Effect of Mannitol on Nucleation and Crystal Growth of Amorphous Flavonoids: Implications on the Formation of Nanocrystalline Solid Dispersion

In this work, we studied crystallization kinetics of amorphous hesperetin (HRN) and naringenin (NRN) alone, and in 1:1 proportion with mannitol at Tg + 15 K. Crystallization rate of NRN was found to be significantly higher than HRN. Mannitol accelerated crystallization of HRN as well as NRN. NRN exhibited higher crystallization rate than HRN, in presence of mannitol, as well. Finke-Watzky model was used to deconvolute the crystallization kinetics data into nucleation and crystal growth rate constant. HRN alone had 9.56 × 109 times faster nucleation rate and 1.88 times slower crystal growth than NRN alone. Mannitol increased nucleation and crystal growth rate of HRN as well as NRN. In presence of mannitol, HRN possessed 1.34 × 1010 times faster nucleation rate and 1.70 times slower crystal growth rate than NRN. Differences in crystallization behavior of HRN and NRN were explained by their thermodynamic properties. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3789-3797, 2015