Carvedilol microemulsion-loaded oleogel for oral delivery: investigation of <i>in vitro</i> drug release and evaluation of chemical and physical stability

A semisolid oral formulation of carvedilol microemulsion-loaded oleogel (CARV-MEOG), filled in hard gelatin capsules, was developed and investigated for <i>in vitro</i> dissolution at different physiological pH levels. <i>In vitro</i> dissolution studies were conducted on CARV-MEOG and the reference product, Coreg^® CR, in dissolution media that simulate the gastrointestinal fluid and cover its physiological pH range. The stability of CARV-MEOG was assessed both chemically and physically. Results showed that CARV formed intermolecular forces with oleic acid, the oil phase of the microemulsion, through the N-H bond of CARV, which disappeared in the CARV and oleic acid mixture. In 0.1 M HCl dissolution medium, CARV release attained 102.5 ± 2.66% after 24 h. In pH 4.5, 6.8, and 7.5 dissolution media, CARV release was significantly lower, achieving 65.6 ± 2.73%, 20.1 ± 1.32%, and 26.3 ± 1.67%, respectively, after 24 h. Compared to Coreg^® CR, the release of CARV after 24 h was lower than that from CARV-MEOG, attaining 91.2 ± 1.03%, comparable to CARV-MEOG in pH 4.5, where it reached 76.8 ± 1.32%, and it was higher than CARV-MEOG in pH 6.8 and 7.5, attaining 59.0 ± 0.88% and 54.2 ± 1.01%, respectively. CARV-MEOG remained stable for 6 months when stored at 5-8 °C. Therefore, the development of CARV-MEOG successfully enhanced the dissolution rate of the poorly soluble drug carvedilol, aiming to improve its oral bioavailability.