- Strategic design for enhanced pain treatment: developing an oral self-nanoemulsifying system.

ARRIGONI-RODRÍGUEZ, KA; OLIVERA, ME; LUCIANI GIACOBBE LC

Congreso; 7ma Reunión Internacional de Ciencias Farmacéuticas; 2023

A novel oral pharmaceutical composition of morphine (MOR) and omega-3 fatty acids (O3)generated a synergistic analgesic effect and reduced adverse events associated with MORin a murine model (patent P-20120100854). Considering that a self-nanoemulsifying drugdelivery system (SNEDDS) could enhance the oral absorption of O3, this study aimed tooptimize a MOR-O3-loaded SNEDDS composition, maximizing the loading capacity of theoil phase.First, the limits of each component in the blank SNEDDS were explored using pseudo-ternary phase diagrams to then optimize them by means of a D-Optimal design, usingethanol, propylene glycol (Pg), kolliphor (K), and the oily phase (krill oil, AK) asindependent variables. The key responses measured were polydispersity index (PDI) andmean droplet size (nm). Mathematical models were used to establish correlationsbetween variables and responses, and a desirability function was applied to determine theoptimal formulation (PDI ≤ 0.2 and smaller size).After optimization, component limits were adjusted for MOR-O3 loaded SNEDDS, whichwere evaluated similarly to blank SNEDDS, using Pg, K, and the oily phase: AK + MOR-O3as independent variables. The predictive capability of the design space was confirmedwith two independent optimized formulations, comparing obtained and predictedresponses.Both the PDI and droplet size of blank SNEDDS and MOR-O3-loaded SNEDDS fittedsignificant mathematical models, defining design spaces.The most desirable blank SNEDDS formulation contained 28% Pg, 50% K, and 22% AKwhile the one loaded with MOR-O3 contained 33% Pg, 45% K, and 22% of oily phase, beingtransparent and of low flow with a droplet size of (15 ± 8) nm and PDI of 0.17 ± 0.05. Inaddition, it allowed the loading of MOR in the oily phase used in previous preclinicalstudies. In conclusion, this study offers a robust and predictive approach for developingMOR-O3 loaded SNEDDS suitable for future pain treatment applications.