Polymeric precipitation inhibitor differently affects cocrystal surface and bulk solution phase transformations

During the dissolution of cocrystal particles, solution-mediated phase transformation (SMPT) can occur either on particle surface (PS-SMPT) or in bulk solution (BP-SMPT). In this study, we compared effect various polymers PS-SMPT and BP-SMPT for first time using carbamazepine saccharine (CBZ-SAC) as a model drug. Polyethylene glycol 6000 (PEG), polyvinylpyrrolidone K-30 (PVP), hydroxypropyl methylcellulose (HPMC), acetate succinate (HPMC-AS), amino methacrylate copolymer (EPO), methacrylic acid copolymers (L100-55) were used polymeric precipitation inhibitors. non-sink test, CBZ-SAC rapidly transforms to CBZ dihydrate (CBZ DH) via absence polymers. The enhanced rate subsequent supersaturated concentration order HPMC-AS > HPMC EPO ≫ PVP ≈ L100-55 PEG. On other hand, solvent-shift these inhibited DH different (EPO PEG). affected crystal habit differently between BP-SMPT. Direct observation by real-time polarized light microscopy (RT-PLM) showed that was significantly HPMC-AS, HPMC, EPO, but less PVP, L100-55, Differences solid pH heterogeneous nucleation discussed reason difference inhibitory conclusion, differ For successful development formulation, it is important select potent inhibitor PS-SMPT.