Introduction

Preclinical formulation development plays a crucial role in pharmaceutical research, laying the foundation for successful drug discovery and clinical progression. Getting the formulation right early helps mitigate development risks and avoids costly reformulation in later stages.

The key factor for formulation success at this early stage is the solubility of a new chemical entity (NCE) in a formulation vehicle—without solubility, further development becomes unfeasible. A data-driven approach incorporating miniaturization is thus essential to ensure success.

Solubility: The Critical Barrier in Preclinical Formulation

Most NCEs exhibit poor aqueous solubility falling into the Biopharmaceutics Classification System (BCS) Classes II and IV. For these compounds, solubility is the critical go/no-go factor in determining preclinical success—if the drug cannot be solubilized effectively, it cannot be delivered in a viable formulation. The key question for successful pharmacological, pharmacokinetic, and safety outcomes, then, is identifying a formulation strategy that enhances the bioavailability of these NCEs.

Preclinical scientist face an additional hurdle: limited quantities of drug material, which restrict the comprehensive formulation testing needed to make informed decisions.

Preclinical Formulation Challenges

Solubility and dissolution rate enhancing formulation strategies—such as particle size reduction, pH adjustment, surfactants, complexation agents, organic solvents, solid dispersions, and lipid-based vehicles—are available for most NCEs. The challenge lies in the material constraints that limit the insights that can be achieved by traditional gram-scale testing. The real question is not whether a drug can be delivered effectively, but how to select the optimal strategy when only limited information is available.

Bridging Challenges with Innovative Solutions

To address this, The Solubility Company has created the Alpha Formulation™ screen —the industry’s earliest formulation screen—to rapidly identify optimal vehicles for preclinical drug dosing, often using as little as a single milligram of an NCE.

By miniaturized screening of particle level solubility and dissolution across relevant media—aqueous buffers, biorelevant media, solvents, complexation agents, surfactants, lipids, and more—drug developers gain comprehensive understanding of a molecule’s behavior. By prioritizing formulation strategies based on solubility, the Alpha Formulation™ screen gives visibility, eliminating non-viable options early and preventing costly late-stage failures and reformulation needs.

Make confident formulation decisions from the outset for a de-risked path to IND submission – talk to our experts.

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