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Solubilization and Stabilization of a Benzylpenicillin Chemical Delivery System by 2-Hydroxypropyl-β-cyclodextrin

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Abstract

A dihydropyridine ↔ pyridinium salt redox carrier-based chemical delivery system for benzylpenicillin (1) was complexed with 2-hydroxypropyl-β-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.

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Authors and Affiliations

  1. Center for Drug Design and Delivery, College of Pharmacy, University of Florida, J. Hillis Miller Health Center, P.O. Box BJ-497, Gainesville, Florida, 32610

    Emil Pop & Nicholas Bodor

  2. Pharmatec, Inc., P.O. Box 730, Alachua, Florida, 32615

    Emil Pop & Nicholas Bodor

  3. Department of Pharmacy, University of Iceland, IS-101, Reykjavik, Iceland

    Thorsteinn Loftsson

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  1. Emil Pop
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  2. Thorsteinn Loftsson
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  3. Nicholas Bodor
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Pop, E., Loftsson, T. & Bodor, N. Solubilization and Stabilization of a Benzylpenicillin Chemical Delivery System by 2-Hydroxypropyl-β-cyclodextrin. Pharm Res 8, 1044–1049 (1991). https://doi.org/10.1023/A:1015865209874

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