以尿素为载体,采用不同固体分散技术提高奥美沙坦的溶出度

B. Sangameswaran, M. Gomathi
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引用次数: 0

摘要

药物在水中的溶解度差,在胃肠道水溶液中的溶出率低,往往导致生物利用度不足。根据生物制药分类系统(BCS),奥美沙坦属于ii类,溶解度差,渗透性高。由于只有溶解的药物才能通过胃肠道膜,因此最终需要药物的适当溶解度。口服生物利用度为26%。为此,采用熔融、捏合、共沉淀法、溶剂蒸发、物理混合等不同工艺配制固体分散体,以提高其溶解度,并采用1:1、1:2、1:3、1:4等不同比例的药物与载体(尿素)配制固体分散体。FTIR研究了药物与载体的相容性,结果表明药物与载体之间没有相互作用。休止角、容重、攻丝密度;计算了所有固体分散体的卡尔指数和豪斯纳比。在所有配方中发现药物含量高且均匀。与其他配方相比,制备的固体分散体SEM4(1:4)的润湿时间最短为13秒。在pH为6.8的磷酸盐缓冲液中进行体外溶出度、释放度研究表明,制备的固体分散体与纯药物相比,药物释放速度更快。体外溶出度随载体浓度的增加呈上升趋势
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Enhancement of dissolution rate of Olmesartan medoxomil using urea as carrier by different solid dispersion techniques
The poor solubility of drug substances in water and their low dissolution rate in aqueous G.I.T fluid often leads to insufficient bioavailability. As per Biopharmaceutical Classification System (BCS), Olmesartan belongs to the class-II category having poor solubility and high permeability. Since only dissolved drug can pass the gastrointestinal membrane, the proper solubility of the drug is ultimately desired. Its oral bioavailability is 26%. Hence, an attempt was made to enhance its solubility by formulating solid dispersions using different techniques viz., Melting, Kneading, Co-precipitation, Solvent evaporation and Physical mixing etc., Drug and carrier (Urea) in different ratios like 1: 1, 1: 2, 1: 3 and 1:4 were used for formulating solid dispersions. The compatibility of the drug with the carrier was checked by FTIR studies, these results revealed that there was no interaction between them. The angle of repose, bulk density, tapped density; Carr’s index and Hausner ratio were calculated for the micrometric characterization of all the solid dispersions. The drug content was found to be high and uniform in all formulations. The prepared Solid dispersion SEM4 (1:4) showed minimal wetting time of 13 seconds compared with the other formulations. In vitro dissolution, release studies in Phosphate buffer pH of 6.8 revealed that the prepared solid dispersions showed faster drug release compared with the pure drug.  The in vitro dissolution profile showed ascendency on increasing the carrier concentration
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