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

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 (<i>X</i>₁) as the oil, Cremophor RH-40 (<i>X</i>₂) as the surfactant, and Transcutol-P (<i>X</i>₃) as the co-surfactant. Dependent variables included droplet size (<i>Y</i>₁), polydispersity index (<i>Y</i>₂), and cumulative drug release in 15 minutes (<i>Y</i>₃). The optimized formulation (<i>X</i>₁ = 10.0 mg, <i>X</i>₂ = 62.0 mg, <i>X</i>₃ = 40.0 mg) predicted <i>Y</i>₁, <i>Y</i>₂, and <i>Y</i>₃ values of 124.3 nm, 0.105, and 97.2%, respectively, with a desirability of 0.8850. 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.