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