Formulation, characterization, and evaluation of transdermal patches of ranolazine for chronic angina pectoris

Abstract

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/cm²/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_max 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.

Keywords: Angina pectoris; Bioavailability; Ranolazine; Transdermal patches.