Mechanistic insights into the crystallization of coamorphous drug systems

Effects of Polymers on Cocrystal Growth in a Drug–Drug Coamorphous System: Relations between Glass-to-Crystal Growth and Surface-Enhanced Crystal Growth

“…Crystallization of amorphous systems involves molecular rearrangements, which require sufficient energy to overcome the activation energy ( E a ) barrier . As shown in Figure a, the crystal growth kinetics of diffusion-controlled growth, GC growth, and fast surface growth of CBZ-CEL cocrystals followed the Arrhenius equation ln nobreak0em0.25em⁡ u = ln nobreak0em0.25em⁡ A − E normala RT where u is the crystal growth rate, A is the pre-exponential factor, E a is the activation energy required for transporting a molecule from the amorphous phase to the crystalline phase, R is the gas constant, and T is the crystallization temperature.…”

“…The parameters D and T 0 in eqs – are the VTF equation parameters and can be obtained from the fragility m according to eqs – ,, D = 2.303 false( m min false) 2 / ( m − m min ) m min = lg ( τ T g / τ 0 ) ≅ lg ( 100 / 10 − 14 ) = 16 T 0 = T g ( 1 − m min / m ) where τ T g is the relaxation time at T g and m min is the minimum m value, which is approximately equal to 16. Fragility is defined as the temperature change in the relaxation time at T g (eq ), which can be approximated with eq and the apparent activation enthalpy Δ H * m = normald ( lg ⁡ τ ) normald ( T normalg / T ) , T = T g m ≅ <...…”

“…The parameters D and T 0 in eqs – are the VTF equation parameters and can be obtained from the fragility m according to eqs – ,, where τ T g is the relaxation time at T g and m min is the minimum m value, which is approximately equal to 16. Fragility is defined as the temperature change in the relaxation time at T g (eq ), which can be approximated with eq and the apparent activation enthalpy Δ H * where R is the gas constant.…”

“…Crystallization of amorphous systems involves molecular rearrangements, which require sufficient energy to overcome the activation energy (E a ) barrier. 39 As shown in Figure 10a, the crystal growth kinetics of diffusion-controlled growth, GC growth, and fast surface growth of CBZ-CEL cocrystals followed the Arrhenius equation 59 where u is the crystal growth rate, A is the pre-exponential factor, E a is the activation energy required for transporting a molecule from the amorphous phase to the crystalline phase, R is the gas constant, and T is the crystallization temperature. As presented in Figure 10a for CBZ-CEL cocrystals, the calculated activation energy E a for GC growth was 75 ± 10 kJ/mol, which was evidently smaller than the value for the diffusioncontrolled mode (240 ± 6 kJ/mol).…”

“…The parameters D and T 0 in eqs 1−2 are the VTF equation parameters and can be obtained from the fragility m according to eqs 3−5 35,38,39…”