Abstract:
The purpose of this study was to formulate and evaluate trandolapril/poloxamer 188 solid dispersions (SDs) for improved delivery of trandolapril, a poorly water-soluble antihypertensive prodrug. Poloxamer 188 was employed as a hydrophilic carrier at various trandolapril: poloxamer 188 ratios to prepare trandolapril-loaded SDs by fusion method. Characterization based on surface morphology, particle size, entrapment efficiency and moisture sorption properties were carried out on the SDs. Compatibility study was carried out using Fourier transform infrared (FT-IR) spectroscopy while the in vitro dissolution of trandolapril from the SDs was performed in phosphate buffered saline (PBS, pH 7.4). The results showed that discrete and irregularly-shaped SDs of average particle size in the range 2.16 ± 0.78 to 2.94 ± 0.25 µm, which were stable over 3 months, were obtained. The moisture sorption studies indicated the amorphous/ microcrystalline state of trandolapril in the SDs, which also exhibited good entrapment efficiency (EE%) and marked increase in the dissolution rate of trandolapril from the SDs when compared to pure trandolapril (unformulated trandolapril). Spectroscopic studies indicate that there was no strong chemical interaction between the drug and poloxamer 188 which, when incorporated inside SD, had prominent effect in improvement of trandolapril dissolution. As we increased poloxamer 188 concentration in SD formulation, the dissolution rate of the drug (trandolapril) increased, which may be due to the formation of microcrystals, increased wettability and dispersibility in the formulations. The present finding has shown that trandolapril/poloxamer 188 SDs is a potential carrier system for dissolution and bioavailability enhancement of the poorly water-soluble anti-hypertensive prodrug, trandolapril.

Keywords: Solid Dispersions (SDs), Drug Dissolution, Trandolapril, Moisture Sorption, Poloxamer 188.