Design and Development of Self-nanoemulsifying Drug Delivery System (SNEDDS) with Morin Hydrate to Enhance Nimodipine’s oral Bioavailability and Pharmacokinetics

Abstract

Nimodipine (NMD), a calcium channel blocker, is classified as a Biopharmaceutical Classification System Class II drug, with low oral bioavailability (3%–30%) due to extensive first-pass metabolism. Self-nanoemulsifying drug delivery systems (SNEDDS) offer a novel approach to improving the bioavailability of such drugs. Morin hydrate (MH), a flavonoid, may enhance NMD’s bioavailability by modulating CYP3A4 and P-glycoprotein during metabolism. This study aimed to optimize an MH-loaded NMD-SNEDDS formulation using a three-factor, three-level Box–Behnken design (BBD). Independent variables were Capmul MCM (X1) as the oil, Cremophor RH-40 (X2) as the surfactant, and Transcutol-P (X3) as the co-surfactant. Dependent variables included droplet size (Y1), polydispersity index (Y2), and cumulative drug release in 15 minutes (Y3). The optimized formulation (X1 = 10.0 mg, X2 = 62.0 mg, X3 = 40.0 mg) predicted Y1, Y2, and Y3 values of 124.3 nm, 0.105, and 97.2%, respectively, with a desirability of 0.885 0. Pharmacokinetic studies showed that NMD-SNEDDS and MH-loaded NMD-SNEDDS increased oral bioavailability 3-fold and 4-fold, respectively, compared to pure drug suspension. MH-loaded NMD-SNEDDS demonstrated P-gp inhibition, enhancing NMD absorption. BBD effectively optimized the SNEDDS formulation, and MH-loaded NMD-SNEDDS is a promising approach to enhance NMD’s oral bioavailability.