Momin Zubair, D Manjula, B Premakumari K, K Vijaya Bhaskar, Kumar Lalit
Department of Pharmaceutics, College of Pharmaceutical Sciences, Dayananda Sagar University, Bengaluru, Karnataka, India.
Department of Pharmaceutical Chemistry, College of Pharmaceutical Sciences, Dayananda Sagar University, Bengaluru, Karnataka, India.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Aug 18. doi: 10.1007/s00210-025-04504-1.
T his study is aimed at developing and evaluating matrix-type transdermal patches of ranolazine (Rn) to enhance its bioavailability and therapeutic efficacy in chronic angina pectoris. Patches were formulated using the mercury substrate method with polymers such as ethyl cellulose, HPMC, PMMA, and sodium alginate. Among the twelve formulations, F6 was optimized based on physical and other performance parameters. The F6 patches showed a drug content of 96.44 ± 0.15%, thickness of 0.227 ± 0.11 mm, weight of 106.90 ± 0.03 mg, and folding endurance of 94 ± 0.19. Moisture loss and water vapor transmission rate were found to be 4.92 ± 0.03% and 0.00043 ± 0.05 g/cm/h, respectively. In vitro drug release for F6 was 91.50 ± 0.14% at 24 h, and ex vivo permeation through rat skin was 87.92 ± 0.32% after 24 h. SEM confirmed uniform drug distribution, and no signs of irritation were observed in skin irritation tests. Stability studies over 60 days indicated minimal changes (less than 3%) in drug content. Pharmacokinetic analysis demonstrated that F6 achieved a C of 1264.44 µg/mL and AUC₀-₂₄ of 39,894.35 µg·h/mL, compared to 1037.04 µg/mL and 23,827.17 µg·h/mL for oral ranolazine, indicating a 1.67-fold increase in bioavailability. Biodistribution studies showed higher drug accumulation in the heart (378.20 µg/mL) versus oral (236.11 µg/mL), with reduced liver exposure, indicating decreased first-pass metabolism. These findings suggest that the developed Rn transdermal patch offers a promising alternative to oral administration by improving bioavailability and target tissue delivery.
本研究旨在开发和评估雷诺嗪（Rn）的基质型透皮贴剂，以提高其在慢性心绞痛中的生物利用度和治疗效果。采用汞基质法，使用乙基纤维素、羟丙甲纤维素、聚甲基丙烯酸甲酯和海藻酸钠等聚合物制备贴剂。在12种制剂中，根据物理和其他性能参数对F6进行了优化。F6贴剂的药物含量为96.44 ± 0.15%，厚度为0.227 ± 0.11毫米，重量为106.90 ± 0.03毫克，耐折性为94 ± 0.19。发现水分损失和水蒸气透过率分别为4.92 ± 0.03%和0.00043 ± 0.05克/厘米/小时。F6在24小时的体外药物释放率为91.50 ± 0.14%，24小时后通过大鼠皮肤的离体渗透率为87.92 ± 0.32%。扫描电子显微镜证实药物分布均匀，皮肤刺激性试验未观察到刺激迹象。60天的稳定性研究表明药物含量变化极小（小于3%）。药代动力学分析表明，F6的Cmax为1264.44微克/毫升，AUC₀-₂₄为39894.35微克·小时/毫升，而口服雷诺嗪分别为1037.04微克/毫升和23827.17微克·小时/毫升，表明生物利用度提高了1.67倍。生物分布研究表明，与口服（236.11微克/毫升）相比，心脏中的药物蓄积更高（378.20微克/毫升），肝脏暴露减少，表明首过代谢降低。这些发现表明，所开发的Rn透皮贴剂通过提高生物利用度和靶向组织递送，为口服给药提供了一种有前景的替代方案。
