Wednesday, July 29, 2015

Kinetics from HPLC data - DynoChem guidance documents

HPLC area and area percent are some of the most commonly used data for reaction and impurity profiling and monitoring.  Customers collect these data all the time, whether working in the lab or the plant, in early or late phase development.  HPLC data are routinely used in regulatory filings and to ensure quality and compliance.

The good news for DynoChem users is that reaction kinetics may also be obtained from these data, when certain conditions are met.  Yes, there is some fine print, but not too much.  Armed with kinetics, you can run fewer, better experiments and save weeks or months of experiments and speculation.  (You might enjoy our playlist of short humorous videos on this very topic.)

In this and several other application areas, our team have recently written new 'Guidance Documents'. These follow a standard format and are short and to the point.  They provide a helicopter view and a roadmap for applying DynoChem in a specific application area.  Naturally the guidance document for reaction kinetics puts a lot of emphasis on HPLC data.  You can get the full story by following this link.

Contents page of the Reaction Modeling Guidance Document: click for step by step instructions.

Wednesday, July 8, 2015

Generate cocrystal ternary phase diagrams to support process design

We love to provide solutions that save customers time.  A good example arises in process and experimental design aimed at formation of cocrystals.

DynoChem already includes tools to support solvent selection for crystallization and these can indicate the effects of solvent choice on API ("A"), coformer ("B") and cocrystal ("AB") solubility, based on a handful of measurements in a few solvents.  We also provide templates for solution-mediated conversion between forms and drug product salt disproportionation in the presence of excipients.

For cocrystals, once solubilities are known, either by measurement or prediction, a DynoChem dynamic model can simulate in a few seconds the time-dependent equilibration of a large set of potential experiments, reducing the need for painstaking and slow lab experimentation.

Figure 1: Process scheme for simulating cocrystallization process; more solid phases may be included as needed

With this model, users can simulate the relative and total amounts of each of the (e.g. three) solid phases that may result from different starting conditions.  Those results can be plotted and summarized on a ternary phase diagram that summarizes the 'regions' of initial composition that lead selectively to formation of the desired phase.

Figure 2: Ternary phase diagram for an example cocrystal system, with a 1:1 cocrystal AB.

Contact if you'd like to discuss using these tools, or related applications to enantiomers and other systems.  Thanks to Dr Andrew Bird for providing the above illustrations.  

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