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 poorly water soluble and bioavailable drug, ethopropazine HCl (ET), by incorporating the drug in three different types of solid dispersion systems. Solid dispersions 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. Using the solvent method of preparation, ET and DMPC and/or PEG were dissolved in chloroform, and solvent subsequently was evaporated using nitrogen gas. The resulting solid dispersion(s) was passed through a 60-mesh sieve. Characterization of ET/DMPC solid dispersion was performed by differential scanning calorimetry (DSC) and X-ray diffractometry studies. Dissolution studies conducted in phosphate buffered saline (PBS) (pH 7.4, 37 degrees C +/- 0.5 degrees C) using the USP type II (paddle) dissolution apparatus showed significant increases in the dissolution rate of ET with all the solid dispersions in this study. Specifically, within the first 5 min (D5), solid dispersions containing ET/DMPC (1:1) showed an eightfold increase in dissolution; in combination with DMPC and PEG8000 (1:1), there was an approximately sixfold increase; and a fourfold increase was observed with PEG8000 (1:1). Complete 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 when dispersed in all the selected carrier systems. However, the solid dispersion of ET/DMPC was observed to be superior to the other combinations used.
Prabhu
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S
College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA. sprabhu@westernu.edu
Brocks
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Betageri
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D002152:Calorimetry, Differential Scanning; D018680:Cholinergic Antagonists / Q000737:chemistry*; D004134:Dimyristoylphosphatidylcholine / Q000031:analogs & derivatives* / Q000737:chemistry*; D015195:Drug Design; D004355:Drug Stability; D010640:Phenothiazines / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
C108836:1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine; D018680:Cholinergic Antagonists; D010640:Phenothiazines; D010743:Phospholipids; D011092:Polyethylene Glycols; C084820:profenamine; D004134:Dimyristoylphosphatidylcholine