Design, Optimization, and Stability Evaluation of a Self-Nanoemulsifying Drug Delivery System (SNEDDS) to Improve Solubility and Pharmacokinetics of Andrographolide

Poor aqueous solubility and low oral bioavailability significantly limit the therapeutic potential of Andrographolide (AND), a bioactive compound with notable pharmacological effects. This study presents the design and optimization of a novel Self-emulsifying Drug Delivery System (SEDDS) specifically for AND to overcome these limitations by enhancing its pharmacokinetic profile. A systematic excipient screening process was employed, selecting oils, surfactants, and co-surfactants based on their hydrophilic-lipophilic balance (HLB). The optimized AND-loaded SEDDS was identified using critical quality attributes, including droplet size (<150 nm), polydispersity index (≤0.25), transmittance (>80%), and drug content in distilled water, 0.1 mM HCl, and simulated intestinal fluid. Oral bioavailability was assessed through in vivo pharmacokinetic studies in Sprague Dawley rats. The selected formulation, composed of 11.11% castor oil, 71.11% cremophor RH40, and 17.78% span 20, met the required criteria of optimum DS, PdI, T%, and contained the highest drug loading (7.45 mg/mL). The optimized formulation showed improved drug release in the in vitro dissolution study and an 8-fold increase in in vivo pharmacokinetic study compared with pure AND. The AND-SEDDs remained stable profile during the short-term study and at three different storage conditions. SEDDs are an effective lipid-based strategy to overcome the poor solubility and low bioavailability issues for oral drugs, which also offer a promising approach for BCS Class II drug development in the future.