盐酸二甲胺四环素用于牙周炎的缓释原位凝胶新剂型的研究

Investigation on a new sustained release in-situ gel dosage form of minomycin hydrochloride for periodontitis

目的以盐酸二甲胺四环素(MINO·HCl)为模型药物,制备一种可通过针头注射到牙周袋内,在牙周袋内发生相转变形成凝胶,可持续稳定地缓慢释放药物的原位凝胶剂型。方法试验透明质酸(HA)及共聚物的溶解情况,对不同组分制成的原位凝胶进行通针性和凝固情况考察,选择共聚物和有机溶剂。制备MINO·HCl缓释原位凝胶进行质量评价,观察外观形态,通针性情况,并测定黏度。测定MINO·HCl的含量,研究原位凝胶的体外释放。结果选择以聚乳酸-羟基乙酸共聚物(PLGA50∶50)为基质,N-甲基吡咯烷酮(NMP)为溶剂,N-乙烯基吡咯烷酮(NVP)为助溶剂,处方成分包括:PLGA50∶50、NMP、NVP、HA、MINO·HCl。MINO·HCl缓释原位凝胶的外观为棕色透明,并且通针性和流动性较好。采用紫外分光光度法测得MINO·HCl的含量合格。在37℃条件下,制备的缓释原位凝胶在第1天有37.40%的快速释放,之后便可稳定持续地释放药物,在第7天累积释放达到90.53%。结论以PLGA50∶50、HA、NMP和NVP为辅料制备了可持续稳定地缓慢释放药物的MINO·HCl缓释原位凝胶。

Objective With minomycin hydrochloride(MINO·HCl)as the model drug,to prepare an in-situ gel dosage form,which could be injected into the periodontal pocket through a needle,so as to form the gel in the periodontal pocket,and to release the drug slowly,steadily and continuously.Methods The dissolution of hyaluronic acid(HA)and copolymer was tested,the needle penetration and solidification of in-situ gel made of different components were investigated,and the copolymer and organic solvent were selected.MINO·HCl sustained release in-situ gel was prepared for quality evaluation,and its appearance and needle penetration were observed,and the viscosity was measured.The content of MINO·HCl was measured,and the release of in-situ gel in vitro was investigated.Results Copolymer of polylactic acid and glycolic acid(PLGA50∶50)was selected as matrix,N-methylpyrrolidone(NMP)was selected as the solvent and N-vinylpyrrolidone(NVP)was selected as the cosolvent.The ingredients of the prescription include:PLGA50∶50,NMP,NVP,HA and MINO·HCl.The appearance of MINO·HCl sustained release in-situ gel was brown and transparent,and it had relatively good needle penetration and fluidity.The content of MINO·HCl determined by ultraviolet spectrophotometry was qualified.At 37℃,the prepared sustained release in-situ gel released 37.40%rapidly on the first day,then released the drug steadily and continuously,and the cumulative release reached 90.53%on the seventh day.Conclusion MINO·HCl sustained release in-situ gel,which is prepared with PLGA50∶50,HA,NMP and NVP as auxiliary materials,can release the drug slowly,steadily,and continuously.