Bhise S B, Rajkumar M
Biopharmaceutical Research Group, Department of Biopharmaceutics, Govt. College of Pharmacy, Karad, India.
PDA J Pharm Sci Technol. 2010 Jan-Feb;64(1):28-36.
The dissolution behavior and bioavailability of carbamazepine (CBZ) is rate-limited by formation of carbamazepine dihydrate (CBZ-D) in dissolution fluids. The present investigation involves formation and biopharmaceutical evaluation of CBZ-D obtained from simulated gastrointestinal fluids. The results obtained from solubility studies revealed that formation of CBZ-D was pH-dependent. The minimum solubility of 115 ± 1.7 mg/L obtained with simulated gastric fluid without pepsin indicates that the strongly acidic pH favors formation of CBZ-D and it was confirmed by the powder X-ray diffractography. Differential scanning calorimetry thermograms of samples revealed formation of CBZ-D and subsequent transition of CBZ form I. The percentage relative crystallinty for dihydrate was found to be 77.51%. Triton X present in fasted-state simulated gastric fluid (FaSSGF) increased the extent of crystallinty in dissolution media upto 86.50%. However, CBZ-D obtained from FaSSGF showed highest solubility of 335.36 ± 4.813 mg/L and dissolution of 36.74% in 60 min. This may be due to presence of surfactant on the surface of CBZ-D. The linear correlation was established between pH of simulated gastrointestinal fluids and percentage relative crystallinty with a correlation coefficient of 0.9904. CBZ form I had a better dissolution profile than any of the other polymorphs. Stabilization of CBZ form I in in vitro and in vivo conditions using pharmaceutical polymers in dosage form may bring better clinical outcomes than present-day therapies.
卡马西平（CBZ）的溶解行为和生物利用度受其在溶解液中形成二水合卡马西平（CBZ-D）的速率限制。本研究涉及从模拟胃肠液中获得的CBZ-D的形成及其生物药剂学评价。溶解度研究结果表明，CBZ-D的形成与pH值有关。在不含胃蛋白酶的模拟胃液中获得的最低溶解度为115±1.7mg/L，这表明强酸性pH值有利于CBZ-D的形成，粉末X射线衍射分析证实了这一点。样品的差示扫描量热法热谱图显示形成了CBZ-D以及随后CBZ晶型I的转变。发现二水合物的相对结晶度百分比为77.51%。禁食状态模拟胃液（FaSSGF）中存在的吐温X使溶解介质中的结晶度程度增加至86.50%。然而，从FaSSGF获得的CBZ-D显示出最高溶解度为335.36±4.813mg/L，在60分钟内的溶出度为36.74%。这可能是由于CBZ-D表面存在表面活性剂。在模拟胃肠液的pH值与相对结晶度百分比之间建立了线性相关性，相关系数为0.9904。CBZ晶型I的溶出曲线比任何其他多晶型物都要好。在剂型中使用药用聚合物在体外和体内条件下稳定CBZ晶型I可能比目前的治疗方法带来更好的临床结果。
