Effect of Cyclodextrins on the Hydrolysis of an Oxazolidine Prodrug of (1R,2S)-(−)-Ephedrine–cis-2-(4-Methoxyphenyl)-3,4-dimethyl-5-phenyloxazolidine

✍ Scribed by R. Bakhtiar; C. E. C. A. Hop; R. B. Walker

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 220 KB
• Volume: 11
• Category: Article
• ISSN: 0951-4198
• DOI: 10.1002/(sici)1097-0231(199704)11:6<598::aid-rcm903>3.0.co;2-v

✦ Synopsis

Molecular complexes of an oxazolidine prodrug of (-)-ephedrine, cis-2-(4-methoxyphenyl)-3,4-dimethyl-

5-phenyloxazolidine, with α-, β-, dimethyl-β-(DM-β-) and hydroxypropl-β-(HP-β-) cyclodextrins (CDs) were examined using ionspray mass spectrometry. The results suggest, under our experimental conditions, a 1:1 stoichiometric complex between the prodrug and all CDs. Apart from the putative inclusion complexation, the stabilization effect of CDs on the prodrug in an aqueous solution was studied. β-, DM-β-and HP-β-CD exhibited a retardation effect on the rate of hydrolysis of the prodrug. Conversely, α-CD did not alter the rate of hydrolysis even at excess concentrations. Presumably, the larger cavity diameter of β-CDs may permit a greater depth of penetration of the prodrug, resulting in its shielding from hydrolysis. The observations in this work indicate that mass spectrometry could be a rapid and informative analytical method to aid in the preliminary evaluation of the potential utility of CDs in enhancement of drug stability.