Formulation Approaches for Dissolution Enhancement of Telmisartan

Abstract

Low aqueous solubility is the major problem confronted with formulation development. The challenge to achieve desired dissolution characteristics, stability and in vivo performance becomes more stringent with drugs which are highly hydrophobic (log P > 3) and having exceedingly pH dependent solubility characteristics. Telmisartan, an angiotensin II receptor antagonist (ARB) widely used in the management of hypertension is a representative example of this category. It is a BCS Class II drug which has extremely low solubility in water (0.09 μg/ml) as well as pH dependent solubility which can be observed in a pH range of 3 to 9. In the present study, two of the major techniques for solubility enhancement were investigated, one of which was Liquisolid compaction. Here, compacts were prepared using Avicel PH 102 as carrier material and Aerosil 200 as coating material with varying drug: vehicle ratio and carrier: coating ratio (excipient ratio) and it was observed that highest drug dissolution was obtained at 1:6 drug: vehicle ratio and 5:1 excipient ratio respectively. Another technique which was investigated was inclusion complexation. Inclusion complex was prepared by physical mixing, kneading and solvent evaporation method with varying drug: complexing agent ratio and it was observed that highest drug dissolution was observed in complexes prepared by kneading method. On comparing both the techniques it was concluded that each technique resulted in dissolution enhancement of Telmisartan. However, on comparison inclusion complexation resulted in higher solubility enhancement than liquisolid compaction whereas liquisolid compaction offered an added advantage of direct formulation as a dosage form.