Darwesh Bayan, Aldawsari Hibah M, Badr-Eldin Shaimaa M
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Pharmaceutics. 2018 Nov 12;10(4):227. doi: 10.3390/pharmaceutics10040227.
(1) Background: Fluconazole, used orally for vaginal candidiasis, has reported gastrointestinal side effects. Therefore, researchers directed towards the drug vaginal delivery. However, vaginal delivery is limited by poor retention and leakage. Thus, this work aimed at exploring chitosan/anion polyelectrolyte complex (PEC) for the formulation of fluconazole vaginal inserts with controlled release and appreciable mucoadhesion. (2) Methods: PECs were prepared and assessed for interactions. Fluconazole PEC based vaginal inserts were prepared by lyophilization using mannitol. 3¹5¹ factorial design was applied to investigate the effect of the anion type and Chitosan/anion ratio on the inserts mucoadhesion and release properties. The optimized insert [based on 5:5 chitosan: anionic polymer (sodium alginate)] release was modulated by the release retardant; Compritol 888. The selected formulation was subjected to microbiological and histological evaluation. (3) Results: Fluconazole inserts showed satisfactory drug content, acceptable friability percentages and highest swelling indices at six hours. Statistical analysis showed significant effect of the studied factors on detachment force and release properties. Microbiological assays revealed significantly higher antifungal activity of inserts compared to fluconazole solution. Reduced inflammatory cells were confirmed by histological evaluation. (4) Conclusion: CH/Alg based vaginal insert could be a promising platform for vaginal delivery of antifungal drugs used for vaginal candidiasis treatment.
(1) 背景：口服用于治疗阴道念珠菌病的氟康唑有胃肠道副作用的报道。因此，研究人员致力于该药物的阴道给药。然而，阴道给药受限于药物滞留性差和泄漏问题。因此，本研究旨在探索壳聚糖/阴离子聚电解质复合物（PEC）用于制备具有控释和良好粘膜粘附性的氟康唑阴道栓剂。(2) 方法：制备PEC并评估其相互作用。以甘露醇为冻干保护剂，通过冻干法制备基于氟康唑PEC的阴道栓剂。采用3¹5¹析因设计研究阴离子类型和壳聚糖/阴离子比例对栓剂粘膜粘附性和释放性能的影响。通过释放阻滞剂Compritol 888调节优化后的栓剂（基于壳聚糖：阴离子聚合物（海藻酸钠）比例为5:5）的释放。对所选制剂进行微生物学和组织学评价。(3) 结果：氟康唑栓剂药物含量令人满意，脆碎度百分比可接受，在6小时时溶胀指数最高。统计分析表明，所研究因素对分离力和释放性能有显著影响。微生物学测定显示，栓剂的抗真菌活性明显高于氟康唑溶液。组织学评价证实炎症细胞减少。(4) 结论：基于壳聚糖/海藻酸钠的阴道栓剂可能是用于治疗阴道念珠菌病的抗真菌药物阴道给药的一个有前景的平台。
