Development cycle

Preformulation study

• API characterization: Optical microscopy, assays, DRX, PSD, Log P, Log D, membrane permeability…

• Compatibility study

• Solubility study:

o Solubility at saturation in different media

o Solubility improvement: Cyclodextrin complexation, co-solvent, surfactants, micronization…

o Modelization (software)

o Early conservation study

• Preclinical batches manufacturing

Analytical methods development

• API assay

• Impurities assay and forced degradation study

• Preservative and antioxidant assays if necessary

• Sterility and microbiological controls

Formulation study

• Different forms: Solution, Gel, Emulsion, Micellar solution, Micro and nanoemulsion, Nanosuspension

• Formulation development by QBD (risk analysis and DoE on Jmp software)

• Rheology (viscoelastic behavior, gelation assessment, resistance under simulated eye blinking, viscosity behavior after tear contact…)

• Bioadhesion (mucoadhesive force)

• PSD by laser diffraction and DLS, Zeta potential if necessary

• Packaging choice: single or multiple use, glass or plastic

• Finished product characterization: Appearance, pH, Osmolality, Density, Drop size, Viscosity

Sterilization study

• Steam sterilization impact

• Filtration study

• Filterability study

Container/contents interactions

• Stressed studies

• Extractables and leachables (support of packaging supplier)

Scale-up study

• Process robustness evaluation by QBD (risk analysis and DoE on Jmp software)

• Preliminary stability study

• Technical batches

• Analytical methods validation

• Cleaning verification (product cleanability) with LOQ method validation and recovery efficiency

• Clinical batches manufacturing

Industrialization

• Small commercial batches

• Process validation

• Sterilization validation

• ICH stability studies and ongoing stability studies

• ICHQ3D and nitrosamines studies