Department of Oral Diagnostic Sciences, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Drug Deliv. 2022 Dec;29(1):2773-2783. doi: 10.1080/10717544.2022.2115165.
Based on the administration convenience, transmucosal buccal drug delivery allows special strength points over peroral routes for systemic delivery. It could achieve local or systemic effect and boost drugs' bioavailability for agents with first pass metabolism. The current study aimed to manufacture and optimize a lavender oil-based nanoemulsion loaded with zaleplon and incorporate it into fast-disintegrating tablets to promote its dissolution and oral bioavailability via oral mucosa. Zaleplon-loaded nanoemulsions were devised with various levels of lavender oil (10% to 25%), the surfactant Sorbeth-20 (35% to 65%), and the co-surfactant HCO-60 (20% to 40%); the extreme vertices mixture statistical design was adopted. The droplet size and drug-loading efficiency were the evaluated. The optimal formulation was transformed into self-nanoemulsified lyophilized tablets (ZP-LV-SNELTs), which were tested for their uniformity of content, friability, and disintegration time with in-vitro release. Finally, the pharmacokinetic parameters of the ZP-LV-SNELTs were determined and compared with those of marketed formulations. The optimal nanoemulsion had a droplet size of 87 nm and drug-loading capacity of 185 mg/mL. ZP-LV-SNELTs exhibited acceptable friability and weight uniformity and a short disintegration time. The in-vitro release of ZP-LV-SNELTs was 17 times faster than that of the marketed tablet. Moreover, the optimal ZP-LV-SNELTs increased the bioavailability of zaleplon in rabbits by 1.6-fold compared with the commercial tablets. Hence, this investigation revealed that ZP-LV-SNELTs delivered zaleplon with enhanced solubility, a fast release, and boosted bioavailability thru oral mucosa which provided a favorable route for drug administration which is suggested to be clinically investigated in future studies.
基于管理便利性,经口腔黏膜给药比口服途径更有利于全身给药。它可以实现局部或全身作用,并提高具有首过代谢的药物的生物利用度。本研究旨在制造和优化一种载有扎来普隆的薰衣草油基纳米乳,并将其纳入速崩片,通过口腔黏膜促进其溶解和口服生物利用度。载有扎来普隆的纳米乳采用不同水平的薰衣草油(10%至 25%)、表面活性剂 Sorbeth-20(35%至 65%)和助表面活性剂 HCO-60(20%至 40%)进行设计;采用极端顶点混合统计设计。评价了粒径和载药量。优化的配方转化为自微乳冻干片(ZP-LV-SNELTs),对其内容物均匀度、脆碎度和体外释放的崩解时间进行了测试。最后,测定了 ZP-LV-SNELTs 的药代动力学参数,并与市售制剂进行了比较。最佳纳米乳粒径为 87nm,载药量为 185mg/mL。ZP-LV-SNELTs 表现出可接受的脆碎度和重量均匀度以及较短的崩解时间。ZP-LV-SNELTs 的体外释放速度比市售片剂快 17 倍。此外,与市售片剂相比,最佳的 ZP-LV-SNELTs 使扎来普隆在兔子体内的生物利用度提高了 1.6 倍。因此,这项研究表明,ZP-LV-SNELTs 通过口腔黏膜给药提供了一种增强扎来普隆溶解度、快速释放和提高生物利用度的途径,为药物管理提供了一种有利途径,建议在未来的研究中进行临床研究。