A comparison of a DSC and a wet granulation simulated API-excipient mixtures analyzed by HPLC.

What is it about?

This work was initiated/intended to validate the many published articles promoting the simpler DSC methodology because the methodology was presented in several publications but never validated. We intended to show that a wet granulation simulation followed by rate accelerating temperature storage for a short period produced the same predictions regarding compatibility and incompatibility of API-excipient mixtures. The DSC method was so simple. Run a DSC of the API, the excipient, and the combination. Compare the heats of melting, and the mixtures with the greatest % difference of API vs API-excipient are predicted to be the most likely to be incompatibility. The DSC method took 8 hours to complete, about 10 min per DSC, sufficient time to compare 8 combinations. The WG simulation and isothermal-stress method required the work of one analyst for 4 full days, preparation, overnight drying, and HPLC analysis overnight. The results were a surprise. The DSC method and the WG-isothermal-stress methods' predictions were in complete opposition. The WG-isothermal-stress method mixtures were also stored at ambient temperature for 2 years, after which the HPLC analysis was repeated. The isothermal stress method's results from 1 and months were exacting predictive of the st abilities at ambient temperature. The DSC method was not verified or validated; however, the WG-isothermal-stress methodology was verified as an accurate predictor of incompatibilities and incompatibilities.

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Why is it important?

Preformulation studies are designed to provide information and data to support development of pharmaceuticals. Inaccurate predictions waste resources. Particularly time, effort, drug substance and rug product.

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