Development of long-acting intramuscular vortioxetine pamoate suspensions: Formulation optimization and...

This study aims to develop a long-acting intramuscular vortioxetine pamoate (VTXP) suspensions and evaluate their pharmacokinetic profiles. VTXP suspensions stabilized by Tween 20, Soluplus and poloxamer were prepared using Planetary Ball Mill at lab-scale to identify an optimal stabilizer. Pilot-scale batches were then evaluated by varying drug loading, bead quantity, and bead size to optimize milling pressure and cycle. The VTXP suspensions were characterized by laser diffraction (LD) for particle size analysis, viscosity measurement, injection force tests, X-ray Powder Diffraction (XRPD) for solid-state measurement and in vitro release. Pharmacokinetic (PK) studies were conducted in rats and dogs, comparing the formulations with different particle sizes by oral and IM administration. 15% VTXP stabilized by 3% poloxamer 338 suspensions exhibited optimal injection properties: suitable viscosity (10-13cP) and moderate injection force (8-24 N). All VTXP suspensions had similar overall release profiles, minor differences were observed in their drug release behavior within the first 2 h. 2.5 µm VTXP suspension had extended t_1/2 (rat 188 h, dog 39.6 h) by intramuscular (IM) administration, compared to t1/2 (rat 2.8 h, dog 8.3 h) via intragastric Route (IG) administration. Additionally, lower burst releases were confirmed (rat 10.2%, dog 3.8%) by the animal test. This study confirms that the VTXP suspension achieves long-acting performance and low burst release for IM administration.