PH Dependence of the Dissolution Rate of EntericCoated Drug Spheres Determined by Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS)

Abstract

Enteric coatings are widely used in formulations of drug delivery spheres. The coating protects an active pharmaceutical ingredient (API) from acidic conditions in the low pH environment of the stomach. The coating breaks down readily at higher pH in the lower intestine to allow absorption of the API. The thickness of the enteric coating is one of the factors that determine the release rate of the drug in the gastrointestinal tract. It is difficult to determine the loading of the drug layer and enteric coating on the core support sphere without conventional dissolution testing during and post manufacture. Broadband acoustic resonance dissolution spectroscopy (BARDS) potentially offers a new, rapid approach to characterizing enteric coatings during their manufacture. BARDS applications are based on reproducible changes in the compressibility of a solvent during dissolution, which is monitored acoustically via associated changes in the frequency of induced acoustic resonances. Two drug sphere formulations that yield characteristic and reproducible data were investigated. A steady-state acoustic lag time is associated with the disintegration of the enteric coating and drug layer in basic solution. This lag time is pH dependent and is indicative of the rate at which the coating and layers dissolve. BARDS analysis has the potential to characterize drug sphere formulations at-line in very short timescales. BARDS represents a complementary technique to conventional dissolution testing that could be used in precompliance testing for quality assurance during manufacture. BARDS data, in the future, may also be indicative of the likely performance of a formulation under USP dissolution testing.