Improving the Dissolution and Bioavailability of Nifedipine Using Solid Dispersions and Solubilizers

Abstract

ABSTRACTNifedipine (NF) is a poorly water-soluble drug, of low and irregular bioavailability after oral administration. Although some reports have attempted to improve the dissolution of NF using solid dispersions and solubilizers, little literature information is available on the in vivo performance of such preparations. The aim of the present work was to improve the therapeutic efficacy of NF via incorporation into different types of carriers, and to investigate their in vitro dissolution and bioavailability in rabbits. Nifedipine solid dispersions were prepared by fusion, solvent, and freeze-drying methods with polyethylene glycol (PEG) 6000 and PEG monomethylether 5000 (PEG MME 5000). Complexation of NF with β-cyclodextrin (β-CyD) and solubilization by sodium lauryl sulfate (SLS) have also been studied. The dissolution was determined by the flow-through cell in order to maintain perfect sink conditions. The solid dispersions resulted in a significant increase in the dissolution rate as compared to pure drug. The highest NF dissolution rate was obtained from solid dispersions containing 95% PEG 6000 prepared by the solvent method. While, unexpectedly, the highest absorption in rabbits was obtained from 95% PEG 6000 prepared by the fusion method. Compared to SLS, β-CyD gave higher in vitro and in vivo values. Differential scanning calorimetry (DSC) and powder x-ray diffractometry indicated that NF in solid dispersions is homogeneously distributed, and no drug crystallized out of the system. The DSC thermograms of NF-β-CyD complex and NF/SLS solid mixture showed a decrease in the NF endothermic peak. The x-rays showed different diffraction patterns of pure NF and pure carrier, suggesting the formation of a new solid form.