The objective of the present study was to evaluate the potential of solid dispersion adsorbate to improve the solubility and bioavailability of rivaroxaban (RXN). Solid dispersion adsorbate (SDA) of RXN was developed by fusion method using PEG 4000 as carrier and Neusilin as adsorbent. A 32 full factorial design was utilized to formulate various SDAs. The selected independent variables were amount of carrier (X1) and amount of adsorbate (X2). The responses measured were time required for 85% drug release (Y1) and saturated solubility (Y2). MTT assay was employed for cytotoxicity studies on Caco-2 cells. In vivo pharmacokinetics and pharmacodynamic evaluations were carried out to assess the prepared SDA. Pre-compression evaluation of SDA suggests the prepared batches (B1-B9) possess adequate flow properties and could be used for compression of tablets. Differential scanning calorimetry and X-ray diffraction data signified the conversion of crystalline form of drug to amorphous form, a key parameter accountable for improvement in drug dissolution. Optimization data suggests that the amount of carrier and amount of adsorbate significantly (P < 0.05) influence both dependent variables (time required for 85% drug release and saturated solubility). Post-compression data signifies that the compressibility behavior of prepared tablets were within the official standard limits. Significant increase (P < 0.0001) in the in vitro dissolution characteristics of RXN was noticed in optimized SDA (>85% in 10 min) as compared to pure drug, marketed product and directly compressible tablet. Cytotoxicity studies confirm nontoxicity of prepared RXN SDA tablets. Higher Cmax and AUC achieved with RXN SDA tablets indicated enhancement in oral bioavailability (~3 folds higher than the RXN suspension). Higher bleeding time and percentage of platelet aggregation noticed with RXN SDA tablets further substantiate the efficacy of the prepared formulation. In summary, the results showed the potential of RXN SDA tablets to enhance the bioavailability of RXN and hence can be an alternate approach of solid dosage form for its development for commercial application.
The aim of the present study was to formulate saquinavir mesylate loaded nanostructured lipid carriers (SQVM-NLC) and evaluate its brain distribution after nasal administration. NLCs reveal some advantages for drug therapy over conventional carriers, including increased solubility, the ability to enhance storage stability, improved permeability and bioavailability, reduced adverse effect, prolonged half-life, and tissue-targeted delivery. SQVM-NLCs were prepared by hot high pressure homogenization and subsequent stabilization by lyophilization. QVM- NLC developed showed a particle with the size of 124.4 nm, polydispersity index of 0.267, entrapment efficiency of 73% and the zeta potential of -24.9 mV. The results from Scanning Electron Microscopy (SEM), powder X-ray diffraction (XRD)and differential scanning calorimetry (DSC) demonstrated that SQVM was present in NLC in an encapsulated molecule form. Mucosal toxicity study on sheep nasal mucosa showed no significant adverse effect of SQVMloaded NLC. SQVM-NLC showed slower release compared with saquinavir mesylate suspension in vitro. In vivo brain distribution studies demonstrated desired drug concentration in brain after intra nasal administration of SQVM-NLC than PDS. The results of the study also suggest that SQVM-NLC could be a promising drug delivery system for antiretroviral therapy.
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