The importance of formulation screens
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The selection of suitable formulations for the preclinical development stage is an important decision in the development of pharmaceutical products. The wide scope of early animal experiments ranges from proof-of-concept to PK/PD profiling, and from biopharmaceutical evaluation to toxicology assessment. This wide scope leads to challenges in the formulation development, in particular, as different administration routes and doses are required implying a broad range of solution/suspension concentrations.  

 

For example, in an oral administration the molecules of the active pharmaceutical ingredient need to reach the site of absorption and, therefore, dissolution rate and/or solubility are key properties to ensure sufficient oral bioavailability. Many of the drugs developed today have low solubility posing challenges in their development. In addition, diversity in the physiology between various animal species and demands on the route of administration make formulation development even more complicated.

 

The most challenging formulations during the preclinical phase are those aimed at toxicology assessment.  Due to the need of maximizing the exposure to the drug in the toxicology studies, the issue of solubility becomes even more profound and dose linearity is mostly lost at high concentrations for insoluble compounds. Formulations with high-dose suspensions have additional issues such as high viscosity, aggregation and caking.  Furthermore, the selected vehicles should not have any biological activity as it may confound the effects observed.

 

Crystallics has developed a set of formulation screens to identify convenient combinations of vehicles. Solution, suspension or capsule formulations are made possible by selecting appropriate vehicles, taking into account suitability for the intended animal species and administration route.  Once suitable formulations for animal studies are identified, efficacy and safety can be reliably evaluated and the drug can proceed one step further in development.