Dental and Craniofacial Trauma Research and Tissue Regeneration, US Army Institute of Surgical Research, 3650 Chambers Pass, JBSA Fort Sam, Houston, Texas, 78234-7767, USA.
Department of Drug Sciences, University of Pavia, V.le Taramelli 12, 27100, Pavia, Italy.
AAPS PharmSciTech. 2018 Jul;19(5):2264-2275. doi: 10.1208/s12249-018-1030-3. Epub 2018 May 11.
The purpose of this study was to develop pirfenidone (PF) ointment formulations for a dose finding study in the prophylactic treatment of deep partial-thickness burns in a mouse model. A preformulation study was performed to evaluate the solubility of PF in buffers and different solvents and its stability. Three different formulations containing 1, 3.5, and 6.5% w/w PF were prepared and optimized for their composition for testing in mice. Optimized formulations showed promising in vitro release profiles, in which 20-45% of PF was released in the first 7 h and 70-90% released within 48 h. The rheological properties of the ointment remained stable throughout storage at 25 ± 2°C/60% RH. Animal studies showed treatments of burn wounds during the inflammatory stage of wound healing with PF ointments at different drug concentrations had no adverse effects on reepithelization. Moreover, 6.5% PF ointment (F3) reduced the expression of pro-inflammatory cytokines IL-12p70 and TNFα. This study suggests that hydrocarbon base ointment could be a promising dosage form for topical delivery of PF in treatment of deep partial-thickness burns.
本研究旨在开发吡非尼酮（PF）软膏制剂，用于在小鼠模型中进行预防性治疗深度部分厚度烧伤的剂量发现研究。进行了预配方研究以评估 PF 在缓冲液和不同溶剂中的溶解度及其稳定性。制备了包含 1%、3.5%和 6.5%w/w PF 的三种不同制剂，并对其组成进行了优化，以用于在小鼠中进行测试。优化的制剂显示出有前途的体外释放曲线，其中在最初的 7 小时内释放了 20-45%的 PF，在 48 小时内释放了 70-90%。软膏的流变学性质在 25±2°C/60%RH 下的整个储存过程中保持稳定。动物研究表明，在创面愈合的炎症期，用不同药物浓度的 PF 软膏处理烧伤创面，对再上皮化没有不良影响。此外，6.5%PF 软膏（F3）降低了促炎细胞因子 IL-12p70 和 TNFα 的表达。这项研究表明，烃基软膏可能是治疗深度部分厚度烧伤中 PF 局部递送的有前途的剂型。
