难溶性药物阿替洛尔单层芯渗透泵片的制备

Preparation of Monolithic Osmotic Pump Tablet of Poorly Soluble Atenolol

目的以阿替洛尔为模型药物,通过酸碱反应提高难溶性药物的溶解能力并制备单层芯渗透泵片。方法在处方中加入酒石酸使其与阿替洛尔的碱性基团反应从而增强药物的溶解性,用自行设计的带针冲头压制带孔片芯,以乙基纤维素为膜材包衣制备渗透泵片,采用相似因子作为指标筛选处方。结果在酒石酸溶液中阿替洛尔的溶解能力大幅度提高,制备的阿替洛尔单层芯渗透泵片能在24h内匀速释放药物,且释药行为不受桨转速和释放介质的影响。结论用酒石酸提高阿替洛尔的溶解能力并进而制备单层芯渗透泵片的方法是可行的。酸碱反应增溶药物的方法可望推广到其他难溶于水,但具有酸碱反应能力药物的增溶和渗透泵片的制备。

OBJECTIVE To enhance the soluble ability of the poorly water-soluble drug by acid-alkali reaction and prepare monolithic osmotic pump tablet using atenolol as model drug. METHODS Tartaric acid was incorporated into the formulation to enhance the soluble ability of atenolol. The osmotic pump tablets were prepared by coating the indented core tablets. Similarity factor was used to evaluate the formulations of osmotic pump tablets. RESULTS The soluble ability of atenolol was enhanced markedly in tartaric acid aqueous solution. The prepared osmotic pump tablets were able to release atenolol at a zero-order manner up to 24 h. Agitation rate and release media showed no effect on atenolol release. CONCLUSION It was feasible to enhance the soluble ability and prepare the monolithic osmotic pump tablet of atcnolol with tartaric acid. The approach of solubility-modulated by acid-alkali reaction might be used for solubilization and the preparation of osmotic pump tablet of other poorly water-soluble drugs with ability to react with an acid or an alkali.