Abstract

FORMULATION AND EVALUATION OF CILNIDIPINE LOADED NANOPARTICLE FOR TRANSDERMAL PATCH

Dr. Shahid Mohammed*, Abdul Muhtasib Khan*, MD. Aamir Hussain*

ABSTRACT

This work presents the formulation and evaluation of cilnidipine-loaded polymeric nanoparticles embedded in a transdermal patch to achieve effective, sustained, and patient-friendly management of hypertension. Cilnidipine, a BCS class II calcium channel blocker with poor aqueous solubility and low oral bioavailability, was selected as a candidate for nanoparticle-based transdermal delivery to bypass first-pass metabolism, enhance bioavailability, and reduce dosing-related side effects. Polymeric nanoparticles were prepared using PLGA as the carrier polymer by a solvent evaporation technique, and the process parameters were optimized to obtain nanosized, stable dispersions suitable for incorporation into a film-forming matrix. A series of nanoparticle formulations (F1–F8) were developed and characterized for particle size, polydispersity index, zeta potential, morphology, and entrapment efficiency using optical microscopy, zeta analysis, SEM, and UV–visible spectrophotometry. The optimized batch, F4, exhibited a mean particle size of about 75 nm and a zeta potential of approximately −27 mV, indicating good colloidal stability and suitability for controlled release applications. These optimized nanoparticles were then dispersed into polymeric film systems composed mainly of HPMC E15, ethylcellulose, PEG, and DMSO to fabricate nanoparticle-loaded transdermal patches via solvent casting and room-temperature drying. The prepared patches were evaluated for physical appearance, thickness, weight uniformity, folding endurance, tensile strength, and drug content to ensure mechanical robustness and dose uniformity. Among the various film formulations (F1–F8), the F8 patch containing optimized nanoparticles showed the most desirable balance of mechanical properties, uniform drug content, and ease of handling. In vitro drug release and permeation studies were carried out using Franz diffusion cells with phosphate buffer pH 7.4 as receptor medium at 37 ± 0.5 °C, under sink conditions. The optimized nanoparticle-loaded patch provided nearly complete release, with cumulative drug release reaching around 99.79% within 12 hours, demonstrating its capability for extended and controlled delivery of cilnidipine through the skin. Release kinetic analysis revealed that the system followed zero-order kinetics with a good fit to the Korsmeyer–Peppas model, indicating predominantly diffusion-controlled release with an approximately constant rate over the study period. Stability studies conducted on the optimized patch (stored at 4 ± 1 °C and 26 ± 2 °C for up to 90 days) showed minimal changes in drug content, folding endurance, physical appearance, and cumulative drug release, confirming the physical and chemical stability of the formulation. Collectively, the findings demonstrate that PLGA-based cilnidipine nanoparticles incorporated into a transdermal patch can provide a promising alternative to conventional oral therapy by improving release control, potentially enhancing bioavailability, and offering a non-invasive, once-daily approach for long-term antihypertensive treatment.

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