Original scientific paper

https://doi.org/10.2478/v10007-008-0016-1

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

GARIMA CHAWLA ; Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, Phase X, S.A.S. Nagar, Punjab-160062, India
ARVIND K. BANSAL ; Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, Phase X, S.A.S. Nagar, Punjab-160062, India

Abstract

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 (polyvinylpyrrolidone, PVP, and hydroxy propyl methylcellulose, HPMC). A 9.5 and 7 folds enhancement in solubility over the crystalline form (14.6 g mL-1) was observed for tartaric acid (138 g mL-1) and PVP (103 g 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.

Keywords

irbesartan; solid dispersion; amorphous form; solubility; dissolution rate

Hrčak ID:

25021

URI

https://hrcak.srce.hr/25021

Publication date:

1.9.2008.

Article data in other languages: croatian

Visits: 4.419 *