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原位形成的缓释注射剂及其在兽用产品中的潜在用途。

Sustained-release injectables formed in situ and their potential use for veterinary products.

作者信息

Matschke Christian, Isele Ute, van Hoogevest Peter, Fahr Alfred

机构信息

Novartis Animal Health Inc, Schwarzwaldallee 215, CH-4002, Basel, Switzerland.

出版信息

J Control Release. 2002 Dec 13;85(1-3):1-15. doi: 10.1016/s0168-3659(02)00266-3.

Abstract

The controlled drug delivery of hydrophilic and lipophilic drug substances via the parenteral route has gained increasing importance in the development of pharmaceutical dosage forms. In particular, the animal health industry has generated strong interest in long-term drug delivery for both companion and farm animals during the past few years. At present sustained-release injectables formed in situ for s.c./i.m. administration have become an attractive alternative to common slow release technologies such as microspheres or standard implants. In this context, technologies based on PLA/PLGA, sucrose acetate isobutyrate (SAIB) and the amphipathic molecules Poloxamer, glycerol monooleate or PEG-PLA-PEG copolymers, are discussed. Release periods from hours to months can be obtained by choosing one of these drug delivery technologies. The release times are strongly dependent on the biodegradation of the polymers and the physico-chemical properties of the drug substance used. Furthermore, the use of different solvents for the matrix-forming agents and the individual loading capacity are critically assessed. Additionally acceptance of the excipients for parenteral use by the regulatory authorities is closely considered. Scientific articles as well as patent publications are reviewed to give a wide overview of the existing approaches and their future potential for animal health products.

摘要

通过非肠道途径对亲水性和疏水性药物进行可控给药,在药物剂型开发中变得越来越重要。特别是在过去几年中,动物保健行业对伴侣动物和农场动物的长期给药产生了浓厚兴趣。目前,用于皮下/肌肉注射给药的原位形成的缓释注射剂已成为微球或标准植入物等常见缓释技术的有吸引力的替代方案。在此背景下,讨论了基于聚乳酸/聚乳酸-羟基乙酸共聚物(PLA/PLGA)、醋酸异丁酸蔗糖酯(SAIB)以及两亲性分子泊洛沙姆、单油酸甘油酯或聚乙二醇-聚乳酸-聚乙二醇共聚物(PEG-PLA-PEG)的技术。通过选择这些药物递送技术之一,可以获得从数小时到数月的释放期。释放时间强烈依赖于聚合物的生物降解以及所用药物的物理化学性质。此外,还对用于基质形成剂的不同溶剂的使用和个体载药量进行了严格评估。另外,还密切考虑了监管机构对非肠道用辅料的接受情况。对科学文章和专利出版物进行了综述,以广泛概述现有方法及其在动物保健产品方面的未来潜力。

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