Evaluation of the impact of the polymer end groups and molecular weight on in vitro and in vivo performances of PLGA based in situ forming implants for ketoprofen.

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Journal of pharmaceutical sciences Pub Date : 2024-10-18 DOI:10.1016/j.xphs.2024.10.019
Sanjib Saha, Xinhao Lin, Liping Zhou, Aixiang Xue, Eric Gosselin, Paresh P Chothe, Mittal Darji, Xiuling Lu, Wenzhan Yang
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Abstract

In situ forming implants are appealing long-acting dosage forms for both preclinical and clinical applications due to their simple manufacturing process and easy delivery. This study aims to develop extended-release in situ forming solid implants for subcutaneous administration using two types of commercially available triblock poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA) polymers, with either an acid or ester end group. Both types of polymers instantly form in situ implants when injected directly into an aqueous medium. The performance of these implants, containing a model compound ketoprofen, was evaluated by comparing the in vitro drug release profiles with the in vivo performance following subcutaneous administration in rats. Analytical characterizations of two representative in situ implants were conducted to understand their structural impact on polymer degradation and drug release. All tested in situ forming implants demonstrated prolonged drug release profiles both in vitro and in vivo. This study illustrates the successful preparation of sustained-release in situ forming implant formulations for ketoprofen using commercially available polymers, with the molecular weight and the end group of the polymers affecting their degradation and the drug release from the in situ formed implants.

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评估聚合物端基和分子量对基于 PLGA 的酮洛芬原位成型植入物的体外和体内性能的影响。
原位成型植入物因其生产工艺简单、给药方便而成为临床前和临床应用中极具吸引力的长效剂型。本研究旨在开发用于皮下给药的缓释原位成型固体植入物,使用两种市售的三嵌段聚(乳酸-聚乙二醇)-聚(乳酸-聚乙二醇-聚乳酸)(PLGA-PEG-PLGA)聚合物,其端基均为酸或酯。这两种聚合物直接注入水介质后,可立即形成原位植入体。通过比较体外药物释放曲线和大鼠皮下注射后的体内表现,评估了这些含有模型化合物酮洛芬的植入物的性能。对两种具有代表性的原位植入物进行了分析,以了解其结构对聚合物降解和药物释放的影响。所有接受测试的原位成型植入物在体外和体内都表现出较长的药物释放曲线。这项研究表明,使用市售聚合物可以成功制备酮洛芬的原位成型缓释植入剂配方,聚合物的分子量和端基会影响其降解和原位成型植入剂的药物释放。
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来源期刊
CiteScore
7.30
自引率
13.20%
发文量
367
审稿时长
33 days
期刊介绍: The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.
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