Pacific Academy of Higher Education and Research, Udaypur, Rajasthan, India; Department of Pharmaceutics, Genesis Institute of Pharmacy, Sonyachi Shiroli, 416212 Radhanagari, Kolhapur Maharashtra, India.
Tatyasaheb Kore College of Pharmacy, Warananagar, 416113 Panhala, Kolhapur Maharashtra, India.
Ann Pharm Fr. 2022 Mar;80(2):157-168. doi: 10.1016/j.pharma.2021.05.004. Epub 2021 May 21.
The chief objective of the present research was to reduce local side effects by reducing the dose, controlling the release, and improving the stability by developing and optimizing tretinoin (TRT)-loaded topical emulgel formulation.
TRT emulgel (TE) was prepared and optimized at varying ratios of excipients and using 3 optimal response surface design (ORSD). The TRT emulgel was optimized based on TRT content and in vitro release profile of TRT from formulated emulgel batches. The optimized TRT was characterized for physical properties, pH, viscosity, spreadability, extrudability, photomicroscopy, in vitro anti-acne, in vivo skin irritation, in vivo anti-inflammatory activity, and stability study.
The FTIR and DSC analysis revealed the compatibility between TRT and formulation excipients of emulgel. The batch F5 of emulgel formulation displayed maximum drug content (98.69±1.26%), and controlled TRT release (78.27±0.69%). Thus, batch F5 was selected as an optimized batch for further characterization. The photomicroscopic analysis of optimized TE exhibited the presence of spherical globules. The pH and viscosity of optimized TE were found to be 6.20±0.12 and 3240cP respectively. Besides, the optimized TE showed good spreadability and extrudability. The in vitro anti-acne activity against Propionibacterium acne (P. acne) of optimized TE (diameter of zone of inhibition 34.54±0.26mm) was found to be the comparatively same as that of marketed Sotret® gel (diameter of zone of inhibition 36.13±0.43mm). Moreover, no sign of irritation was observed in rats treated with optimized TE indicating the safety of TE. Furthermore, the optimized TE displayed significant (p<0.01) in vivo anti-inflammatory activity when compared to marketed gel. Besides, optimized TE was found to be stable when stored in cool conditions for three months.
Thus, the emulgel could be a promising approach for the topical delivery of TRT with improved performance and reduced side effects.
本研究的主要目的是通过开发和优化含有维 A 酸（TRT）的局部透皮乳膏剂来减少局部副作用，降低剂量、控制释放并提高稳定性。
通过改变赋形剂的比例并使用 3 个最佳响应面设计（ORSD）来制备和优化 TRT 乳凝胶（TE）。根据 TRT 含量和配方乳凝胶批次中 TRT 的体外释放情况优化 TRT 乳凝胶。对优化后的 TRT 进行物理性质、pH 值、粘度、铺展性、挤出性、光镜、体外抗痤疮、体内皮肤刺激性、体内抗炎活性和稳定性研究。
傅里叶变换红外光谱（FTIR）和差示扫描量热法（DSC）分析表明 TRT 与乳凝胶赋形剂之间具有相容性。乳凝胶制剂的 F5 批显示出最大药物含量（98.69±1.26%）和控制 TRT 释放（78.27±0.69%）。因此，选择 F5 批作为进一步表征的优化批。优化后的 TE 的光镜分析显示存在球形液滴。优化后的 TE 的 pH 值和粘度分别为 6.20±0.12 和 3240cP。此外，优化后的 TE 具有良好的铺展性和挤出性。优化后的 TE 对痤疮丙酸杆菌（P. acne）的体外抗痤疮活性（抑菌圈直径 34.54±0.26mm）与市售 Sotret®凝胶（抑菌圈直径 36.13±0.43mm）相当。此外，用优化后的 TE 处理的大鼠未观察到刺激迹象，表明 TE 安全。此外，与市售凝胶相比，优化后的 TE 显示出显著的（p<0.01）体内抗炎活性。此外，优化后的 TE 在储存在凉爽条件下三个月后被发现是稳定的。
因此，乳凝胶可能是一种有前途的局部递送 TRT 的方法，具有改善的性能和减少的副作用。
