Comparative Studies on Dissolution and Bioavailability of Tamoxifen Citrate Loaded Binary and Ternary Solid Dispersions

Abstract

Aims: This study focused on comparing binary and ternary solid dispersions (SD's) of water-insoluble Tamoxifen citrate (TMC) regarding drug dissolution and oral bioavailability. Basically, the enhanced dissolution of this drug by water-soluble polymer has not yet been reported in literature. Study Design: In vitro and In-vivo characterization of Tamoxifen citrate loaded binary and ternary solid dispersion systems. Place and Duration of Study: Department of Pharmaceutics and Industrial Pharmacy, Helwan University, Cairo, Egypt between June 2012 and June 2013. Methodology: Amorphous SD's of TMC with two hydrophilic polymers, polyethylene glycol 6000 (PEG 6000) and Methyl cellulose (MC), were prepared by melting method. Binary SD's of TMC with PEG of different weight ratios were prepared. MC was used as third component to prepare ternary SD's. Physicochemical properties of SD's were characterized by FTIR, DSC, and In-vitro drug release in comparison with physical mixtures and the drug alone. Oral bioavailability of the optimized SD formula was compared with that of free TMC in rats. Results: Infrared spectroscopic studies suggested no interaction between TMC and polymers rather than H-bond formation. A remarkably improved dissolution of drug from the ternary solid dispersion systems when compared to the binary solid dispersion systems was detected. On the basis of % dissolution efficiency (% DE), the SD composed of PEG: TMC: MC in a ratio 4:1:2 w/w/w was selected as the optimized SD. The in-vivo studies showed extremely significant higher values of Cmax (P<.05), AUC0-24 (P<.05) and significantly (P<.05) lower values of Tmax exhibited by SD compared with free TMC. Conclusion: Highly enhanced TMC dissolution and bioavailability exhibited by PEG: TMC: MC ternary solid dispersion in a weight ratio 4:1:2 were promising to improve the therapeutic potential of TMC.