Application of Self-Nanoemulsifying Drug Delivery Systems in Enhancing Dissolution Rate and Pharmacokinetic Performance of Poorly Water-Soluble Pharmaceuticals
Abstract
Poor aqueous solubility remains the single most common cause of variable and incomplete oral absorption among new chemical entities, with a substantial proportion of marketed and pipeline molecules falling under Biopharmaceutics Classification System (BCS) classes II and IV. Self-nanoemulsifying drug delivery systems (SNEDDS) isotropic, anhydrous blends of oil, surfactant and co-surfactant that spontaneously generate droplets below 200 nm on mild agitation in gastrointestinal fluid have emerged as a robust formulation platform to overcome this limitation. In the present work, a model BCS class II drug was formulated into a series of SNEDDS (F1–F9) using a medium-chain lipid, a non-ionic hydrophilic surfactant and a co-surfactant, guided by pseudo-ternary phase diagrams and a simplex-lattice mixture design. The optimized formulation (F7; oil 20%, surfactant–co-surfactant mixture 65%, water 15%) produced a mean droplet size of 61 nm, a polydispersity index of 0.15, a zeta potential of −23.8 mV and greater than 98% transmittance, and remained stable through heating–cooling, centrifugation and freeze–thaw stress testing. In-vitro dissolution in pH 6.8 phosphate buffer showed 99% drug release within 120 minutes from F7, compared with 45% from a physical mixture and 29% from the unformulated drug. Oral administration of F7 in a rodent model produced a 3.3-fold increase in peak plasma concentration and an approximately 2.9-fold increase in the area under the plasma concentration–time curve relative to a conventional aqueous suspension, corresponding to a relative bioavailability of roughly 290%. These findings, considered alongside the wider literature on SNEDDS technology, support the use of lipid-based nanoemulsifying systems as a formulation strategy for enhancing the dissolution rate and oral pharmacokinetic performance of poorly water-soluble pharmaceuticals.