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Leuprolide Acetate Release Study from γ-Irradiated PLGA-based In Situ Forming System

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Background: It is well known that the properties of polymers can be altered by exposure to γ- ray. γ-irradiation has been used as a sterilization method for polymeric drug delivery devices, and its drug release profile must not be significantly changed. In this study, the effect of γ-irradiation on the release profile of leuprolide acetate from PLGA-based in situ forming system was investigated.

Methods: Poly(lactide-co-glycolide) (PLGA) was dissolved in N-methylpyrrolidinone (NMP) and irradiated with a total dose of 8 kGy γ-ray emitted by a 60Co source. Then, leuprolide acetate was added to the polymer solution. PLGA-based in situ forming systems were prepared by injecting some specific amount of prepared solution into a buffer phosphate pH 7.4 at 37 °C. The effects of γ-ray on drug release profiles, morphology of matrices and thermal properties as well as stability of polymer were evaluated.

Results: The results showed that γ-irradiation causes a decrease in glass transition temperature (Tg) of PLGA from 43.4 to 38.1°C. A reduction in molecular weight of PLGA by about 17.8 % was found as consequence of radiolytic degradation. The morphological studies of PLGA matrices confirmed that the irradiated sample had higher porosity than the non-irradiated sample. It is found that the amount of released leuprolide acetate from irradiated matrix was increased by about 1.6 times after 33 days compared to the nonirradiated ones. In vitro drug release experimental data were fitted using the Gallagher- Corrigan model which indicated that diffusion and degradation were the predominant mechanisms of drug release.

Conclusion: Accordingly, leuprolide acetate was released faster from the irradiated matrix compared to the non- irradiated matrix.
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Keywords: Gallagher-Corrigan model; In situ forming systems; fibroids; leuprolide acetate; poly(lactide-co-glycolide); γ-irradiation

Document Type: Research Article

Publication date: December 1, 2017

This article was made available online on August 21, 2017 as a Fast Track article with title: "Leuprolide Acetate Release Study from γ-Irradiated PLGA-based In Situ Forming System".

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  • The aim of Current Drug Delivery is to publish peer-reviewed articles, short communications, short and in-depth reviews in the rapidly developing field of drug delivery. Modern drug research aims to build in delivery properties of a drug at the design phase, however in many cases this ideal cannot be met and the development of delivery systems becomes as important as the development as the drugs themselves.

    The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance.

    The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.
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