Drug release pattern of oral dual-release pellets through the gastrointestinal tract: Case example of diclofenac sodium

Abstract

The purpose of this research was to evaluate the release pattern of the dual-release pellets of diclofenac sodium (DS), coated with enteric-and sustained-release layers, in dissolution media that resemble the physiological variables of the gastrointestinal (GI) fluid. Dissolution testing in three pH stages (acidic, intermediate, and basic) was conducted using USP apparatus I (basket) rotating at 100 rpm. The acidic pH stage resembles the gastric fluid during fasted and fed states, the intermediate pH stage resembles the fluid of the proximal small intestine (duodenal fluid), and the basic pH stage resembles the fluid of the small intestine during fasted and fed states and distal GI. DS pellets showed excellent gastric resistance in the acidic pH stage for 2 h. In the intermediate pH stage, DS pellets showed a gastric resistance for 2 h, followed by a low percent of DS release thereafter (15.2% after 10 h). DS release was accelerated in the basic pH stage, particularly in pH media 6.5–7.2. This is because the enteric-coated film starts to dissolve at pH > 5.5. In addition, DS release was influenced by the buffer capacity (β)/ionic strength (I) of the dissolution media, where DS release increased with increasing β/I of phosphate buffers (pH 6.8) up to a concentration of 50 mM and then decreased at 100 mM. These dissolution results corroborated with equilibrium solubility data and sink conditions (S values) of DS in the media of the three pH stages. This study provides an insight into the release pattern of the dual-release DS pellets throughout the GI tract to better correlate the in vitro release data of these pellets to those in vivo.