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.
Keywords: Bioavailability; HPMC E-5; High pressure homogenizer; Pharmacokinetic modeling; Satranidazole; Span 20.
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