Gentamycin/poly(lactic acid) blends aimed at sustained release local antibiotic therapy administered per-operatively. I. The case of gentamycin base and Gentamycin sulfate (cas 1405-41-0) in poly(dl-lactic acid) oligomers

Add time:09/26/2019    Source:sciencedirect.com

In an attempt to make gentamycin delivery systems suitable for per-operative local antibiotic therapy, gentamycin base, GB, and Gentamycin sulfate (cas 1405-41-0), GS, were blended with poly (dl-lactic acid) oligomers, PLA50p, dissolved in acetone. Waxy PLA50p oligomers were prepared by step-growth polymerization of dl-lactic acid. After drying, the PLA50p/GS blends led to waxy systems which physically resembled the starting oligomers whereas GB blends appeared as solid particles after grinding. For both types of mixtures, biphasic release profiles were observed in pH = 7.4, 0.13 M phosphate buffer, the first phase corresponding to a fast release which depended on the composition and the chemical form of the drug whereas the second phase corresponded to a period of very slow release. None of the systems exhibited the desired delivery characteristics. From 13C-NMR, FTIR, DSC and assays of gentamycin and l-lactic acid, it was shown that the stabilization of PLA50p and the dependence of the release profiles on the chemical state of the drug and on the composition of PLA50p-gentamycin mixtures were due to acid-base interactions between carboxylic acid end-groups and the cationic antibiotic. It was further shown that in the case of PLA50p/GS systems these interactions did not take place until the mixtures were in contact with an aqueous medium.

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