Generality of Enhancing the Dissolution Rates of Free Acid Amorphous Solid Dispersions by the Incorporation of Sodium...

The incorporation of a counterion into an amorphous solid dispersion (ASD) has been proven to be an attractive strategy to improve the drug dissolution rate. In this work, the generality of enhancing the dissolution rates of free acid ASDs by incorporating sodium hydroxide (NaOH) was studied by surface-area-normalized dissolution. A set of diverse drug molecules, two common polymer carriers (copovidone or PVPVA and hydroxypropyl methylcellulose acetate succinate or HPMCAS), and two sample preparation methods (rotary evaporation and spray drying) were investigated. When PVPVA was used as the polymer carrier for the drugs in this study, enhancements of dissolution rates from 7 to 78 times were observed by the incorporation of NaOH into the ASDs at a 1:1 molar ratio with respect to the drug. The drugs having lower amorphous solubilities showed greater enhancement ratios, providing a promising path to improve the drug release performance from their ASDs. Samples generated by rotary evaporation and spray drying demonstrated comparable dissolution rates and enhancements when NaOH was added, establishing a theoretical foundation to bridge the ASD dissolution performance for samples prepared by different solvent-removal processes. In the comparison of polymer carriers, when HPMCAS was applied in the selected system (indomethacin ASD), a dissolution rate enhancement of 2.7 times by the incorporated NaOH was observed, significantly lower than the enhancement of 53 times from the PVPVA-based ASD. This was attributed to the combination of a lower dissolution rate of HPMCAS and the competition for NaOH between IMC and HPMCAS. By studying the generality of enhancing ASD dissolution rates by the incorporation of counterions, this study provides valuable insights into further improving drug release from ASD formulations of poorly water-soluble drugs.