Improved dissolution of a poorly water soluble drug in solid dispersions with polymeric and non-polymeric hydrophilic additives.

摘要

Irbesartan (IBS) is a hydrophobic drug with poor aqueous solubility and dissolution rate. Solid dispersions (SDs) of IBS were prepared with both small molecules (tartaric acid and mannitol) and polymeric additives (polyvinyl-pyrrolidone, PVP, and hydroxypropyl methylcellulose, HPMC). A 9.5 and 7 folds enhancement in solubility over the crystalline form (14.6 mug mL-1) was observed for tartaric acid (138 mug mL-1) and PVP (103 mug mL-1), respectively. Powder X-ray diffraction confirmed that IBS existed in the glassy state in all cases, even with excipients having low glass transition temperature. Thermal methods (differential scanning calorimetry and hot stage microscopy) were used to evaluate the miscibility of the drug and additives. These techniques suggested that tartaric acid led to generation of >amorphous solutions< in contrast to >amorphous suspensions< in other three cases. The in vitro dissolution of IBS depended on the additive load and increased with increasing concentration in the case of tartaric acid, an acidifying excipient. The results indicate the suitability of even small molecules for providing solubility benefits, which can be attributed to the good glass forming ability and reasonable ability of IBS to remain in the glassy state.