Fabrication and in vivo evaluation of highly pH-responsive acrylic microparticles for targeted gastrointestinal delivery

Abstract

Acrylic enteric microparticles for oral drug delivery were prepared by an oil-in-oil emulsion solvent evaporation process. The novel use of sorbitan sesquioleate as a surfactant produced Eudragit L55, L and S (pH thresholds of 5.5, 6 and 7, respectively) microparticles of good morphology (spherical, smooth surfaced), size (<100 μm) and size uniformity. The process was efficient (yield approximately 90%) and the encapsulated model drug (prednisolone) was in the amorphous form. The Eudragit L and S microparticles showed excellent pH-responsive drug release in dissolution studies (negligible drug release at pH 1.2; rapid drug release above the polymers' pH thresholds). In contrast, Eudragit L55 particles aggregated in fluid and showed poor control of drug release. In vivo in rats, Eudragit L microparticles released their drug load rapidly (Tmax < 1 h) and the Cmax and AUC were higher than those of a control suspension of prednisolone. Drug absorption from Eudragit S microparticles was low which was attributed to the fact that the threshold pH of Eudragit S was not reached in the rat intestine and drug release was therefore incomplete. It was concluded that although the rat is an inappropriate model for the investigation of Eudragit S microparticles, the positive results seen with the Eudragit L microparticles indicate its potential use in pH-targeted drug delivery.