Department of Pharmaceutics and Pharmaceutics & Pharmaceutical Technology, University of Lagos, Lagos, Nigeria.
UCL School of Pharmacy, University College London, 29-39, Brunswick Square, London WC1N 1AX, United Kingdom; School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, United Kingdom.
Eur J Pharm Biopharm. 2023 Mar;184:36-49. doi: 10.1016/j.ejpb.2023.01.007. Epub 2023 Jan 13.
In situ gelling formulations are drug delivery systems which typically exist in a liquid form at room temperature and change into gel state after application to the body in response to various stimuli such as changes in temperature, pH and ionic composition. Their biomedical application can further be improved by incorporating drug nanoparticles into in situ gelling systems in order to prolong drug release, reduce dosing frequency and improve therapeutic outcomes of patients, developing highly functional but challenging dosage forms. The composition of in situ gelling formulations influence factors relating to performance such as their syringeability, rheology, drug release profile and drug bioavailability at target sites, amongst other factors. The inclusion of mucoadhesive polymeric constituents into in situ gelling formulations has also been explored to ensure that the therapeutic agents are retained at target site for extended period of time. This review article will discuss traditional techniques (water bath-based vial inversion and viscometry) as well as advanced methodology (rheometry, differential scanning calorimetry, Small Angle Neutron Scattering, Small Angle X-ray Scattering, etc.) for evaluating in situ gel forming systems for topical drug delivery. The clinical properties of in situ gelling systems that have been studied for potential biomedical applications over the last ten years will be reviewed to highlight current knowledge in the performance of these systems. Formulation issues that have slowed the translation of some promising drug formulations from the research laboratory to the clinic will also be detailed.
原位凝胶制剂是一种药物传递系统,通常在室温下以液态形式存在,在施用于人体后会响应各种刺激(如温度、pH 值和离子组成的变化)转变为凝胶状态。通过将药物纳米颗粒纳入原位凝胶系统,可以进一步改善其生物医学应用,以延长药物释放、减少给药频率并改善患者的治疗效果,开发出高功能但具有挑战性的剂型。原位凝胶制剂的组成会影响其性能,如可注射性、流变学、药物释放曲线和药物在靶部位的生物利用度等因素。将具有黏膜粘附性的聚合物成分纳入原位凝胶制剂中也已经被探索,以确保治疗剂在靶部位保持较长时间的滞留。本文将讨论传统技术(水浴瓶倒置和黏度计)以及先进方法(流变学、差示扫描量热法、小角中子散射、小角 X 射线散射等),用于评估用于局部药物递送的原位凝胶形成系统。本文还将综述过去十年中研究用于潜在生物医学应用的原位凝胶系统的临床特性,以突出这些系统性能的现有知识。本文还将详细介绍一些减缓一些有前途的药物制剂从研究实验室向临床转化的配方问题。
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