Self-emulsifying Drug Delivery System for Praziquantel with Enhanced Ex Vivo Permeation

Purpose In this work, praziquantel (PZQ) was incorporated into self-emulsifying drug delivery system (SEDDS) formulations to demonstrate that the increased apparent solubility and dissolution rate enhance intestinal permeation. Methods Solubility measurements of PZQ were performed in lipid excipients and hydrophilic substances; ternary phase diagrams were constructed with the excipients in which PZQ showed increased solubility. SEDDS formulations were characterized by globule size, the polydispersity index, zeta potential, the self-emulsification time, and morphology by scanning and transmission electron microscopy. The formulations were evaluated by performing in vitro dissolution profiles and permeation profiles in an ex vivo model. Results Four SEDDS formulations were identified that increased the apparent solubility of praziquantel by 60-150 times. The dispersion sizes obtained were < 350 nm, with polydispersity index values < 0.3, dispersion times < 60 s, and zeta potential values < -25 mV. A notable increase in the PZQ dissolution rate was obtained compared with the reference drug product. The permeation profiles were adjusted to a first-order kinetic model, obtaining an apparent absorption rate constant (K-ab) up to 18 times higher for SEDDS formulations than for PZQ powder, while the apparent permeability (P-app) and the effective intestinal permeability (P-eff) values increased up to 18 times for SEDDS formulations compared with PZQ powder. Conclusion The incorporation of PZQ into a SEDDS increases its apparent solubility and dissolution rate, changes that significantly enhance the processes of intestinal permeability. This behavior can be applied to support formulations of drugs belonging to class IV of the biopharmaceutical classification system.