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载氟康唑的布洛芬口腔原位凝胶喷雾制剂用于治疗口咽念珠菌病。

Fluconazole-Loaded Ibuprofen In Situ Gel-Based Oral Spray for Oropharyngeal Candidiasis Treatment.

机构信息

Department of Industrial Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand.

Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, 34190, Thailand.

出版信息

AAPS PharmSciTech. 2024 Apr 19;25(5):89. doi: 10.1208/s12249-024-02804-y.

Abstract

Oral candidiasis is a fungal infection affecting the oral mucous membrane, and this research specifically addresses on a localized treatment through fluconazole-loaded ibuprofen in situ gel-based oral spray. The low solubility of ibuprofen is advantageous for forming a gel when exposed to an aqueous phase. The 1% w/w fluconazole-loaded in situ gel oral sprays were developed utilizing various concentrations of ibuprofen in N-methyl pyrrolidone. The prepared solutions underwent evaluation for viscosity, surface tension, contact angle, water tolerance, gel formation, interface interaction, drug permeation, and antimicrobial studies. The higher amount of ibuprofen reduced the surface tension and retarded solvent exchange. The use of 50% ibuprofen as a gelling agent demonstrated prolonged drug permeation for up to 24 h. The incorporation of Cremophor EL in the formulations resulted in increased drug permeation and exhibited effective inhibition against Candida albicans, Candida krusei, Candida lusitaniae, and Candida tropicalis. While the Cremophor EL-loaded formulation did not exhibit enhanced antifungal effects on agar media, its ability to facilitate the permeation of fluconazole and ibuprofen suggested potential efficacy in countering Candida invasion in the oral mucosa. Moreover, these formulations demonstrated significant thermal inhibition of protein denaturation in egg albumin, indicating anti-inflammatory properties. Consequently, the fluconazole-loaded ibuprofen in situ gel-based oral spray presents itself as a promising dosage form for oropharyngeal candidiasis treatment.

摘要

口腔念珠菌病是一种影响口腔黏膜的真菌感染,本研究专门针对通过氟康唑负载布洛芬原位凝胶口腔喷雾进行局部治疗。布洛芬的低溶解度有利于在暴露于水相时形成凝胶。利用 N-甲基吡咯烷酮中不同浓度的布洛芬开发了 1%w/w 的氟康唑负载原位凝胶口腔喷雾。制备的溶液经过粘度、表面张力、接触角、耐水性、凝胶形成、界面相互作用、药物渗透和抗菌研究的评估。更多的布洛芬降低了表面张力并延缓了溶剂交换。使用 50%的布洛芬作为胶凝剂可将药物渗透延长至 24 小时。在制剂中加入 Cremophor EL 导致药物渗透增加,并对白色念珠菌、克柔念珠菌、葡萄牙念珠菌和热带念珠菌表现出有效的抑制作用。虽然含有 Cremophor EL 的制剂在琼脂培养基上没有显示出增强的抗真菌作用,但它促进氟康唑和布洛芬渗透的能力表明在对抗口腔黏膜中念珠菌入侵方面具有潜在的疗效。此外,这些制剂在卵白蛋白中显示出显著的热抑制蛋白质变性,表明具有抗炎特性。因此,氟康唑负载布洛芬原位凝胶口腔喷雾作为治疗口咽念珠菌病的有前途的剂型。

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