School of Pharmacy, International Medical University, 57000, Bukit Jalil, Kuala Lumpur, Malaysia.
Department of Pharmaceutics, Faculty of Pharmacy, Universiti Teknologi MARA Selangor, Puncak Alam Campus, 42300, Puncak Alam, Kuala Selangor, Malaysia.
Drug Deliv Transl Res. 2019 Apr;9(2):534-542. doi: 10.1007/s13346-018-0491-y.
The objectives of this study were to develop biodegradable poly-lactic-co-glycolic acid (PLGA) based injectable phase inversion in situ forming system for sustained delivery of triamcinolone acetonide (TA) and to conduct physicochemical characterisation including in vitro drug release of the prepared formulations. TA (at 0.5%, 1% and 2.5% w/w loading) was dissolved in N-methyl-2-pyrrolidone (NMP) solvent and then incorporated 30% w/w PLGA (50/50 and 75/25) polymer to prepare homogenous injectable solution. The formulations were evaluated for rheological behaviour using rheometer, syringeability by texture analyser, water uptake and rate of implant formation by optical coherence tomography (OCT) microscope. Phase inversion in situ forming formulations were injected into PBS pH 7.3 to form an implant and release samples were collected and analysed for drug content using a HPLC method. All formulations exhibited good syringeability and rheological properties (viscosity: 0.19-3.06 Pa.s) by showing shear thinning behaviour which enable them to remain as free-flowing solution for ease administration. The results from OCT microscope demonstrated that thickness of the implants were increased with the increase in time and the rate of implant formation indicated the fast phase inversion. The drug release from implants was sustained over a period of 42 days. The research findings demonstrated that PLGA/NMP-based phase inversion in situ forming implants can improve compliance in patient's suffering from ocular diseases by sustaining the drug release for a prolonged period of time and thereby reducing the frequency of ocular injections.
本研究的目的是开发可生物降解的聚乳酸-共-乙醇酸(PLGA)基可注射相转化原位形成系统,用于持续释放曲安奈德(TA),并对制剂进行物理化学特性包括体外药物释放的研究。将 TA(0.5%、1%和 2.5%w/w 负载量)溶解在 N-甲基-2-吡咯烷酮(NMP)溶剂中,然后加入 30%w/w 的 PLGA(50/50 和 75/25)聚合物,制备均匀的可注射溶液。使用流变仪评估制剂的流变行为,使用质构分析仪评估可注射性,使用光学相干断层扫描(OCT)显微镜评估水吸收和植入物形成速度。将相转化原位形成的制剂注入 PBS pH 7.3 中形成植入物,并收集释放样品,使用 HPLC 方法分析药物含量。所有制剂均表现出良好的可注射性和流变性能(粘度:0.19-3.06 Pa.s),表现出剪切稀化行为,使其能够保持为自由流动的溶液,便于给药。OCT 显微镜的结果表明,植入物的厚度随时间的增加而增加,植入物形成的速度表明快速相转化。药物释放可在 42 天内持续释放。研究结果表明,基于 PLGA/NMP 的相转化原位形成植入物可通过延长药物释放时间来提高患有眼部疾病的患者的顺应性,从而减少眼部注射的频率。