Design And Development of Cilnidipine-Loaded Transdermal Nanoemulsion and Nanoemulsion Gel for the Management of Hypertension

Abstract

**Background:** Hypertension requires long-term pharmacotherapy, and many anti-hypertensive drugs undergo extensive hepatic first-pass metabolism that limits oral bioavailability. Cilnidipine, a dihydropyridine calcium channel blocker with renoprotective and cardioprotective actions, is a Biopharmaceutics Classification System (BCS) Class II drug with low aqueous solubility and reduced oral bioavailability due to first-pass metabolism. **Objectives:** To design a transdermal nanoemulsion and nanoemulsion gel of cilnidipine to bypass first-pass metabolism, enhance solubility and improve bioavailability. **Materials and Methods:** Caproyl 90-Triacetin (1:1), Labrasol and Transcutol P were selected as oil, surfactant and co-surfactant respectively on the basis of maximum drug solubility. Pseudo-ternary phase diagrams were constructed by water titration at seven Smix ratios, and three thermodynamically stable formulations (NF1-NF3) were characterized for droplet size, zeta potential, ex-vivo permeation (excised goat skin, Franz cell), in-vitro release kinetics and International Council for Harmonisation (ICH)-guided stability; the optimised nanoemulsion was incorporated into a Carbopol 934 gel. **Results:** NF2 (Smix 3:1) showed a mean droplet size of 128.3 nm, polydispersity index 0.211 and zeta potential 78.6 mV. Ex-vivo permeation reached 47.54% over 24 h (flux 173.84 µg/cm²/h); in-vitro release followed zero-order kinetics (R² = 0.808); drug content remained ≥96% after 90 days at 25 °C/60% relative humidity (RH), with an estimated shelf-life of ~15 months. The nanoemulsion gel showed satisfactory pH, viscosity, gel strength and swelling index. **Conclusion:** The cilnidipine nanoemulsion and nanoemulsion gel represent a viable transdermal alternative to oral therapy for the chronic management of hypertension.