In vitro and in vivo evaluation of albumin-encapsulated primaquine diphosphate prepared by nebulization into heated oil.

ABSTRACT

Nebulization of an aqueous mixture of primaquine diphosphate and albumin into heated vegetable oil produces spherical particles with an average size of 6 microm. The microparticles are relatively stabile in buffers of pH 7.2 and 4.5 and completely degrade when exposed to proteolytic enzymes such as trypsin. Pharmacokinetic evaluation of the albumin-encapsulated primaquine diphosphate shows significantly higher levels in mouse liver tissue relative to free drug 2-48 h post-IP administration. Higher AUC (2.8x), lower steady-state volume of distribution (10x) and slower half-life (2.5x) relative to an equivalent dose of free primaquine diphosphate suggest liver targeting and sustained release of the drug from the microparticles.