Al-Joufi Fakhria, Elmowafy Mohammed, Alruwaili Nabil K, Alharbi Khalid S, Shalaby Khaled, Alsharari Shakir D, Ali Hazim M
Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka P.O. Box 2014, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka P.O. Box 2014, Saudi Arabia.
Pharmaceutics. 2021 Mar 5;13(3):336. doi: 10.3390/pharmaceutics13030336.
Although it is a front-line in tuberculosis treatment, rifampicin (RF) exhibits poor oral bioavailability and hepatotoxicity. Rectal mucoadhesive and in situ rectal gels were developed to overcome drug drawbacks. A RF/polyethylene glycol 6000 co-precipitate was first prepared in different ratios. Based on the drug solubility, the selected ratio was investigated for drug/polymer interaction and then incorporated into in situ rectal gels using Pluronic F127 (15%) and Pluronic F68 (10%) as a gel base and mucoadhesive polymers (HPMC, sodium alginate and chitosan). The formulations were assessed for gelation temperature and gel strength. The selected formulation was investigated for in vivo assessments. The results showed that a 1:1 drug/polymer ratio exhibited satisfying solubility with the recorded drug/polymer interaction. Depending on their concentrations, adding mucoadhesive polymers shifted the gelation temperature to lower temperatures and improved the gel strength. The selected formulation (F4) did not exhibit any anal leakage or marked rectal irritation. Using a validated chromatographic analytical method, F4 exhibited higher drug absorption with a 3.38-fold and 1.74-fold higher bioavailability when compared to oral drug suspension and solid suppositories, respectively. Toxicity studies showed unnoticeable hepatic injury in terms of biochemical, histopathological and immunohistochemical examinations. Together, F4 showed a potential of enhanced performance and also offered lower hepatic toxicity, thus offering an encouraging therapeutic alternative.
尽管利福平（RF）是结核病治疗的一线药物，但其口服生物利用度较差且具有肝毒性。为克服这些药物缺点，研发了直肠黏膜黏附原位凝胶。首先以不同比例制备了利福平/聚乙二醇6000共沉淀物。根据药物溶解度，研究了所选比例的药物/聚合物相互作用，然后使用普朗尼克F127（15%）和普朗尼克F68（10%）作为凝胶基质和黏膜黏附聚合物（羟丙基甲基纤维素、海藻酸钠和壳聚糖）将其掺入原位直肠凝胶中。对制剂的凝胶化温度和凝胶强度进行了评估。对所选制剂进行了体内评估。结果表明，药物/聚合物比例为1:1时具有令人满意的溶解度，并记录了药物/聚合物相互作用。根据其浓度，添加黏膜黏附聚合物可将凝胶化温度降低，并提高凝胶强度。所选制剂（F4）未出现任何肛门渗漏或明显的直肠刺激。使用经过验证的色谱分析方法，与口服药物混悬液和固体栓剂相比，F4的药物吸收更高，生物利用度分别高3.38倍和1.74倍。毒性研究表明，在生化、组织病理学和免疫组织化学检查方面，肝损伤不明显。总之，F4显示出增强性能的潜力，并且肝毒性较低，因此提供了一种令人鼓舞的治疗选择。
