Solidified SEDDS for improved stability of papain: Freeze drying and stabilization via hydrophobic ion pairing

In this study, a hydrophobic ion pairing (HIP) and solidification approach was used to develop a solid self-emulsifying drug delivery system (S-SEDDS) for improving the stability of papain. In this case, Papain was mixed with sodium deoxycholate (SD) in a 1:20 molar ratio to form HIP-complex. Liquid SEDDS (L-SEDDS) formulations include Capmul MCM (oil phase), Tween 80 (surfactant), and Transcutol HP (cosurfactant). SEDDS-HIP (F1) displayed a zeta potential of −27.7 ± 0.12 mV, a polydispersity index (PDI) of 0.249 ± 0.03, and a particle size of 164 ± 0.86 nm, demonstrating good stability and uniformity; therefore, selected for performing solidification. The solid SEDDS-HIP exhibits excellent flowability, compressibility, and better micromeritic attributes, encompassing an angle of repose of 23.29 ± 0.15° and a Carr’s Index of 8.4 ± 0.2%, highlighting improved flow and packing behavior. The dissolution experiment showed that the drug was almost entirely released in 30 minutes, which means the enhanced drug release behavior of Solid SEDDS-HIP. Further, the structural stability and homogeneous distribution of the HIP complex in the solid SEDDS-HIP were confirmed by ATR, DSC, PXRD, and SEM analyses. Overall, the study explores the potential of solid SEDDS-HIP for enhancing the stability of hydrophobic enzymes and drug release kinetics, offering a robust platform for advanced drug delivery applications.