Comprehensive preformulation is the foundation of robust pharmaceutical formulations
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The preformulation phase is the stage of pharmaceutical development in which an API (Active Pharmaceutical Ingredient) turns into the drug substance.  It is in the preformulation phase that the appropriate solid form and stable polymorph of a drug substance is selected in view of the intended dosage form and delivery route.

 

Many drug substances fail in the preclinical phase.  Although a large portion of compounds will fail due to toxicity reasons, 15% fail for lack of bioavailability.  In addition, the strict regulatory requirements for toxicity studies demand an exposure in test animals of close to 100 fold the EC50 value.  For poorly soluble APIs, achieving such exposure levels is a real barrier.  Early preformulation data on solubility and dissolution of various (solid) forms of your API assist in judging the risk of your drug substance in the preclinical studies.  It is possible to improve the solubility and dissolution rate by choosing a specific salt or co-crystal or, indeed, an amorphous dispersion.  Specific enabling (preclinical) formulations are another means of increasing the bioavailability.

 

Preformulation assays are essential for the success of your drug substance in the preclinical phases.  When you base your decisions on a sound data package that takes both bioavailability as well as manufacturability into account you have already mitigated your development risks substantially. 

 

Crystallics has developed a critical set of assays that look at bioavailability and manufacturability related characteristics of your drug substance. These assays guide you through the selection of the appropriate solid form of your API.  Special attention is paid to parameters such as crystallinity, melting point, hygroscopicity, polymorphism, chemical and physical stability both in solid state and in solution under various relevant conditions.  The solubility and (intrinsic) dissolution rate are, of course, also studied.  Automation with liquid handling robots and 96 well plate readers allow Crystallics to perform these experiments in a compound sparing manner.  Techniques such as variable temperature and variable humidity X-ray powder diffraction provide great insights in the mechanisms of solid form transformations and help making the right choice of form.

 

For further information on how Crystallics can support you with preformulation studies please contact Marcel Hoffmann, CSO, on +31 20 820 2690 or This e-mail address is being protected from spambots. You need JavaScript enabled to view it