Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka State, India.
Department of Pharmacy, Lloyd Institute of Management and Technology, Plot No.11, Knowledge Park-II, Greater Noida 201306, Uttar Pradesh, India.
Curr Mol Med. 2024;24(11):1317-1328. doi: 10.2174/0115665240291343240306054318.
Pregabalin (PG) and diclofenac diethylamine (DEE) are anti-inflammatory molecules that are effective in relieving inflammation and pain associated with musculoskeletal disorders, arthritis, and post-traumatic pain, among others. Intravenous and oral delivery of these two molecules has their limitations. However, the transdermal route is believed to be an alternate viable option for the delivery of therapeutic molecules with desired physicochemical properties. To this end, it is vital to understand the physicochemical properties of these drugs, dosage, and strategies to enhance permeation, thereby surmounting the associated constraints and concurrently attaining a sustained release of these therapeutic molecules when administered in combination. The present work hypothesizes the enhanced permeation and sustained release of pregabalin and diclofenac diethylamine across the skin, entrapped in the adhesive nano-organogel formulation, including permeation enhancers. The solubility studies of pregabalin and diclofenac diethylamine in combination were performed in different permeation enhancers. Oleic acid was optimized as the best permeation enhancer based on studies. Pluronic organogel containing pregabalin and diclofenac diethylamine with oleic acid was fabricated. Duro-Tak (87-2196) was added to the organogel formulation as a pressure-sensitive adhesive to sustain the release profile of these two therapeutic molecules. The adhesive organogel was characterized for particle size, scanning electron microscopy, and contact angle measurement. The HPLC method developed for the quantification of the dual drug showed a retention time of 3.84 minutes and 9.69 minutes for pregabalin and diclofenac, respectively. The fabricated nanogel adhesive formulation showed the desired results with particle size and contact angle of 282 ± 57 nm and ≥120⁰, respectively. studies showed the percentage cumulative release of 24.90 ± 4.65% and 33.29 ± 4.81% for pregabalin and diclofenac, respectively. In order to accomplish transdermal permeation, the suggested hypothesis of fabricating PG and DEE nano-organogel in combination with permeation enhancers will be a viable drug delivery method. In comparison to a traditional gel formulation, oleic acid as a permeation enhancer increased the penetration of both PG and DEE from the organogel formulation. Notably, the studies showed that the use of pressure-sensitive adhesives enabled the sustained release of both PG and DEE.Therefore, the results anticipated the hypothesis that the transdermal delivery of adhesive PG and DEEbased nanogel across the human skin can be achieved to inhibit inflammation and pain.
普瑞巴林（PG）和双氯芬酸二乙胺（DEE）是两种抗炎分子，它们可有效缓解与肌肉骨骼疾病、关节炎和创伤后疼痛等相关的炎症和疼痛。这两种分子的静脉内和口服给药都存在局限性。然而，透皮途径被认为是具有所需物理化学特性的治疗分子给药的另一种可行选择。为此，了解这些药物的物理化学性质、剂量以及增强渗透的策略至关重要，从而克服相关限制，并在联合用药时实现这些治疗分子的持续释放。本工作假设将普瑞巴林和双氯芬酸二乙胺包封在粘性纳米有机凝胶制剂中，并结合渗透增强剂，可增强其穿过皮肤的渗透和持续释放。研究了普瑞巴林和双氯芬酸二乙胺在不同渗透增强剂中的溶解度。基于研究，优化了油酸作为最佳渗透增强剂。制备了含有普瑞巴林和双氯芬酸二乙胺与油酸的泊洛沙姆有机凝胶。将 Duro-Tak（87-2196）添加到有机凝胶制剂中作为压敏胶，以维持这两种治疗分子的释放曲线。对粘性有机凝胶进行了粒径、扫描电子显微镜和接触角测量。为定量测定这两种药物而开发的 HPLC 方法显示普瑞巴林和双氯芬酸的保留时间分别为 3.84 分钟和 9.69 分钟。所制备的纳米凝胶粘性制剂的粒径和接触角分别为 282±57nm 和≥120°，达到了预期的结果。研究显示，普瑞巴林和双氯芬酸的累积释放百分比分别为 24.90±4.65%和 33.29±4.81%。为了实现经皮渗透，将普瑞巴林和双氯芬酸纳米有机凝胶与渗透增强剂联合制备的假设将是一种可行的药物输送方法。与传统凝胶制剂相比，作为渗透增强剂的油酸增加了从有机凝胶制剂中渗透出的普瑞巴林和双氯芬酸的量。值得注意的是，研究表明，使用压敏胶可以实现普瑞巴林和双氯芬酸的持续释放。因此，研究结果证实了这样一种假设，即通过皮肤递送粘性 PG 和 DEE 基于纳米凝胶可以抑制炎症和疼痛。
