Skip to content
HOME arrow Preformulation Study Contract Formulation Research


Home > Contract Research > Formulation Development > Preformulation Study

Preformulation studies generally include accelerated stability (stress) studies, stability-indicating analytical method development, and other physiochemical characterizations designed to pinpoint potential protein/peptide stability problems and enable formulation opimization. The following table shows examples of preformulation studies.

Characterizations
Examples
Stress Studies Accelerated stability studies Heat, Freezing, pH, Light, Agitation, Oxidation, Dehydration, Surfaces, Shear, etc.
Key Degradation products Aggregation, Oxidation, Deamidation, Cleavage, Surface adsorption, surface denaturation, etc.
Stability-indicating assays HPLC, Electrophoresis, Spectrometry, particle count, turbidity, etc.
Physical characterizations Primary, secondary, tertiary, and quaternary structures, thermal denaturation temperature, solubility, viscosity, molecular weight, extinction coefficient, etc.
Biological Characterizations Substrate or receptor affinity, in vitro bioassay (information typically provided by customers)

The objectives of the pre-formulation research will include:

  • Understanding the pharmaceutically significant physicochemical properties
  • Estimating product's stability when exposed to various common stresses
  • Developing stability-indicating assays
  • Deciding upon a lyophilized or liquid formulation for initial clinical studies
  • Finalizing a formulation development research protocol (matrix of buffer, pH, stabilizer, tonicity modifier; analytical methods; etc.)

Example of Integrity Biosolution's preformulation study Package (2-3 months)

A preformulation study will perform systematic research designed to examine the physicochemical properties of protein/peptide that may be important in formulation development. During such a study, the protein/peptide will be exposed to various stresses, key degradation products will be identified, and appropriate stability-indicating assays will be developed. The protein/peptide products will be exposed to the following stresses:

  • Elevated temperatures, e.g., 37 and 45 degree C
  • pH's between 3.0 and 8.0
  • Ultraviolet and fluorescent light
  • Agitation and shear
  • Oxidation
  • Freeze-thawing

From this, the following stress-induced changes will be investigated:

  • Aggregation and/or precipitation
  • Deamidation or cyclic imide formation (if relevant amino acid residues are present in the sequence)
  • Oxidation (if relevant amino acid residues are present in the sequence)
  • Recovery

The following analytical methods will be used to determine the degradation products. From amongst these, stability-indicating methods will be identified.

  • Size-exclusion HPLC
  • Reversed-phase HPLC
  • Ion-exchange HPLC
  • Electrophoresis
  • Turbidity assay
  • Protein concentration assay

Protein/peptide requirement = 500 x estimated therapeutically effective concentration

Structure-stability relationship study (1-2 months in parallel with the Preformulation Studies)

The structural changes of proteins/peptides at various pH's and temperatures (5-60 degree C) will be examined with Circular Dichroism, Fluorescence (intrinsic and hydrophobic probe binding), UV, FTIR, and/or differential scanning calorimetry. If any significant changes are discovered, the structure-stability relationship will be examined by carrying out a short-term stability study.

Protein/peptide requirement = 10 x estimated therapeutically effective concentration.

 
Site Managed By: Computer Repair Thousand Oaks