坎地沙坦西莱西酯速溶片的升华法制备及研究

Hunashal Sarah Priya, B. Patil, Ravindra S. Jeevanagi
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引用次数: 1

摘要

坎地沙坦西列地酯是坎地沙坦的前药,坎地沙坦是一种抑制血管紧张素II与AT1受体结合的化合物。主要用于治疗高血压。本文尝试用升华法制备坎地沙坦西莱西酯速溶片。对制备的配方进行了压缩前和压缩后参数的评价。用FTIR研究了药物与其它辅料的配伍性,结果表明,与其它辅料之间没有相互作用。压缩前参数值在规定范围内,表现出良好的自由流动特性。在所有配方中,硬度试验表明机械强度好。所有配方的脆性均小于1。各制剂中药物含量高(≥100.27%)且均匀。片剂厚度为3.14 ~ 3.47。重量变化结果表明,各配方的平均偏差小于±7.5%,具有较好的均匀性。随着升华剂浓度的增加,片剂的崩解时间明显缩短。制剂CSC3、CSM3、CSA3、CSU3在1.38、2.55、4.00、3.57 min的释药时间为50%,在3.39、6.04、7.50、7.18 min的释药时间为90%。对照制剂CS在60 min的释药时间为42.16%。按照ICH指南进行了为期3个月的稳定性研究,结果表明:贮存后崩解时间显著缩短(p<0.05)。结果表明,采用系统制定方法可以在最短的时间内以最小的努力达到最优点。与在速溶片剂配方中使用更昂贵的佐剂相比,升华技术将是一种有效的替代方法。
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Formulation and Development of Candesartan Cilexetil Fast Dissolving Tablets by Sublimation Technique
Candesartan cilexetil is a prodrug of candesartan – a compound that inhibits binding of angiotensin II to the AT1 – receptor. It is mainly used in the treatment of hypertension. In the present work attempts were mase to prepare fast dissolving tablets of candesartan cilexetil by sublimation technique. The prepared formulations were evaluated for pre-compressional and postcompressional parameters. The compatibility of drug with other ingredients was checked by FTIR studies, these results revealed that there was no interaction between dug and other excipients. The values of pre-compressional parameters were within prescribed limits and indicated good free flowing properties. In all the formulations the hardness test indicates good mechanical strength. Friability of all formulations was less than 1. Drug content was found to be high (≥ 100.27%) and uniform in all the formulations. The tablet thickness was found to be 3.14 – 3.47. The weight variation results revealed that average percentage deviation was less then ± 7.5 %, which provides good uniformity in all formulations. The disintegration time of the tablets decreased significantly with increase in the concentration of subliming agent. The formulations CSC3, CSM3, CSA3, and CSU3 50 % of drug released in 1.38, 2.55, 4.00 and 3.57 min, and 90 % of drug released in 3.39, 6.04, 7.50 and 7.18 min. The formulation CS (control) released 42.16 % in 60 min. Stability study carried out as per ICH guidelines for three months and results revealed that upon storage disintegration time of tablets decreased significantly (p<0.05). The results concluded that by adopting a systemic formulation approach, an optimum point could be reached in the shortest time with minimum efforts. Sublimation technique would be an effective alternative approach compared with the use of more expensive adjuvants in the formulations of fast dissolving tablets.
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