Application of solid-state 13C relaxation time to prediction of the recrystallization inhibition strength of polymers on amorphous felodipine at low polymer loading

The potential for inhibiting recrystallization with Eudragit(R) L (EUD-L), hypromellose acetate succinate (HPMC-AS), and polyvinylpyrrolidone-co-vinylacetate (PVP-VA) on amorphous felodipine (FLD) at low polymer loading was investigated in this study. The physical stabilities of the FLD/polymer amorphous solid dispersions (ASDs) were investigated through storage at 40 degrees C. The HPMC-AS and PVP-VA strongly inhibited FLD recrystallization, although EUD-L did not effectively inhibit the FLD recrystallization. The rotating frame (1)H spin-lattice relaxation time ((1)H-T1rho) measurement clarified that EUD-L was not well mixed with FLD in the ASD, which resulted in weak inhibition of recrystallization by EUD-L. In contrast, the HPMC-AS and PVP-VA were well mixed with the FLD in the ASDs. Solid-state (13)C spin-lattice relaxation time ((13)C-T1) measurements at 40 degrees C showed that the molecular mobility of the FLD was strongly suppressed when mixed with polymer. The reduction in the molecular mobility of FLD was in the following order, starting with the least impact: FLD/EUD-L ASD, FLD/HPMC-AS ASD, and FLD/PVP-VA ASD. FLD mobility at the storage temperature, evaluated by (13)C-T1, showed a good correlation with the physical stability of the amorphous FLD. The direct investigation of the molecular mobility of amorphous drugs at the storage temperature by solid-state NMR relaxation time measurement can be a useful tool in selecting the most effective crystallization inhibitor at low polymer loading.