Department of Pharmaceutics, Sinhgad College of Pharmacy, Pune, 411041, Maharashtra, India.
AAPS PharmSciTech. 2013 Mar;14(1):101-10. doi: 10.1208/s12249-012-9893-1. Epub 2012 Dec 11.
In order to improve the bioavailability of the antidepressant drug, venlafaxine hydrochloride, in situ mucoadhesive thermoreversible gel, was formulated using Lutrol F127 (18%) as a thermo gelling polymer. Mucoadhesion was modulated by trying carbopol 934, PVP K30, HPMC K4M, sodium alginate, tamarind seed gum, and carrageenan as mucoadhesive polymers. Results revealed that as the concentration of mucoadhesive polymer increased the mucoadhesive strength increased but gelation temperature decreased. Formulation was optimized on the basis of clarity, pH, gelation temperature, mucoadhesive strength, gel strength, viscosity, drug content, diffusion through sheep nasal mucosa, histopathological evaluation of mucosa, and pharmacodynamic study in rats. Final formulation T5 containing 18% Lutrol F127 and 0.3% PVP K30 was considered as an optimized formulation. T5 released 97.86±0.073% drug in 150 min with a flux of 0.1545 mg cm(-2) min(-1) and gelation temperature 31.17±0.30°C. Histopathological evaluation of nasal mucosa revealed that T5 formulation was safe for nasal administration as it caused no damage to nasal epithelium. From the results of pharmacodynamic study, mainly forced swim test (FST), it was concluded that venlafaxine hydrochloride was more effective as an antidepressant by nasal route as in situ gel nasal drops in comparison to oral administration of equivalent dose.
为了提高抗抑郁药盐酸文拉法辛的生物利用度，采用 Lutrol F127（18%）作为热凝胶聚合物，制备了原位黏膜黏附热可逆凝胶。通过尝试卡波姆 934、PVP K30、HPMC K4M、海藻酸钠、罗望子胶和卡拉胶作为黏膜黏附聚合物来调节黏膜黏附性。结果表明，随着黏膜黏附聚合物浓度的增加，黏膜黏附强度增加，但凝胶温度降低。根据澄清度、pH 值、凝胶温度、黏膜黏附强度、凝胶强度、黏度、药物含量、通过绵羊鼻黏膜的扩散、黏膜的组织病理学评价以及大鼠药效学研究对制剂进行了优化。最终的配方 T5 含有 18%的 Lutrol F127 和 0.3%的 PVP K30，被认为是优化的配方。T5 在 150 分钟内释放 97.86±0.073%的药物，通量为 0.1545mg·cm-2·min-1，凝胶温度为 31.17±0.30°C。鼻黏膜的组织病理学评价表明，T5 配方作为鼻内给药是安全的，因为它不会对鼻上皮造成损伤。从药效学研究的结果，主要是强迫游泳试验（FST），可以得出结论，与口服等效剂量相比，盐酸文拉法辛通过鼻内途径作为原位凝胶滴鼻剂作为抗抑郁药更有效。
