Influence of polymer addition on the amorphization, dissolution and physical stability of co-amorphous systems

Co-amorphous systems have been developed to address the solubility challenge of poorly-water soluble drugs. However, the dissolution rate of co-amorphous systems can be too fast in some cases, causing super-saturation, followed by precipitation and thereafter loss of the advantage. In this study, hydroxypropyl methylcellulose (HPMC) was co-formulated at 10% (w/w) with carvedilol-L-aspartic acid (CAR-ASP) co-amorphous systems at CAR to ASP molar ratios of 1:1, 1:1.5 and 1:2. No obvious changes of glass transition temperatures (T_gs) were detected for CAR-ASP 1:1.5-HPMC and CAR-ASP 1:2-HPMC compared to the corresponding co-amorphous systems, whilst CAR-ASP 1:1-HPMC showed an increased T_g (88.9 ± 1.3 °C) compared to CAR-ASP 1:1 (80.2 ± 0.9 °C). HPMC was involved in the molecular interactions of the CAR-ASP-HPMC systems, but did not disturb ionic interactions between CAR and ASP. Addition of HPMC optimized the dissolution of the CAR-ASP systems by reducing the initial dissolution rate and maintaining super-saturation for a longer period. No negative effect of HPMC addition on physical stability was observed at 25 °C and 40 °C under dry conditions for 7 months. Therefore, it appears promising to co-formulate a small amount of polymer with co-amorphous systems to achieve optimized dissolution characteristics while maintaining the desired physical stability.