Crystal Growth Kinetics of a Metastable Polymorph of Tolbutamide in Organic Solvents

Abstract

The crystal growth of tolbutamide (Form IL) in different solvents has been investigated by isothermal seeded desupersaturation experiments at different temperatures (268–283 K). Experimental data have been evaluated using empirical power law equations and the mechanistic based models: Burton–Cabrera–Frank (BCF) and birth and spread (B + S). The estimated activation energies and growth exponents suggest surface integration controlled growth as confirmed separately by mass transfer analysis. From the B + S model, the estimated solid–liquid interfacial energies and the mean diffusion distances on the surface range are 1.23–1.90 mJ/m2 and 1–16 nm, respectively. The growth rate is strongly dependent on the solvent, decreasing in the order: acetonitrile > ethanol > ethyl acetate > n-propanol > toluene. The crystal growth becomes slower as the overall strength of the solute–solvent binding increases. This influence of the solvent corresponds very well with that found for nucleation of tolbutamide in the same solvents and further supports the hypothesis that desolvation is an important step in crystallization. The similarity in the influence of the solvent on the kinetics of nucleation and growth very strongly supports the hypothesis that the solvent–solute interactions play an important role in the kinetics of formation of crystalline phases.

Crystal Growth Kinetics of Benzoic Acid in Aqueous Ethanol Solution

“…The growth rate constant k g at each of the solvent compositions is of the order of 10 –7 –10 –6 m/s, and the growth exponent g changes between 1.16 and 1.79 (as shown in Table ), which are comparable with the growth parameters reported in the literature such as 10 –7 –10 –6 and 1.35–1.40 for Piracetam, 10 –6 –10 –5 and 1.09–1.61 for salicylic acid, 10 –7 –10 –5 and 1.12–1.40 for salicylamide, 10 –7 –10 –5 and 1.83–1.87 for ampicillin, and 10 –7 –10 –4 and 0.74–1.47 for tolbutamide …”

“…The growth rate constant k g at each of the solvent compositions is of the order of 10 −7 −10 −6 m/s, and the growth exponent g changes between 1.16 and 1.79 (as shown in Table 4), which are comparable with the growth parameters reported in the literature such as 10 −7 −10 −6 and 1.35−1.40 for Piracetam, 43 10 −6 −10 −5 and 1.09−1.61 for salicylic acid, 44 10 −7 −10 −5 and 1.12−1.40 for salicylamide, 45 10 −7 −10 −5 and 1.83−1.87 for ampicillin, 46 and 10 −7 −10 −4 and 0.74−1.47 for tolbutamide. 47 Based on the previous findings, the effect of solvent composition on growth rate is quite significant, which is furthermore investigated by defining the growth rate constant and exponent as a function of antisolvent mass fraction 19 k k kw k w log( ) where k 0 , k 1 , and k 2 are the parameters for growth rate constant, g 0 and g 1 are the parameters for the exponent part of growth rate, and w w is the water composition in the solvent mixture.…”

Crystal Growth, Dissolution, and Agglomeration Kinetics of Sodium Chlorate

“…In such cases, the overall molar flux to the growing crystals R g (mol m –2 s –1 ) can be expressed as a simple function of the dimensionless thermodynamic driving force σ, if it is assumed that the concentration at the interface is approximately equal to the bulk solution concentration, as , where k d is the mass-transfer coefficient (mol m –2 s –1 ). From eq , the overall linear growth rate under diffusion control G diff (m s –1 ) can be estimated as ,, where k a and k v are the surface and volume shape factors (taken here as k a = 6 and k v = 1 for the cubic sodium chlorate crystals), ρ c is the crystal density (taken as 2500 kg m –3 for sodium chlorate), and M is the molecular weight (106.44 g mol –1 for sodium chlorate). The unknown parameters k d or directly k d ′ (m s –1 ) can be estimated based on empirical correlations, taking into account the fluid dynamics of the stirred crystallizer or by dissolution experiments, if it can be proved (or assumed) that the dissolution process is purely diffusion controlled.…”

“…where k d is the mass-transfer coefficient (mol m −2 s −1 ). From eq 16, the overall linear growth rate under diffusion control G diff (m s −1 ) can be estimated as 39,42,43…”

Parameter Estimation of the Stochastic Primary Nucleation Kinetics by Stochastic Integrals Using Focused-Beam Reflectance Measurements

“…In this study, the kinetic parameters were defined by Equation ( 31) and the parameters of the distribution by Equation (30). These parameters can be changed, removed, or added.…”