-Tokyo 202-8585, Japan.
Otsuka
Makoto
M
Department of Pharmaceutical Technology, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, Shinmachi 1-1-20, Nishi-Tokyo 202-8585, Japan.
D000082:Acetaminophen / Q000737:chemistry*; D018712:Analgesics, Non-Narcotic / Q000737:chemistry*; D000996:Antitussive Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D004338:Drug Combinations; D004355:Drug Stability; D006244:Hardness; D006860:Hydrogen Bonding; D008855:Microscopy, Electron, Scanning; D044367:Phase Transition; D010880:Piperidines / Q000737:chemistry*; D011208:Powders; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets; D013678:Technology, Pharmaceutical; D013696:Temperature; D013997:Time Factors
D018712:Analgesics, Non-Narcotic; D000996:Antitussive Agents; D004338:Drug Combinations; D010880:Piperidines; D011208:Powders; D013607:Tablets; D000082:Acetaminophen; C040282:cloperastine