Effects of sugar ester and hydroxypropyl methylcellulose on the physicochemical stability of amorphous cefditoren pivoxil in aqueous suspension.
The improvement in physicochemical stability of amorphous cefditoren pivoxil (CDTR-PI) in aqueous suspensions by addition of sugar ester (SE) and hydroxypropyl methylcellulose (HPMC) was explained by prolonging the induction period prior to crystallization and the reduction in crystal peak intensity. Furthermore, the stabilizing effect of these additives in a multiple additive system was greater than in a single additive system. To determine the mechanism, by which these additives stabilized the amorphous CDTR-PI, we evaluated the surface states of CDTR-PI in suspension by measuring Raman spectra and zeta potential. The change in Raman spectra demonstrated that SE and HPMC interacted with CDTR-PI at the same interaction sites on CDTR-PI. The zeta potential reflected the adsorption phenomena of the additives and indicated that both SE and HPMC adsorbed onto particles of CDTR-PI with no apparent competitive interaction and the response was complementary. It was considered, based on this study, that HPMC and SE would stabilize amorphous CDTR-PI by different mechanisms; HPMC would mainly inhibit crystal growth by small amount of adsorption and SE would inhibit both crystal growth and nucleation by large amount of adsorption. This was considered to result in the hybrid effect in the multiple additive system.
Yokoi
Yukiko
Y
Chemistry, Manufacturing and Control Research Laboratories, Pharmaceutical Development Department, Meiji Seika Kaisha Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan. yukiko_ishikawa@meiji.co.jp
Yonemochi
Etsuo
E
Terada
Katsuhide
K
D002241:Carbohydrates / Q000032:analysis / Q000737:chemistry*; D002511:Cephalosporins / Q000032:analysis / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004355:Drug Stability; D004952:Esters; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry*; D019999:Pharmaceutical Solutions / Q000032:analysis / Q000737:chemistry; D014867:Water / Q000032:analysis / Q000737:chemistry
D002241:Carbohydrates; D002511:Cephalosporins; D004952:Esters; D019999:Pharmaceutical Solutions; D014867:Water; D065347:Hypromellose Derivatives; C057710:cefditoren pivoxil; D008747:Methylcellulose