Solubilization and stabilization of a benzylpenicillin chemical delivery system by 2-hydroxypropyl-beta-cyclodextrin.
A dihydropyridine----pyridinium salt redox carrier-based chemical delivery system for benzylpenicillin (1) was complexed with 2-hydroxypropyl-beta-cyclodextrin (HPCD). The solubility of the lipophilic 1, which is incompatible with aqueous formulations, was dramatically increased and showed a linear dependency on the HPCD concentration. The degree of incorporation was 20 mg of 1 per g of complex. The stability study of 1 in various pH buffers indicated the base-catalyzed hydrolysis of the acyloxyalkyl linkage and the hydration of the 5,6 double bond of the dihydropyridine as the main degradation processes. The overall loss of 1, which follows first-order kinetics, was not influenced by changes in ionic strength and elimination of oxygen from the reaction medium. The HPCD complex of 1, which has a stability constant of 720-940 M-1, stabilized the chemical delivery system. The influence of the temperature on the stability of 1 is also discussed.
Pop
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Center for Drug Design and Delivery, College of Pharmacy, University of Florida, J. Hillis Miller Health Center, Gainesville 32610.
Loftsson
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Bodor
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D000073738:2-Hydroxypropyl-beta-cyclodextrin; D003505:Cyclodextrins / Q000008:administration & dosage*; D004337:Drug Carriers; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D010400:Penicillin G / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D013696:Temperature; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D004337:Drug Carriers; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D010400:Penicillin G