Enhancement of dissolution of ethopropazine using solid dispersions prepared with phospholipid and/or polyethylene glycol

The purpose of this study was to improve the dissolution properties of a po orly water soluble and bioavailable drug, ethopropazine HCl (ET), by incorp orating the drug in three different types of solid dispersion systems. Soli d dispersion of ET were prepared using 1:1 (w/w) ratios of (1) phospholipid (1,2 dimyristoyl-sn-glycerophosphocholine) (DMPC), (2) polyethylene glycol 8000 (PEG8000), and (3) a novel combination of both DMPC and PEG8000. Usin g the solvent method of preparation Et and DMPC and/or PEG were dissolved i n chloroform, and solvent subsequently was evaporated using nitrogen gas. T he resulting solid dispersion(s) was passed through a 60-mesh sieve. Charac terization of ET/DMPC solid dispersion was performed by differential scanni ng calorimetry (DSC) and X-ray diffractometry studies. Dissolution studies conducted in phosphate buffered saline (PBS) (pH 7.4, 37 degreesC +/- 0.5 d egreesC) using the USP type II (paddle) dissolution apparatus showed signif icant increases int eh dissolution rate of ET with all the solid dispersion s in this study. Specifically, within the first 5 min (D5), solid dispersio ns containing ET/DMPC (1:1) showed an eightfold increase in dissolution; in combination with DMPC and PEG8000 (1:1), there was an approximately sixfol d increase; and a fourfold increase was observed with PEG8000 (1:1). Comple te dissolution of all solid dispersions occurred within 60 min (D60) of the run. Storage of the ET/DMPC sample for over 4.5 months revealed a decrease in the dissolution rate when compared to freshly prepared sample. Overall, it was concluded that the dissolution rate of ET significantly improved wh en dispersed in all the selected carrier systems. However, the solid disper sion of ET/DMPC was observed to be superior to the other combinations used.