Multicomponent solid dispersion as a formulation strategy to improve drug permeation: A case study on the anti-colorectal cancer irinotecan

Abstract

Multicomponent solid dispersions (MSD)s are frequently proposed as efficient drug delivery systems to improvedrug solubility and bioavailability. In this study, the effects of specific excipients, such as mannitol, inulin, poly(methyl methacrylate-co-methacrylic)acid (PMMA) and cellulose acetate phthalate (CAP) have been tested topotentially improve irinotecan (IRN) permeation in the intestinal tract with the intention to protect the drugfrom the gastric environment. MSDs were formulated as microparticles by Spray-Drying technique. Raw ma-terials and microparticles have been characterized by FTIR analysis to determine hydrogen bonding. SEM imageswere recorded to investigate morphology and particle size of drug-loaded microparticles, and thermal analysiswas used to confirm that drug physical morphology was maintained during formulation. Finally, in vitro dis-solution studies andex-vivoexperiments across colon sections were carried out. The drug-loaded microparticlesresulted to have an average particle size of below 6μm and increased both drug dissolution rate and permeationthrough the intestine. The use of specific excipients improved properties such as drug dissolution performancesand drug absorption through the intestinal barrier. The selected method and excipients increased IRN dissolutionrate in all the formulations prepared. Finally,ex-vivoexperiments across colon sections demonstrated an increaseof drug permeation through MSDs respect pure IRN.