Acta Pharm. 58 (2008) 257-274
Original research paper
Improved dissolution of a poorly water soluble
drug in solid dispersions with polymeric and non-polymeric hydrophilic
additives
GARIMA CHAWLA and ARVIND K.
BANSAL
akbansal@niper.ac.in
Department of Pharmaceutical Technology
(Formulations), National Institute of Pharmaceutical Education and Research
(NIPER), Sector 67, Phase X, S.A.S. Nagar,
Punjab-160062, India
Accepted June 26, 2008
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 mg mL-1) was
observed for tartaric acid (138 mg mL-1) and PVP (103 mg 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