Shirsand S B, Suresh Sarasija, Jodhana L S, Swamy P V
Department of Pharmaceutics, H.K.E. Society's College of Pharmacy, Sedam Road, Gulbarga - 585 104, India.
Indian J Pharm Sci. 2010 Jul;72(4):431-6. doi: 10.4103/0250-474X.73911.
Fast disintegrating tablets of lorazepam were prepared by effervescent method with a view to enhance patient compliance. A 3(2) full factorial design was applied to investigate the combined effect of two formulation variables: amount of crospovidone and mixture of sodium bicarbonate, citric acid and tartaric acid (effervescent material) on in vitro dispersion time. Crospovidone (2-8% w/w) was used as superdisintegrant and mixture of sodium bicarbonate, citric acid and tartaric acid (6-18% w/w) was used as effervescent material, along with directly compressible mannitol to enhance mouth feel. The tablets were evaluated for hardness, friability, thickness, drug content uniformity and in vitro dispersion time. Based on in vitro dispersion time (approximately 13 s); the formulation containing 8% w/w crospovidone and 18% w/w mixture of sodium bicarbonate, citric acid and tartaric acid was found to be promising and tested for in vitro drug release pattern (in pH 6.8 phosphate buffer), short-term stability and drug-excipient interaction. Surface response plots are presented to graphically represent the effect of independent variables (concentrations of crospovidone and effervescent material) on the in vitro dispersion time. The validity of the generated mathematical model was tested by preparing two extra-design check point formulations. The optimized tablet formulation was compared with conventional marketed tablet for drug release profiles. This formulation showed nearly eleven-fold faster drug release (t(50%) 2.8 min) compared to the conventional commercial tablet formulation (t(50%) >30 min). Short-term stability studies on the formulation indicated that there were no significant changes in drug content and in vitro dispersion time (P<0.05).
为提高患者顺应性，采用泡腾法制备了劳拉西泮速崩片。采用3(2)全因子设计研究两个处方变量：交联聚维酮用量以及碳酸氢钠、柠檬酸和酒石酸混合物（泡腾材料）对体外分散时间的联合作用。交联聚维酮（2 - 8% w/w）用作超级崩解剂，碳酸氢钠、柠檬酸和酒石酸混合物（6 - 18% w/w）用作泡腾材料，同时加入可直接压片的甘露醇以改善口感。对片剂进行硬度、脆碎度、厚度、药物含量均匀度和体外分散时间的评价。基于体外分散时间（约13秒），发现含8% w/w交联聚维酮和18% w/w碳酸氢钠、柠檬酸和酒石酸混合物的制剂有前景，并对其体外药物释放模式（在pH 6.8磷酸盐缓冲液中）、短期稳定性和药物-辅料相互作用进行了测试。给出表面响应图以直观表示自变量（交联聚维酮和泡腾材料浓度）对体外分散时间的影响。通过制备两个额外设计的检查点制剂来测试所建立数学模型的有效性。将优化后的片剂处方与市售传统片剂的药物释放曲线进行比较。该制剂的药物释放速度比传统市售片剂制剂快近11倍（t(50%) 2.8分钟）（传统市售片剂制剂t(50%) >30分钟）。该制剂的短期稳定性研究表明，药物含量和体外分散时间无显著变化（P<0.05）。
