FORMULATION, IN VITRO AND IN VIVO EVALUATION OF PALBOCICLIB SOLID DISPERSIONS

Abstract

Objective: The current research is aimed to enhance the dissolution and bioavailability of Palbociclib by formulating into solid dispersion Methods: The Palbociclib solid dispersions (SD) prepared by adopting different methods: Surface solid dispersion technique (SSD1-SSD15), Melt granulation (MG1-MG15) and Liquisolid compacts (LSC1-LSC9). All formulations were evaluated for physico-chemical parameters followed by in vitro dissolution studies. The optimised formulation was subjected to bioavailability studies in rats. Results: The results indicated that the prepared formulation satisfactory results for all the evaluated parameters. The SD formulations prepared by liquisolid compact and Melt Granulation technique (LSC1 and MG 3) displayed maximum dissolution of 99.64% and 99.58%. The FTIR of LSC1 displayed no interaction among drug and excipients while XRD, SEM displayed amorphous nature of drug in formulation. The stability study results indicated that LSC 1 was stable over 3 mo. The in vivo bioavailability studies conducted on rats indicate that at any time point, the drug plasma concentrations in animals administrated with the SD formulation was higher than pure drug. The Cmax of the palbociclib SD was 970.76±1.22 ng/ml and was significant (p<0.05) when compared to pure drug suspension formulation (105.84±0.19 ng/ml). The Tmax of both SD formulation and pure drug were 2.0±0.04 and 4±0.01 h, respectively. The AUC0-∞ for SD was higher 7816.61±1.37 ng. h/ml) than the pure drug suspension 2501.4±1.46 ng. h/ml indicating better systemic drug absorption from SD formulation prepared using Melt granulation technique. Conclusion: A significant enhancement in vitro dissolution profile and bioavailability of the melt granules was observed compared to the pure Palbocicilib and marketed product.