Preparation, characterization and pharmacokinetic study of nelfinavir nanocrystals for oral bioavailability enhancement

The study is aimed at development of nanocrystals of Nelfinavir Mesylate, an anti-HIV drug to overcome the drawback associated with drug such as poor solubility and oral bioavailability. Nanocrystals were attempted by combination technique and ultrasonication method using polyvinyl alcohol (PVA) and poloxamer 407 as stabilizers at various concentrations. The solid-state characteristics of optimized nanocrystals were studied by XRD, FTIR, DSC and SEM analysis. The release behavior of the drug was studied by in vitro dissolution. The in vivo pharmacokinetics was assessed in Wister Albino rats by administering nanocrystals orally. Nelfinavir nanocrystals were obtained with the narrow size distribution and mean particle size was ranged from 216 to 360 nm for the nanocrystals obtained from combination technique. At 0.5% w/w of PVA, particle size was 236 ± 19.23 nm and zeta potential was 18.34 ± 2.0 mV. Freeze dried Poloxamer 407 and PVA nanocrystals showed very good solubility than the freeze dried powder with cryoprotectant and pure drug. However, nanocrystals with PVA (NC PVA) showed high dissolution velocity as compared to nanocrystals with Poloxamer 407 and were supported by high saturation solubility of NC PVA. SEM and other solid-state studies indicated the crystalline nature of developed nanocrystals. Compared to pure drug, NC PVA formulation had decreased T_max and increased C_max and AUC_0-24. Thus pharmacokinetic study revealed significant increase in oral absorption of the drug with nanocrystals which could be attributed to the increase in dissolution velocity of the Nelfinavir in nanocrystal form.