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
