Shital Mehta's presentation on preformulation strategies in drug development provided a comprehensive overview of the critical role of preformulation in the early discovery phase. Mehta began by highlighting the importance of understanding the physical and chemical properties of drug candidates to design formulations that are fit for purpose. This involved considering factors such as dose, route of administration, and chemical scaffold.
Mehta emphasised that solubility was a crucial parameter in drug development, particularly for modern, more lipophilic compounds. Different types of solubility, including kinetic, equilibrium, and apparent solubility, were discussed, along with their relevance at various stages of drug development. The balance between solubility and potency, as well as the consideration of bio-relevant media for solubility and food effect predictions, were also highlighted.
Collaboration across disciplines was underscored as essential for aligning formulation strategies with study goals and target product profiles. Mehta stressed the need for open and close collaboration with medicinal chemistry, pharmacology, toxicology, and CMC groups to ensure that formulations were optimised for pharmacokinetic (PK), pharmacology (PD), and toxicology studies.
The presentation detailed the formulation support required for various early-stage studies, including PK, PD, and GLP tox studies. Mehta discussed the use of cosolvents, surfactants, and other excipients, as well as the need for fresh formulations to avoid stability issues. The importance of understanding species-specific excipient tolerability and the potential use of cassette dosing to increase throughput was also covered.
Finally, Mehta provided decision trees for formulation development, emphasising the need to consider the chemical scaffold’s properties, route of administration, study duration, and endpoints. The transition from animal to first-in-human formulations was discussed, along with the importance of understanding the maximum absorbable dose (MAD) and the need for enhanced formulations for poorly soluble compounds.
In conclusion, Mehta's presentation highlighted the critical role of preformulation in drug development, the importance of solubility, the need for cross-disciplinary collaboration, and the detailed formulation support required for early-stage studies. The decision-making process for formulation development and the transition to clinical formulations were also emphasised as key components of successful drug development.
