With physicochemical data derived from preformulation studies, the formulation scientist can leverage this information to assess initial compatibility of formulation components and begin activities surrounding process design. During this phase of the development, importance is placed on optimization of the formulation development of the final dosage form and process design. Also during this phase, consideration is given to factors affecting scale-up from bench top to pilot scale.
In QbD, this phase is focused on providing a defined design space to meet FDA and ICH guidelines. Within this area of focus, greater detail is developed for Critical Mat erials Attributes (CMA) and Critical Process Parameters (CPP).
|Particle Size||Bioavailability, Powder Flow, Compaction, Compression, Dissolution, Blend Uniformity, Protein Aggregation||In a final crystallization step, particle size is a CQA (critical quality attribute) used to determine design space variables. Particle size distribution also has a direct impact on biologic material performance and processing. It can also be indicative of undesirable protein aggregation.|
|Particle Shape||Bioavailability, Compaction, Critical Element in Solid and Liquid Dispersion Processing||Product morphology in addition to size has direct influence on solubility. Inhaled products are based on less than 5 µm aerodynamic shape to be deposited in the lungs and not upper respiratory areas. Shape can be used as a PAT to define process send points and batch-to-batch variability.|
|Surface Area||Dissolution, Solubility Compaction, Milling, Stability, Lyophilized Products||It is apparent that the dissolution rate of a drug can be proportional to the surface area exposed to the dissolution medium. Surface area can provide critical information in lyophilization in regard to ice crystal formation.|
|Density||Roller Compaction-Lubrication Tableting Setting, Segregation, Compaction, Crystallinity||API and excipients are blended and typically then granulated or densified to ensure a uniform blend is delivered to the tablet press. The material is also granulated to aid in material movement as granulations move easier than powder blends. True density can be indicative of how close the material is to a crystalline state or the proportions of a binary mixture.|
|Porosity||Roller Compaction, Tablet Shelf Life, Fragmentation, Compaction, Content Uniformity/Dissolution||Indicator for shelf life and air and moisture penetration. Porosity measurement can evaluate the ability of liquids to penetrate the tablet for dissolution assessment. Can assist in parameter setting for material flow in coating operations. Predictive evaluation for pellet deformation during compression. Tablet crushing strength influenced by pore size distribution.|
|DVS-Dynamic Vapor Sorption||Stability, Shelf Life, Appearance, Excipient- API Chemical Stability, Cohesion-Adhesion||Loss/formation of water content from API can lead to conversion to amorphous form. Used to evaluate storage/stability and packaging format. Determine effects of moisture induced glass transition and crystallization at specific temperatures. Assess the effect of Protein-Sugar interactions.|
|Inverse Gas Chromatography||Powder Surface Energies, Acid/Base/PolarFunctionality of Surfaces, Diffusion Kinetics, Solubility Parameters, Phase Transition Temperatures|