Dhat Shalaka, Pund Swati, Kokare Chandrakant, Sharma Pankaj, Shrivastava Birendra
School of Pharmaceutical Sciences, Jaipur National University, Jaipur 302 017, Rajasthan, India; Department of Pharmaceutics, STES's Sinhgad Institute of Pharmacy (Affiliated to Savitribai Phule Pune University), Narhe, Pune 411 041, Maharashtra, India.
Department of Pharmaceutics, STES's Sinhgad Institute of Pharmacy (Affiliated to Savitribai Phule Pune University), Narhe, Pune 411 041, Maharashtra, India.
Eur J Pharm Biopharm. 2016 Mar;100:109-18. doi: 10.1016/j.ejpb.2015.12.007. Epub 2015 Dec 31.
The designing of surface engineered nanocrystals for improved stability and bioavailability is a multivariate process depending on several critical formulation and process variables. The present investigation deals with formulation of stable nanocrystals of poorly soluble satranidazole (SAT) for improving dissolution rate and pharmacokinetic profiling. SAT has low polar surface area, high dose and dosing frequency. Based on goniometric and stability studies of formulations prepared with various stabilizers, a unique combination of Span 20 and HPMC E-5 was selected for detailed investigation. Lyophilization of SAT nanosuspension was explored with nine different cryoprotectants in varying amounts to obtain easily redispersible nanocrystals (SAT-NC). The mean particle size and zeta potential of SAT-NC were found to be 208.8nm and -41.3mV respectively. DSC and XRPD confirmed the crystalline state of SAT. In vitro release studies of SAT-NC showed almost complete dissolution within 20min in water. Extravascular, one compartment pharmacokinetic modeling of in vivo plasma concentration versus time studies in male Wistar rats revealed twofold increase in Cmax, and AUC0-∞. Method of residuals was employed to calculate rate of absorption Ka and lag time. Nanosizing with appropriate stabilizers and programmed processing conditions successfully produced SAT-NC with improved pharmaceutic and pharmacokinetic characteristics.
设计具有更高稳定性和生物利用度的表面工程纳米晶体是一个多变量过程，它取决于几个关键的制剂和工艺变量。本研究旨在制备难溶性沙硝唑（SAT）的稳定纳米晶体，以提高其溶出速率并优化药代动力学特征。SAT具有低极性表面积、高剂量和给药频率。基于对用各种稳定剂制备的制剂的测角和稳定性研究，选择了Span 20和羟丙甲纤维素E-5的独特组合进行详细研究。用九种不同用量的冷冻保护剂探索了SAT纳米混悬液的冻干过程，以获得易于再分散的纳米晶体（SAT-NC）。发现SAT-NC的平均粒径和zeta电位分别为208.8nm和-41.3mV。差示扫描量热法（DSC）和X射线粉末衍射（XRPD）证实了SAT的结晶状态。SAT-NC的体外释放研究表明，其在水中20分钟内几乎完全溶解。在雄性Wistar大鼠体内进行的血浆浓度与时间关系的血管外单室药代动力学建模显示，Cmax和AUC0-∞增加了两倍。采用残差法计算吸收速率常数Ka和滞后时间。使用合适的稳定剂进行纳米化处理并采用程序化的加工条件，成功制备出了具有改善的药学和药代动力学特性的SAT-NC。
