El-Say Khalid M, Ahmed Tarek A, Ahmed Osama A A, Hosny Khaled M, Abd-Allah Fathy I
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
J Pharm Sci. 2017 Sep;106(9):2447-2456. doi: 10.1016/j.xphs.2017.01.001. Epub 2017 Jan 10.
Owing to limited solubility, vitamin K undergoes low bioavailability with large inter-individual variability after oral administration. This article aimed to prepare self-nanoemulsifying lyophilized tablets (SNELTs) for the flash oral transmucosal delivery of vitamin K. Twenty-one formulae of vitamin K self-nanoemulsifying drug delivery systems (SNEDDS) were prepared using different concentrations of vitamin K, Labrasol, and Transcutol according to mixture design. The SNEDDS was loaded on porous carriers and formulated as lyophilized tablets. The release profile and the pharmacokinetic parameters of vitamin K SNELTs were evaluated in comparison with commercial tablets and ampoules on human volunteers. Results revealed that the optimized SNEDDS showed the smallest and most stable nanoemulsion globules. SNELTs were prepared successfully and showed substantial superiority drug release compared with the commercial tablets. Interestingly, SNELTs enhanced both rate and extent of vitamin K absorption as well as relative bioavailability (169.67%) in healthy subjects compared with the commercial tablets. SNELTs revealed promising no significant difference in the area under the curve compared with the commercial intramuscular injection. SNELTs enhanced dissolution and bioavailability that expected to have the strong impact on the efficiency of vitamin K in the prophylaxis and treatment of bleeding disorders in patients with hepatic dysfunction.
由于溶解度有限，维生素K口服给药后生物利用度较低，个体间差异较大。本文旨在制备用于维生素K速释口腔黏膜给药的自纳米乳化冻干片（SNELTs）。根据混合设计，使用不同浓度的维生素K、Labrasol和Transcutol制备了21种维生素K自纳米乳化药物递送系统（SNEDDS）配方。将SNEDDS负载于多孔载体上并制成冻干片。在人体志愿者中，与市售片剂和安瓿剂相比，评估了维生素K SNELTs的释放曲线和药代动力学参数。结果显示，优化后的SNEDDS显示出最小且最稳定的纳米乳液球。成功制备了SNELTs，与市售片剂相比，其药物释放具有显著优势。有趣的是，与市售片剂相比，SNELTs提高了健康受试者中维生素K的吸收速率和程度以及相对生物利用度（169.67%）。与市售肌肉注射剂相比，SNELTs在曲线下面积方面显示出无显著差异。SNELTs提高了溶出度和生物利用度，预计对维生素K预防和治疗肝功能不全患者出血性疾病的疗效有重大影响。
