塞硝唑原位凝胶治疗牙周病的制备及体外评价

Dheyaa A Raheema, H. Kassab
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摘要

本研究旨在开发一种用于治疗牙周炎的塞克硝唑局部释放药物的热敏黏附牙周原位凝胶,以增加药物停留时间,提高患者的依从性,同时降低药物的副作用。用不同浓度的热敏聚合物(poloxamer407单独或与poloxamer188联合使用)和不同浓度的甲基纤维素(MC)或羟丙基甲基纤维素(HPMC K4M)作为粘接聚合物,采用冷法制备了30个塞克硝唑牙周原位凝胶配方,并对所得到的配方进行了胶凝温度GT、外观和pH值等测试。采用体外释药试验对最合适的GT配方进行了体外释药试验。选择释放度合适的配方F6 (15% P407, 1% MC)、F29 (18%P407,3% P188, 0.8% HPMC)和F30 (18%P407,3% P188, 1% HPMC)。对这些配方进行了粘接力、粘度、药物含量、涂敷性、胶凝时间和傅里叶变换红外(FTIR)相容性研究。结果表明,配方F29和F30的最佳胶凝温度(33℃、32℃)、胶凝强度(1.5h、2h)、黏结力(17.1、23.4达因/cm2)和体外释药率(98.2%、100%)分别为3.5h和胶凝时间(约10 s), FTIR光谱研究表明,两种配方与聚合物之间不存在重要的相互作用。
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Preparation and in-vitro Evaluation of Secnidazole as Periodontal In-situ Gel for Treatment of Periodontal Disease
This study aims to develop a thermosensitive mucoadhesive periodontal in situ gel of secnidazole for local release of drug for treatment of periodontitis, in order to increase the drug residence time and to increase patient compliance while lowering the side effects of the drug. Cold method was used to prepare 30 formulas of secnidazole periodontal in situ gel, using different concentrations of thermosensitive polymers (poloxamer407 alone or in combination with poloxamer 188) and methyl cellulose (MC ) or hydroxypropyl methylcellulose (HPMC K4M )in different concentrations used as mucoadhesive polymer and the resultant formulations were subjected to several tests such as   gelation temperature GT, appearance and pH value. The formulas with the most appropriate GT were subjected to in-vitro drug release. Three formulas were chosen with appropriate release, F6 (15% P407, 1% MC), F29 (18%P407,3% P188, 0.8% HPMC) and F30 (18%P407,3% P188, 1% HPMC). These formulas were subjected to mucoadhesive force, viscosity, drug content, spreadability, gelation time and Fourier Transform Infrared (FTIR) compatibility studies. The results indicates that formula F29 and F30 have best gelation temperatures (33°C, 32°C) gel strength (1.5h,2h) mucoadhesive force of (17.1, 23.4 dyne/cm2 ) and in-vitro drug release (98.2%, 100%) respectively during 3.5h and gelation, time about 10 seconds for both formulas and FTIR spectrum study show absence of important interaction between secnidazole and the polymers used.
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