Thermal Decomposition of Amorphous β-Lactam Antibacterials

doi:10.1002/jps.2600660927

Journal of Pharmaceutical Sciences

Volume 66, Issue 9, September 1977, Pages 1312-1316

https://doi.org/10.1002/jps.2600660927 Get rights and content

Abstract

Thermal decomposition rates for amorphous samples of penicillin G potassium, cephalothin sodium, cefamandole sodium, and cefamandole nafate were determined as a function of water content and temperature. Even when rigorously dry, amorphous cephalosporins were at least one order of magnitude less stable than the corresponding unsolvated crystalline form. Absorbed water generally increased both the number of decomposition products and the net decomposition rate. Reaction kinetics were usually apparent first order, but an anomalously high effective reaction order was observed in several systems. Nonlinear Arrhenius plots were observed, and a qualitative model based on molecular relaxation in glasses is proposed. Although decomposition rates at 25° were small for dry samples, even slight decomposition produced visually detectable changes. Thus, the unsolvated crystalline form was noticeably more stable, even at 25°.

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: The authors thank the members of the Analytical Chemistry Groups at Eli Lilly and Co. for performing the assay work. They also thank Mr. K. S. Yang, Dr. S. Schildcrout, and Dr. L. Tensmeyer for providing samples of cephalosporins.

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Research ArticlesThermal Decomposition of Amorphous β-Lactam Antibacterials

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Thermal Decomposition of Amorphous β-Lactam Antibacterials