Aratwar Ashwini, Maji Indrani, Chilvery Shrilekha, Mahajan Srushti, Aalhate Mayur, Gupta Ujala, Godugu Chandraiah, Singh Pankaj Kumar
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, India.
Department of Biological Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, India.
AAPS PharmSciTech. 2024 Dec 13;26(1):12. doi: 10.1208/s12249-024-03003-5.
Tyrosine kinase inhibitors like tofacitinib (TCB), are excellent examples of small molecular compounds that have demonstrated success in treating psoriasis. The current study aims to improve the efficacy of TCB and reduce its systemic adverse effects by developing a topical w/o emulgel formulation that will ameliorate the anti-psoriatic activity in a model of Imiquimod-induced BALB/c mice. In order to create w/o emulgel, the TCB was incorporated into the w/o emulsion using Peppermint oil, Transcutol P, and PEG-200 followed by converted into a gel by adding Carbopol 940. The final formulation was optimized by applying a 3-level, 3-factor Box-Behnken Design (BBD). The optimized formulation showed a viscosity of 560606.6 ± 80.8 cps (560 Pa.S), and firmness of 356 ± 48 g, and that was within the acceptable range with respect to the marketed emulgel preparation available for topical application. The developed TCB-emulgel also exhibited a controlled release profile, with 68.26 ± 8.33% release of TCB over 24 h and a 5-fold greater skin permeation as compared to normal TCB-gel. Apart from that, the application of TCB-emulgel on the diseased model results in a 3.3-times reduction in the PASI (Psoriasis Area Severity Index) scoring. Lastly, the epidermal reduction in histopathological evaluation, along with the reduction in TNF-α and Ki-67 levels observed in immunostaining, ensures the enhanced anti-psoriatic effect of the developed TCB-emulgel in comparison to the marketed product. To put it briefly, the findings of the study and the therapeutic effectiveness of the developed TCB-emulgel provide a strong basis for the clinical management of psoriasis in the future.
酪氨酸激酶抑制剂如托法替布(TCB),是在治疗银屑病方面取得成功的小分子化合物的优秀范例。当前的研究旨在通过开发一种外用油包水型乳胶制剂来提高TCB的疗效并降低其全身不良反应,该制剂将改善咪喹莫特诱导的BALB/c小鼠模型中的抗银屑病活性。为了制备油包水型乳胶,将TCB与薄荷油、肉豆蔻酸异丙酯和聚乙二醇 - 200一起加入油包水型乳液中,然后通过添加卡波姆940转化为凝胶。最终制剂通过应用三水平、三因素的Box - Behnken设计(BBD)进行优化。优化后的制剂粘度为560606.6 ± 80.8 cps(560 Pa·S),硬度为356 ± 48 g,相对于市售的外用乳胶制剂而言,该粘度和硬度在可接受范围内。所开发的TCB乳胶还呈现出控释特性,24小时内TCB的释放率为68.26 ± 8.33%,与普通TCB凝胶相比,皮肤渗透率提高了5倍。除此之外,在患病模型上应用TCB乳胶可使银屑病面积和严重程度指数(PASI)评分降低3.3倍。最后,组织病理学评估中表皮厚度的降低,以及免疫染色中观察到的肿瘤坏死因子 - α和Ki - 67水平的降低,确保了所开发的TCB乳胶与市售产品相比具有更强的抗银屑病效果。简而言之,该研究结果以及所开发的TCB乳胶的治疗效果为未来银屑病的临床管理提供了有力依据。