Modern Pharmaceutics

Dissolution Behavior of Weakly Basic Pharmaceuticals from Amorphous Dispersions Stabilized by a Poly(dimethylaminoethyl Methacrylate) Copolymer

“…However, a number of compound classes challenge the current workflows to design and generate amorphous solid dispersions (ASDs). , Weakly basic pharmaceuticals are one such example . Weak bases (as well as neutral compounds) can leech from ASDs in gastric conditions at rates that exceed the dissolution of stabilizing excipients, such as the commonly employed acidic stabilizer hydroxypropyl methylcellulose acetate succinate (HPMCAS), which can result in precipitation and in vivo exposure sensitive to pH. − Although methods have been devised to mitigate high concentrations of API at low pH by dosing large particle size amorphous dispersions, , the same strategies that slow dissolution can negatively impact bioperformance . Additionally, strong hydrogen bonding between drug and polymer can reduce the maximum achievable drug concentration during dissolution. , An alternative strategy is to disperse API in readily water-soluble carriers, such as poly­(vinyl pyrrolidone- co -vinyl acetate), which ensures the presence of dissolved polymer in gastric conditions .…”