Chawla Garima, Bansal Arvind K
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research, Sector 67, Phase X, S.A.S. Nagar Punjab-160062, India.
Acta Pharm. 2008 Sep;58(3):257-74. doi: 10.2478/v10007-008-0016-1.
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 microg mL-1) was observed for tartaric acid (138 microg mL-1) and PVP (103 microg 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.
厄贝沙坦（IBS）是一种疏水性药物，其水溶性和溶解速率较差。分别用小分子（酒石酸和甘露醇）和聚合物添加剂（聚乙烯吡咯烷酮，PVP，以及羟丙基甲基纤维素，HPMC）制备了IBS的固体分散体。酒石酸（138μg mL-1）和PVP（103μg mL-1）的溶解度分别比结晶形式（14.6μg mL-1）提高了9.5倍和7倍。粉末X射线衍射证实，即使在含有低玻璃化转变温度赋形剂的情况下，IBS在所有情况下均以玻璃态存在。采用热分析方法（差示扫描量热法和热台显微镜）评估药物与添加剂的混溶性。这些技术表明，与其他三种情况下的“无定形悬浮液”相比，酒石酸导致生成“无定形溶液”。IBS的体外溶出取决于添加剂负载量，对于酸化赋形剂酒石酸而言，其溶出随浓度增加而增加。结果表明，即使是小分子也适合用于提高溶解度，这可归因于IBS良好的玻璃形成能力和保持玻璃态的合理能力。
