Chavanpatil Mahesh, Jain Paras, Chaudhari Sachin, Shear Rajesh, Vavia Pradeep
Mumbai University Institute of Chemical Technology, Pharmaceutical Sciences Division, Near Nathalal Parikh Marg, Matunga, Mumbai 400019, India.
Int J Pharm. 2005 Nov 4;304(1-2):178-84. doi: 10.1016/j.ijpharm.2005.08.009. Epub 2005 Sep 29.
Sustained release (SR)-gastroretentive dosage forms (GRDF) enable prolonged and continuous input of the drug to the upper parts of the gastrointestinal (GI) tract and improve the bioavailability of medications that are characterized by a narrow absorption window. A new strategy is proposed for the development of gastroretentive dosage forms for ofloxacin preferably once daily. The design of the delivery system was based on the sustained release formulation, with floating and swelling features in order to prolong the gastric retention time of the drug delivery systems. Different polymers, such as psyllium husk, HPMC K100M, crospovidone and its combinations were tried in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for buoyancy lag time, duration of buoyancy, dimensional stability, drug content and in vitro drug release profile. It was found that dimensional stability of the formulation increases with the increasing psyllium husk concentration. It was also found that in vitro drug release rate increased with increasing amount of crospovidone due to the increased water uptake, and hence increased driving force for drug release. The optimized formulation was subjected to stability studies at different temperature and humidity conditions as per ICH guidelines. In vivo studies were carried out for the optimized formulation in 24 healthy human volunteers and the pharmacokinetic parameters of developed formulations were compared with the marketed once daily (Zanocin) formulation. Based on the in vivo performance in a parallel study design in healthy subjects, the developed formulation shows promise to be bioequivalent to the marketed product (Zanocin). The percent relative bioavailability of developed formulation was found to be 97.55%.
缓释（SR）胃滞留剂型（GRDF）能够使药物持续不断地输入到胃肠道（GI）上部，并提高具有窄吸收窗药物的生物利用度。本文提出了一种新策略，用于开发氧氟沙星胃滞留剂型，最好是每日一次给药。该给药系统的设计基于缓释制剂，具有漂浮和溶胀特性，以延长药物递送系统的胃滞留时间。尝试了不同的聚合物，如车前子壳、羟丙甲纤维素K100M、交联聚维酮及其组合，以在24小时内获得所需的缓释曲线。对各种制剂进行了浮力滞后时间、浮力持续时间、尺寸稳定性、药物含量和体外药物释放曲线的评估。发现制剂的尺寸稳定性随着车前子壳浓度的增加而提高。还发现，由于吸水量增加，体外药物释放速率随着交联聚维酮用量的增加而提高，从而增加了药物释放的驱动力。根据ICH指南，对优化后的制剂在不同温度和湿度条件下进行稳定性研究。在24名健康人类志愿者中对优化后的制剂进行了体内研究，并将所开发制剂的药代动力学参数与市售的每日一次（Zanocin）制剂进行了比较。基于在健康受试者中平行研究设计的体内性能，所开发的制剂显示出与市售产品（Zanocin）生物等效的前景。所开发制剂的相对生物利用度百分比为97.55%。
