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采用胡萝卜作为药物载体的固体分散体提高安贝生坦的溶解度和生物利用度:制剂、表征、体外和体内研究。

Enhancement of solubility and bioavailability of ambrisentan by solid dispersion using Daucus carota as a drug carrier: formulation, characterization, in vitro, and in vivo study.

机构信息

a Department of Pharmaceutics , Anuradha College of Pharmacy , Chikhli , India.

b Department of Pharmaceutics , Yash Institute of Pharmacy , Aurangabad , India.

出版信息

Drug Dev Ind Pharm. 2018 Jun;44(6):1001-1011. doi: 10.1080/03639045.2018.1428339. Epub 2018 Feb 5.


DOI:10.1080/03639045.2018.1428339
PMID:29382236
Abstract

Ambrisentan is an US FDA approved drug, it is the second oral endothelin A receptor antagonist known for the treatment of pulmonary arterial hypertension, but its oral administration is limited due to its poor water solubility. Hence, the objective of the investigation was focused on enhancement of solubility and bioavailability of ambrisentan by solid dispersion technique using natural Daucus carota extract as drug carrier. Drug carrier was evaluated for solubility, swelling index, viscosity, angle of repose, hydration capacity, and acute toxicity test (LD). Ambrisentan was studied for the saturation solubility, phase solubility, and Gibbs free energy change. Compatibility of drug and the natural carrier was confirmed by DSC, FTIR, and XRD. Solid dispersions were evaluated for drug content, solubility, morphology, in vitro, and in vivo study. Screening of the natural carrier showed the desirable properties like water solubility, less swelling index, less viscosity, and acute toxicity study revealed no any clinical symptoms of toxicity. Drug and carrier interaction study confirmed the compatibility to consider its use in the formulation. Formed particles were found to be spherical with smooth surface. In vitro studies revealed higher drug release from the solid dispersion than that of the physical mixture. Bioavailability study confirms the increased absorption and bioavailability by oral administration of solid dispersion. Hence, it can be concluded that the natural Daucus carota extract can be the better alternative source for the preparation of solid dispersion and/or other dosage forms for improving solubility and bioavailability.

摘要

安贝生坦是一种获得美国食品和药物管理局批准的药物,它是第二种用于治疗肺动脉高压的口服内皮素 A 受体拮抗剂,但由于其水溶性差,其口服给药受到限制。因此,本研究的目的是集中于通过使用天然胡萝卜提取物作为药物载体的固体分散技术来提高安贝生坦的溶解度和生物利用度。对药物载体的溶解度、溶胀指数、粘度、休止角、水化能力和急性毒性试验(LD)进行了评估。对安贝生坦进行了饱和溶解度、相溶解度和吉布斯自由能变化的研究。通过 DSC、FTIR 和 XRD 确认了药物与天然载体的相容性。对固体分散体进行了药物含量、溶解度、形态、体外和体内研究的评价。天然载体的筛选显示出理想的性质,如水溶性、较小的溶胀指数、较小的粘度和急性毒性研究没有显示出任何毒性的临床症状。药物和载体相互作用研究证实了其相容性,可考虑将其用于制剂。形成的颗粒呈球形,表面光滑。体外研究表明,固体分散体的药物释放速度高于物理混合物。生物利用度研究证实,通过口服固体分散体可提高吸收和生物利用度。因此,可以得出结论,天然胡萝卜提取物可以作为制备固体分散体和/或其他剂型以提高溶解度和生物利用度的更好替代来源。

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