Preformulation studies of a novel camptothecin anticancer agent, CKD-602: physicochemical characterization and hydrolytic equilibrium kinetics.
(20S)-7-(2-isopropylamino)ethylcamptothecin.HCl (CKD-602), a new camptothecin (CPT) anticancer agent, is a pale yellowish crystalline compound. DSC thermogram exhibited a melt endotherm near 270 degrees C, and CKD-602 was found to be slightly hygroscopic. The solubility of CKD-602 in deionized water was 8.22 mg/ml, and two pK(a) values were measured to be 2.32 and 9.15, respectively. A pH-dependent partition coefficient behavior in octanol-buffer was observed. CKD-602 in solid state was stable over the range of temperature and humidity, but decomposed slightly by light. The hydrolysis of CKD-602 occurred reversibly and rapidly in aqueous buffer solutions. The conversion rate constants (k(f): from the lactone to the carboxylate and k(r): from the carboxylate to the lactone) and the final equilibrium ratio (K(eq)) between two species were dependent on the pH of aqueous solutions.
Kim
Jae-Hyun
JH
DDS Research Lab, Pharmaceutical Research Labs, CKD Research Institute, Chong Kun Dang Pharm., Chonan PO Box 74, Chonan 330-600, South Korea. jhjaykim@dreamwiz.com
Lee
Seok-Kyu
SK
Lim
Jong-Lae
JL
Shin
Hee-Jong
HJ
Hong
Chung Il
CI
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006813:Humidity; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D012995:Solubility; D012997:Solvents; D013696:Temperature
D000972:Antineoplastic Agents, Phytogenic; D012997:Solvents; C116963:belotecan; D002166:Camptothecin