Volume 4

October-December 2012

Solid dispersion as an approach for dissolution enhancement and delivery of trandolapril, a poorly water-soluble ace inhibitor

Ofokansi K C, Kenechukwu F C, Isah A B, Ogbonna J D N

Abstract: 
This study was designed to formulate and evaluate solid dispersions as novel carrier system for the delivery of trandolapril. Trandolapril-loaded solid dispersions (SDs) were prepared by fusion method using varying combination ratios of Eudragit RL 100 and polyethylene glycol (PEG) 8000 with or without urea as a hydrophilic carrier. Characterization based on surface morphology, particle size, absolute drug content and moisture sorption properties were carried out on the SDs. The in vitro release of trandolapril from the SDs was performed in 0.1 N HCl (pH 1.2) and phosphate buffered saline (PBS, pH 7.4). To evaluate the mechanism of release of trandolapril from the SDs, the in vitro release data from different batches of the SDs were fitted into different kinetic models. Results indicate that discrete and irregular SDs of mean particle size range 3.87 ± 0.15 to 22.14 ± 1.09 µm, which were stable over 3 months, were obtained. SDs containing urea entrapped greater amounts of drug in comparison with SDs containing only Eudragit RL 100 and PEG 8000. The moisture sorption studies indicate that both amorphous and microcrystalline state of trandolapril are present in the SDs. In vitro release studies revealed that there was marked increase in the dissolution rate of trandolapril from the solid dispersions when compared to pure trandolapril. The improved dissolution, which was better in PBS than in 0.1 N HCl, was highest in the SDs containing Eudragit RL 100, PEG 8000 and urea. The increased dissolution rate of trandolapril may be due to the formation of microcrystals, increased wettability and dispersibility in systems containing Eudragit RL 100, PEG 8000 and urea. The release pattern of the drug was found to follow predominantly the Higuchi square root model. This study has shown that a formulation of trandolapril SDs could offer a better and more effective approach of increasing the dissolution rate of the poorly water-soluble prodrug, trandolapril.

Keywords: Trandolapril, Solid Dispersion, Urea, PEG 8000, Dissolution, Eudragit RL 100, Moisture Sorption.