Pre-Formulation ResearchPre-formulation characterization studies generally include accelerated stability (stress) studies, stability-indicating analytical method development, and other physiochemical characterizations designed to pinpoint potential product candidate stability problems and enable formulation optimization.
- Understand the significant physicochemical properties
- Estimate a product’s stability when exposed to various common stresses
- Develop stability-indicating assays for major degradation products
- Decide upon a lyophilized or liquid formulation for initial clinical studies
- Finalize a formulation development research protocol (matrix of buffer, pH, stabilizer, tonicity modifier; analytical methods; etc.)
Sufficient stability information is required to achieve liquid formulations as most biopharmaceuticals have limited stability in liquid state. It is also important to understand that product stability in prefilled syringe may be different from the same formulation filled in vials.
- Efficient lyophilization cycle
- Elegant appearance of the lyophilized cake
- Good stability during the freeze-drying process.
- Easy, rapid, and thorough reconstitution
Appropriate for clients wanting to quickly determine if their compound is safe and effective in early (Phase I) clinical trials.
Combining two products in one formulation, e.g., co-formulation, is used when multi-dosing from a single vial is beneficial. In general, the addition of preservative(s), regardless of the type and amount utilized, significantly changes the stability profiles of proteins. In some extreme cases, visible precipitation and aggregation have been reported from the introduction of these materials. Therefore, the effect of various preservatives on the stability of protein should be carefully examined. Other experiments are also required to qualify a protein product for multi-dose formulation capabilities. The most notable tests include analyses for antimicrobial preservative effectiveness and stopper resealing. As proteins have limited stability in the presence of preservatives, dual chamber syringes or dual chamber cartridges containing bacteriostatic diluents are routinely used.