Self-nanoemulsifying Drug Delivery System of Cilnidipine

Abstract

Aim: Self-nanoemulsifying Drug Delivery Systems (SNEDDS) are physically stable, isotropic mixtures of oil, surfactant and co-surfactant. The turbulence generated by peristaltic movements of the GIT causes formation of oil-in-water (o/w) nano-emulsions upon dilution. The objective of this study was to improve solubility and oral bioavailability of Cilnidipine by formulating liquid-SNEDDS. Materials and methods: Capmul PG8 NF, Cremophor RH40, and Transcutol HP were selected as oil, surfactant, and co-surfactant. Ternary phase diagrams were constructed to evaluate the nanoemulsification region. A 3 2 factorial design was employed to optimize L-SNEDDS with droplet size and drug release as responses. SNEDDS of CLN was evaluated for droplet size, self-emulsification time, in vitro drug release, ex-vivo permeation, pharmacokinetics and tissue distribution studies and stability studies. The optimized L-SNEDDS was converted into solid form using β-cyclodextrin nanosponges as adsorbents and evaluated in terms of micromeritics, drug content, scanning electron microscopy and powder X-ray diffraction. Results: The optimized batch exhibited droplet size of 23.70 nm, and in vitro drug release of 95.24 % in 60 min.The in-vivo studies revealed nearly 5.53 folds increase in AUC 0-∞ of optimized batch of liquid SNEDDS compared to CLN which can be credited to increase in solubility and dissolution rate. Conclusion: In vivo studies revealed improved pharmacokinetic properties which were attributed to greater surface area and lymphatic absorption leading to circumvention of hepatic first pass metabolism.

Cilnidipine Nanoparticles Oral Film: Preparation and Evaluation

“…It is freely soluble in acetonitrile, sparingly soluble in methanol and in ethanol (99.5), and practically insoluble in water [3]. Combined oxidation state (pKa = 11.39, logP = 5.54), BCS class II (74) , melting point of approximately 110 degrees Celsius, oral bioavailability of approximately 6-30% Mass per mole = 492.52 grams [4]. The challenge of formulating drugs with poor water solubility has been a persistent issue in the pharmaceutical industry, posing a fundamental problem in the optimization of dosage forms Solubility characteristics determine dissolving rate, absorption, and bioavailability [5].…”