Department of Pharmacy, University of Malakand, Chakdara Dir (Lower), Khyber Pakhtunkhwa, Chakdara, 18800, Pakistan.
AAPS PharmSciTech. 2024 Jul 9;25(6):157. doi: 10.1208/s12249-024-02861-3.
Azithromycin traditional formulations possesses poor oral bioavailability which necessitates development of new formulation with enhanced bioavailability of the drug. The objective of current research was to explore the kinetics and safety profile of the newly developed azithromycin lipid-based nanoformulation (AZM-NF). In the in-vitro study of kinetics profiling, azithromycin (AZM) release was assessed using dialysis membrane enclosing equal quantity of either AZM-NF, oral suspension of azithromycin commercial product (AZM-CP), or azithromycin pure drug (AZM-PD) in simulated intestinal fluid. The ex-vivo study was performed using rabbit intestinal segments in physiological salts solution in a tissue bath. The in-vivo study was investigated by oral administration of AZM to rabbits while taking blood samples at predetermined time-intervals, followed by HPLC analysis. The toxicity study was conducted in rats to observe histopathological changes in rat's internal organs. In the in-vitro study, maximum release was 95.38 ± 4.58% for AZM-NF, 72.79 ± 8.85% for AZM-CP, and 46.13 ± 8.19% for AZM-PD (p < 0.0001). The ex-vivo investigation revealed maximum permeation of 85.68 ± 5.87 for AZM-NF and 64.88 ± 5.87% for AZM-CP (p < 0.001). The in-vivo kinetics showed C 0.738 ± 0.038, and 0.599 ± 0.082 µg/ml with T of 4 and 2 h for AZM-NF and AZM-CP respectively (p < 0.01). Histopathological examination revealed compromised myocardial fibers integrity by AZM-CP only, liver and kidney showed mild aberrations by both formulations, with no remarkable changes in the rest of studied organs. The results showed that AZM-NF exhibited significantly enhanced bioavailability with comparative safer profile to AZM-CP investigated.
阿奇霉素传统制剂的口服生物利用度较差，因此需要开发新的制剂以提高药物的生物利用度。本研究旨在探索新开发的阿奇霉素脂质纳米制剂（AZM-NF）的药代动力学和安全性特征。在体外动力学研究中，采用含有等量 AZM-NF、阿奇霉素市售混悬剂（AZM-CP）或阿奇霉素纯品（AZM-PD）的透析膜评估阿奇霉素的释放。在离体研究中，采用生理盐溶液中的兔肠段在组织浴中进行。在体内研究中，通过给兔口服 AZM，在预定的时间间隔采集血样，然后进行 HPLC 分析。在大鼠中进行毒性研究，观察大鼠内脏器官的组织病理学变化。在体外研究中，AZM-NF 的最大释放度为 95.38 ± 4.58%，AZM-CP 为 72.79 ± 8.85%，AZM-PD 为 46.13 ± 8.19%（p < 0.0001）。离体研究显示 AZM-NF 的最大渗透度为 85.68 ± 5.87%，AZM-CP 为 64.88 ± 5.87%（p < 0.001）。体内药代动力学研究显示，AZM-NF 和 AZM-CP 的 C 0.738 ± 0.038 和 0.599 ± 0.082 µg/ml，T 分别为 4 和 2 h（p < 0.01）。组织病理学检查显示，仅 AZM-CP 会损害心肌纤维的完整性，两种制剂都会导致肝脏和肾脏出现轻微异常，而其余研究器官没有明显变化。结果表明，与 AZM-CP 相比，AZM-NF 具有显著提高的生物利用度和更安全的特性。
