BIOAVAILABILITY ENHANCEMENT OF POORLY SOLUBLE RALOXIFENE BY DESIGNING INCLUSION COMPLEX WITH β–CYCLODEXTRIN

摘要

Objective: Raloxifene hydrochloride (RLX) is widely used in the treatment of osteoporosis, but due to its extensive first pass metabolism bioavailability of RLX is remaining only 2%. In addition of that being from BCS class II, RLX has poor water solubility. Therefore the objective of present research work was to enhance solubility and dissolution rate of RLX by formulating inclusion complex with β cyclodextrin (β-CD) as a carrier. Methods: Inclusion complex was prepared by various methods like physical mixture, co-precipitation method and kneading method using different drug to carrier ratios (1:1, 1:2 and 1:3). Results: Inclusion complex prepared with co-precipitation method had shown 5.5 fold improvements in water solubility and significant increment in dissolution rate when compared with plain RLX. Optimized formulation was characterized by Fourier transform infrared spectroscopy, Differential scanning calorimetry, X-ray diffraction and Scanning electron microscopy studies for their compatibility, thermal analysis, crystallinity and surface morphology determination, respectively. Results of DSC and XRD study suggested the conversion of RLX from crystalline form to amorphous form. Stability studies showed stable formulation up to the period of 6 months. In vivo pharmacokinetic study was also conducted in wistar rats for optimized drug loaded inclusion complex that showed nearby two fold increments in drug bioavailability compared to plain drug suspension. Conclusion: From these studies, it can be concluded that solubility and dissolution rate of poorly soluble raloxifene could be remarkably increased by formulating into the inclusion complex with β-CD which results in significant improvement in bioavailability of poorly soluble RLX. Keywords: Bioavailability, Dissolution rate, BCS classification, Inclusion complex, Carrier.