Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.
School of Pharmacy and Traditional Chinese Pharmacy, Jiangsu College of Nursing, Huaian, China.
Drug Deliv. 2020 Dec;27(1):712-722. doi: 10.1080/10717544.2020.1760402.
For weakly basic drugs, the sharp decrease of drug solubility and the following drug precipitation after drugs transferring from the gastric fluid to the intestinal fluid in the gastrointestinal (GI) tract is a main reason for the poor oral bioavailability of drugs. Here, an anticoagulant dabigatran etexilate (DE) was used as a model drug, and a composite nanocarrier system of DE was developed to improve the drug dissolution by decreasing the drug leakage in the stomach and inhibiting the drug precipitation in the intestinal tract. With the encapsulation of drugs in nanocarriers, the precipitation percentage of DE in composite nanocarriers was 22.25 ± 3.88% in simulated intestinal fluid, which was far below that of the commercial formulation. Moreover, the relative bioavailability of DE-loaded composite nanocarriers (456.58%) was greatly enhanced and the peak of its activated partial thromboplastin time was also significantly prolonged ( .01) compared with the commercial formulation, indicating that the anticoagulant effect of DE was effectively improved. Therefore, the designed composite nanocarrier system of DE presents great potentials in improving the therapeutic efficiency and expanding the clinical applications of poorly water-soluble weakly basic drugs.
对于弱碱性药物来说，药物从胃液转移到胃肠道中的肠液后溶解度急剧下降，随后药物沉淀，这是药物口服生物利用度差的主要原因。在这里，我们选择抗凝药达比加群酯（DE）作为模型药物，开发了一种复合纳米载体系统，通过减少药物在胃中的泄漏和抑制药物在肠道中的沉淀来提高药物的溶解率。通过将药物包封在纳米载体中，在模拟肠液中，复合纳米载体中 DE 的沉淀百分比为 22.25 ± 3.88%，远低于商业制剂。此外，与商业制剂相比，载有 DE 的复合纳米载体的相对生物利用度（456.58%）大大提高，其活化部分凝血活酶时间的峰值也显著延长（p < 0.01），表明 DE 的抗凝效果得到了有效改善。因此，设计的 DE 复合纳米载体系统在提高治疗效率和扩大弱碱性难溶性药物的临床应用方面具有很大的潜力。
