Applications of In Silico Solvent Screening and an Interactive Web-Based Portal for Pharmaceutical Crystallization Process Development.

In an effort to reduce development time and costs associated with active pharmaceutical ingredient process solvent selection and crystallization design, a tiered approach to crystallization solvent selection was developed that leverages different solubility modeling tools selected on the basis of available data and the intended use of the prediction. To facilitate easy access to routine solubility modeling functionality with a high level of automation and parallelization, a web-based in silico solvent-screening tool was also developed as well as a user interface to visualize and interpret the large number of predicted results. Examples are presented to illustrate the utility of the workflow and solvent-screening tool at various stages of development for a diverse range of crystallization processes.

Particle engineering: a strategy for establishing drug substance physical property specifications during small molecule development.

A strategy for physical property control of a drug substance has been developed that utilizes a science-based approach to define key drivers for particle control. These drivers are based on in vivo performance (or expected performance), content uniformity of the drug substance in drug product, and manufacturability of drug product. Quality by design principles have been used in developing the strategy.

Physics of amorphous solids.

The physical state of a dosage form, crystalline versus amorphous, is critical in determining its solid-state physical and chemical properties. This minireview describes the physics associated with the preparation and storage of amorphous solids including a review of the common theories of the glass transition and relaxation processes.

Prediction of the relaxation behavior of amorphous pharmaceutical compounds. I. Master curves concept and practice.

Variability in the time to crystallization is a major technical and economic hurdle in using amorphous solids in dosage forms. It is hypothesized that amorphous solids "age", and that the older they are, the more relaxed they are and the higher the probability of crystallization. At present, there is no method that allows the "effective age" of an amorphous raw material to be assessed relative to its unrelaxed initial condition.