Development and pharmacokinetic evaluation of nebilolol solid dispersion using novel polymers

Abstract

In the present investigation, fifteen Nebivolol solid dispersion formulations were prepared with 1:1:1, 1:5:2 and 1:3:1.5 ratios of drug: carrier: surfactant by solvent evaporation method. There was significant improvement in the rate of drug release from all 15 solid dispersions and the formulation (SD14) comprising Nebivolol: Kleptose HPB: SLS in 1:5:2 ratio has shown enhanced solubility about 42 folds and significant improvement in the rate of drug release i.e.  From powder X-ray diffraction (p-XRD) and by scanning electron microscopy (SEM) studies it was evident that polymorphic form of Nebivolol has been converted into an amorphous form from crystalline within the solid dispersion formulation. From in vivo bioavailability studies, Cmax  of the optimized formulation SD14 was 2.44±0.06ng /ml, was significantly higher as  compared to  pure drug suspension, i.e.,  1.58±0.02ng/ml. Tmax   of optimized formulation was decreased significantly when compared with pure drug (1.00±0.04hr, 2.00±0.03hr), AUC0-α  and  AUC0-t   for  optimized solid dispersion formulation was significantly higher (p<0.05) as compared to pure drug suspension. The present study demonstrated that formulation of Nebivolol solid dispersion by solvent evaporation technique is a highly effective strategy for enhancing the bioavailability of poorly water soluble Nebivolol.