Crystal Growth Kinetics of Pharmaceutical Compounds

Abstract

The crystal growth kinetics of piracetam, fenofibrate, phenylbutazone, acetaminophen, carbamazepine, and risperidone in methanol have been studied by two different methods; the isothermal seeded desupersaturation experiment (ISD) and the rotating disk technique (RD). Data has been collected in the range of temperature 288−303 K and at different supersaturations for the ISD experiments. The RD experiments were performed at constant supersaturation. In the ISD experiments, principal component analysis has been used to relate solution concentrations from IR measurements. An empirical power law equation has been fitted to the experimental desupersaturation data, and parameter values suggest surface integration control for all the APIs studied, a conclusion further supported by a separate mass transfer analysis. The order of rate of growth among the compounds and the magnitude of the growth rates determined by the two methods are in good agreement. In addition, the Burton Cabrera Frank (BCF) and Birth and Spread (B+S) surface integration models have been fitted to the ISD desupersaturation data, and average solid−liquid interfacial energies, mean diffusion distances, and surface mass transport rates have been estimated. An analysis of the experimental results and the growth rate parameters is performed to examine to what extent the difference in growth rate of different compounds can be rationalized.

On Comparing Crystal Growth Rates: Para Substituted Carboxylic Acids

“…The question of how to compare linear growth rates of different material/solvent combinations to investigate potential molecular level correlations, as in this current paper (see also for example ref , Figure 11), is not as straightforward as it may seem . Bennema’s reformulation of the BCF equations , to treat solution growth is instructive, clearly demonstrating the dependency of the rate on both solubility and molecular size.…”

“…This higher level of organization and the small energy benefit in this arrangement may be the cause of the longer nucleation times for BA. Incidentally, p BOBA also shows “herring-bones” (Figure c,d), but these arise from “edge···face” approaches between aromatic rings (“Symthon II” in ref ) which are much stronger than the edge···edge approaches between stacks in BA.…”

Crystal Growth Cell Incorporating Automated Image Analysis Enabling Measurement of Facet Specific Crystal Growth Rates

“…The rotating disc technique in which crystals are affixed to a rotating disc submerged in a supersaturated solution , can also offer well-defined hydrodynamic conditions and indeed may be extended to measurement of the growth of single facets . Its drawbacks consist of having to affix crystals to the rotating disk, which may introduce undesired effects on crystal growth, and the effort in sample preparation that goes with this technique.…”

Solubility Measurement of the Crystal Form 1 and Form 4 Nirmatrelvir in Six Mono-Solvents and Two Binary Solvent Mixtures

“…However, the crystallization process development should consider both thermodynamic and kinetic factors. 25,26 In order to accelerate the crystallization speed, a lower system temperature with higher supersaturation as the crystal growth driving force should be necessary. But as shown in the crystal form stability research, crystal form 4 should be stable at the final temperature of 283.15 K. The transformation rate generally increased as the solubility in the host solvent increased.…”