A spray dried Nelfinavir Mesylate particles for enhanced oral bioavailability: Systematic formulation optimization...

The current endeavor was aimed to fabricate spray dried Nelfinavir Mesylate particles (SDNPs) that upon reconstitution with body fluids releases amorphous Nelfinavir Mesylate with enhanced oral bioavailability. For this purpose, feed mixture was prepared containing solubilized NFM, solid substrate and solvent system. The NFM was solubilized in a mixture of Maisine 35-1 (200 mg), Tween80 (500 mg) and Transcutol HP (300 mg). Three different solid substrates with high specific surface area were used: Neusilin® UFL2, (magnesium aluminometasilicate), Aerosil 200® (colloidal silica) and Syloid 244 FP® (porous silicon dioxide). Central composite design-response surface methodology (CCD-RSM) with three-factor (two numeric and one categorical) at three-level was used to select the appropriate solid substrate and to develop optimized SDNPs. The solid characterization by scanning electron microscopy, differential scanning calorimetry and powder X-ray diffraction studies indicated the absence of crystalline NFM in the formulations. The drug distribution analysis using raman spectroscopy suggested uniform distribution of amorphous NFM in optimized SDNPs-1 formulation. The transmission electron microscopy revealed the spherical structure of reconstituted SDNPs that releases amorphous NFM with globules size less than 110 nm. The solid substrate had significant and positive effect in drug dissolution; the mean dissolution time of NFM loaded in SDNPs was considerably improved. The bioavailability study resulted in enhanced magnitude of C_max and AUC for SDNPs. The tissue distribution studies exhibited significantly higher brain and lymph nodes distribution as compared to putative form. Overall, the results pointed towards the overwhelming response of the SDNPs to be used for HIV treatment.