Enhancement of dissolution rate and intestinal stability of candesartan cilexitil.

ABSTRACT

The objective of this work was to improve the dissolution rate of candesartan cilexitil, a poorly water soluble prodrug and to reduce its premature degradation in the intestinal lumen. Binary and ternary solid dispersions (SD) of the drug with Pluronic F68, Polyvinyl pyrrolidone (PVP), Hydroxypropyl Methylcellulose (HPMC) and Tween 80 were prepared using the solvent evaporation method. The dissolution rate of the drug was monitored and the prepared SD systems were characterized using thermal analysis and Fourier transform infrared (FTIR) spectroscopy. The stability of candesartan in extracted rabbit intestinal fluids was monitored. This was conducted in absence and presence of tested excipients. SD of the drug with PVP resulted in significant enhancement in the dissolution rate of drug even at the lowest drug to polymer weight ratio. Similarly, SD with HPMC showed enhanced dissolution rate. SD with Pluronic F68 showed promising dissolution enhancement but this was recorded at higher polymer concentrations. Formulation of ternary SD of the drug and PVP with either Pluronic or Tween 80 resulted in rapid drug dissolution. The enhanced dissolution was mainly due to amorphousization of the drug with possible contribution to the micelle formation as reflected from thermal analysis. Incubation of pure candesartan in intestinal fluid resulted in rapid degradation of the drug. This degradation was not affected by 0.1% Pluronic. In presence of Tween 80 the rate of drug degradation was reduced significantly with the efficacy of Tween 80 depending on its concentration. The study developed a system for enhanced dissolution rate of candesartan with better stability in the intestinal lumen.