In-vitro Lipolysis, Stability and Pharmacodynamic Study of Cilnidipine Loaded Self-emulsifying Drug Delivery System

Abstract

The aim of this research work was to investigate the potential ability of cilnidipineloaded- Self-Emulsifying Drug Delivery System (SEDDS) to improve the solubility and oral bioavailability of cilnidipine. The limited oral bioavailability of BCS class II drugs restricts the clinical utility of drugs. Self-emulsifying drug delivery systems (SEDDS) are widely used for poorly water-soluble drugs to enhance their solubility and oral bioavailability. The therapeutic value of drugs is constrained by the low oral bioavailability of BCS class II drugs. In order to improve the solubility and oral bioavailability of poorly water-soluble drugs, SEDDS are frequently utilised. To develop the cilnidipine-loaded-SEDDS formulation, Canola oil as the oil phase, tween 80 as the surfactant, and PEG 300 as the co-surfactant were used. The SEDDS formulation was evaluated based on stability study per ICH guidelines, drug precipitation during in-vitro lipolysis study under fasted and fed state, and in vivo pharmacodynamic study in Wistar rats. The content of the drug was determined by assay of SEDDS formulation using the official method of cilnidipine. The pharmacodynamic study demonstrated that cilnidipine-loaded SEDDS formulation significantly produced a rapid antihypertensive effect (within 2 h) that lasted for 24 h in comparison to drug suspension. During the in vitro lipolysis study, the concentration of the drug recovered from the aqueous phase under both fasted and fed state was more than 90% after 10 minutes, with a minute amount of drug involved in precipitation. At stability conditions of 30±2 °C/65±5%RH for a duration of six months, the SEDDS formulation was found to be stable. The content of cilnidipine in the SEDDS formulation was found to be 98.4%. A BCS class-II drug's oral bioavailability and dissolution might be improved using the self-emulsifying drug delivery method.