Hiremath Praveen S, Saha Ranendra N
Pharmacy Group, Birla Institute of Technology and Science, Pilani, Rajasthan, India.
Int J Pharm. 2008 Oct 1;362(1-2):118-25. doi: 10.1016/j.ijpharm.2008.06.019. Epub 2008 Jul 3.
The aim of the present investigation was to develop controlled release (C.R.) matrix tablet formulations of rifampicin and isoniazid combination, to study the design parameters and to evaluate in vitro release characteristics. In the present study, a series of formulations were developed with different release rates and duration using hydrophilic polymers hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC). The duration of rifampicin and isoniazid release could be tailored by varying the polymer type, polymer ratio and processing techniques. Further, Eudragit L100-55 was incorporated in the matrix tablets to compensate for the pH-dependent release of rifampicin. Rifampicin was found to follow linear release profile with time from HPMC formulations. In case of formulations with HPC, there was an initial higher release in simulated gastric fluid (SGF) followed by zero order release profiles in simulated intestinal fluid (SIFsp) for rifampicin. The release of isoniazid was found to be predominantly by diffusion mechanism in case of HPMC formulations, and with HPC formulations release was due to combination of diffusion and erosion. The initial release was sufficiently higher for rifampicin from HPC thus ruling out the need to incorporate a separate loading dose. The initial release was sufficiently higher for isoniazid in all formulations. Thus, with the use of suitable polymer or polymer combinations and with the proper optimization of the processing techniques it was possible to design the C.R. formulations of rifampicin and isoniazid combination that could provide the sufficient initial release and release extension up to 24h for both the drugs despite of the wide variations in their physicochemical properties.
本研究的目的是开发利福平与异烟肼复方控释（C.R.）骨架片制剂，研究设计参数并评估其体外释放特性。在本研究中，使用亲水性聚合物羟丙基甲基纤维素（HPMC）和羟丙基纤维素（HPC）开发了一系列具有不同释放速率和持续时间的制剂。利福平和异烟肼的释放持续时间可通过改变聚合物类型、聚合物比例和加工工艺来调整。此外，将Eudragit L100 - 55加入骨架片中以补偿利福平的pH依赖性释放。发现利福平从HPMC制剂中随时间呈线性释放曲线。对于含HPC的制剂，利福平在模拟胃液（SGF）中最初有较高释放，随后在模拟肠液（SIFsp）中呈零级释放曲线。在HPMC制剂中，异烟肼的释放主要通过扩散机制，而在HPC制剂中，释放是扩散和侵蚀共同作用的结果。利福平从HPC中的初始释放足够高，因此无需加入单独的负荷剂量。所有制剂中异烟肼的初始释放都足够高。因此，通过使用合适的聚合物或聚合物组合，并对加工工艺进行适当优化，尽管利福平和异烟肼的理化性质差异很大，但仍有可能设计出能为两种药物提供足够初始释放并将释放延长至24小时的利福平与异烟肼复方控释制剂。
