What is the analytical tool that defines a combination of inputs that yields the same output?

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Typical Input Material Attributes, Process Parameters, and Quality Attributes of Pharmaceutical Unit Operations

Pharmaceutical unit operation
Input material attributes	Process parameters	Quality attributes
Blending/mixing
• Particle size • Particle size distribution • Fines/oversize • Particle shape • Bulk/tapped/true density • Cohesive/adhesive properties • Electrostatic properties • Moisture content	• Type and geometry of mixer • Mixer load level • Order of addition • Number of revolutions (time and speed) • Agitating bar (on/off pattern) • Discharge method • Holding time • Environment temperature and RH	• Blend uniformity• Potency• Particle size• Particle size distribution• Bulk/tapped/true density• Moisture content• Flow properties• Cohesive/adhesive properties• Powder segregation • Electrostatic properties
Size reduction/comminution
• Particle/granule size • Particle/granule size distribution • Fines • Particle/granule shape • Bulk/tapped/true density • Adhesive properties • Electrostatic properties • Hardness/plasticity • Viscoelasticity • Brittleness • Elasticity • Solid form/polymorph • Moisture content • Granule porosity/density	Ribbon milling • Ribbon dimensions • Ribbon density • Ribbon porosity/solid fraction
Impact/cutting/screening mills • Mill type • Speed • Blade configuration, type, orientation • Screen size and type • Feeding rateFluid energy mill • Number of grinding nozzles • Feed rate • Nozzle pressure • ClassifierGranule/ribbon milling • Mill type • Speed • Blade configuration, type, orientation • Screen size and type • Feeding rate	• Particle/granule size• Particle/granule size distribution• Particle/granule shape • Particle/granule shape factor (e.g., aspect ratio) • Particle/granule density/Porosity• Bulk/tapped/true density• Flow properties• API polymorphic form• API crystalline morphology• Cohesive/adhesive properties• Electrostatic properties• Hardness/Plasticity• Viscoelasticity• Brittleness • Elasticity
Wet granulation
• Particle size distribution • Fines/Oversize • Particle shape • Bulk/tapped/true density • Cohesive/adhesive properties • Electrostatic properties • Hardness/plasticity • Viscoelasticity • Brittleness • Elasticity • Solid form/polymorph • Moisture content	High/low shear granulation • Type of granulator (High/low shear, top/bottom drive) • Fill level • Pregranulation mix time • Granulating liquid or solvent quantity • Impeller speed, tip speed, configuration, location, power consumption/torque • Chopper speed, configuration, location, power consumption • Spray nozzle type and location • Method of binder excipient addition (dry/wet) • Method of granulating liquid addition (spray or pump) • granulating liquid temperature • granulating liquid addition rate and time • Wet massing time (post-granulation mix time) • Bowl temperature(jacket temperature) • Product temperature • Post mixing time • Pump Type: Peristaltic, Gear type • Granulating liquid vessel (e.g., pressurized, heated) Fluid bed granulation • Type of fluid bed • Inlet air distribution plate • Spray nozzle (tip size, type/quantity/ pattern/configuration/position) • Filter type and orifice size • Fill level • Bottom screen size and type • Preheating temperature/time • Method of binder excipient addition (dry/wet) • Granulating liquid temperature • Granulating liquid quantity • Granulating liquid concentration/viscosity • Granulating liquid holding time • Granulating liquid delivery method • Granulating liquid spray rate • Inlet air, volume, temperature, dew point • Atomization air pressure • Product and filter pressure differentials • Product temperature • Exhaust air temperature, flow • Filter shaking interval and duration	• Endpoint measurement (e.g., power consumption, torque, etc.)• Blend uniformity• Potency• Flow• Moisture content• Particle size and distribution• Granule size and distribution• Granule strength and uniformity• Bulk/tapped/true density• API polymorphic form• Cohesive/adhesive properties• Electrostatic properties• Granule brittleness• Granule elasticity • Solid form/polymorph
Drying
• Particle size, distribution • Fines/oversize • Particle shape • Cohesive/adhesive properties • Electrostatic properties • Hardness/plasticity • Viscoelasticity • Brittleness • Elasticity • Solid form/polymorph • Moisture content	Fluidized bed • Inlet air volume, temperature, dew point • Product temperature • Exhaust air temperature, flow • Filter type and orifice size • Shaking interval and duration • Total drying timeTray • Type of tray dryer • Bed thickness/tray depth (depth of product per tray) • Type of drying tray liner (e.g., paper, plastic, synthetic fiber, etc.) • Quantity carts and trays per chamber • Quantity of product per tray • Drying time and temperature • Air flow • Inlet dew pointVacuum/microwave • Jacket temperature • Condenser temperature • Impeller speed • Bleed air volume • Vacuum pressure • Microwave power • Electric field • Energy supplied • Product temperature • Bowl and lid temperature • Total drying time	• Granule size and distribution• Granule strength, uniformity• Flow• Bulk/tapped/true density• Moisture content• Residual solvents• API polymorphic form or transition• Purity profile • Moisture profile (e.g. product temperature vs. LOD) • Potency• Cohesive/adhesive properties • Electrostatic properties
Roller compaction/chilsonation
• Particle size, distribution • Fines/oversize • Particle shape • Cohesive/adhesive properties • Electrostatic properties • Hardness/plasticity • Bulk/tapped/true density • Viscoelasticity • Brittleness • Elasticity • Solid form/polymorph	• Type of roller compactor • Auger (feed screw) type/design (horizontal, vertical or angular) • Deaeration (e.g., vacuum) • Auger (feed screw) speed • Roll shape (cylindrical or interlocking). • Roll surface design (smooth, knurled, serrated, or pocketed) • Roll gap width (e.g., flexible or fixed) • Roll speed • Roll pressure • Roller temperature • Fines recycled (yes or no, # of cycles)	• Ribbon appearance (edge attrition, splitting, lamination, color, etc.)• Ribbon thickness • Ribbon density (e.g., envelop density) • Ribbon porosity/solid fraction• Ribbon tensile strength/breaking force• Throughput rate • API polymorphic form and transition
Extrusion–Spheronization
• Particle size, distribution • Fines/oversize • Particle shape • Cohesive/adhesive properties • Electrostatic properties • Hardness/plasticity • Bulk/tapped/true density • Viscoelasticity • Brittleness • Elasticity • Solid form/polymorph	• Type of extruder (screw or basket)• Screw length, pitch, and diameter• Screw channel depth• Screw blade configuration• Number of screws (single/dual) • Die or screen configuration (e.g., radial or axial) • Die length/diameter ratio• Roll diameter (mm)• Screen opening diameter (mm)• Screw speed (rpm)• Feeding rate (g/min)• Type and scale of spheronizer• Spheronizer load level• Plate geometry and speed• Plate groove design (spacing and pattern)• Air flow • Residence time	• Extrudate• Density• Length/thickness/diameter• Moisture content• API polymorphic form and transition• Content uniformity• Throughput• Pellets after spheronization• Pellets size and distribution • Pellets shape factor (e.g. aspect ratio) • Bulk/Tapped density• Flow properties• Brittleness• Elasticity• Mechanical strength • Friability
Hot melt extrusion
• Particle size, distribution • Fines/oversize • Particle shape • Melting point • Density • Solid form/polymorph • Moisture content	• Screw design (twin/single)• Screw speed• Screw opening diameter (mm)• Solid and liquid feed rates• Feeder type/design• Feed rate• No. of zones• Zone temperatures • Chilling rate	• Extrudate density• Length/thickness/diameter• Polymorphic form and transition• Content uniformity • Throughput
Tabletting
• Particle/granule size and distribution • Fines/oversize • Particle/granule shape • Cohesive/adhesive properties • Electrostatic properties • Hardness/plasticity • Bulk/tapped/true density • Viscoelasticity • Brittleness • Elasticity • Solid form/polymorph • Moisture	• Type of press (model, geometry, number of stations)• Hopper design, height, angle, vibration• Feeder mechanism (gravity/forced feed, shape of wheels, direction of rotation, number of bars)• Feed frame type and speed• Feeder fill depth • Tooling design (e.g., dimension, score configuration, quality of the metal) • Maximum punch load• Press speed/dwell time• Precompression force• Main compression force• Punch penetration depth• Ejection force • Dwell Time	• Tablet appearance• Tablet weight• Weight uniformity• Content uniformity• Hardness/tablet breaking force/tensile strength• Thickness/dimensions• Tablet porosity/density/solid fraction• Friability• Tablet defects• Moisture content• Disintegration • Dissolution
Encapsulation
• Particle/granule size and distribution • Fines/oversize • Particle/granule shape • Cohesive/adhesive properties • Electrostatic properties • Hardness/plasticity • Bulk/tapped/true density • Viscoelasticity • Brittleness • Elasticity • Solid form/polymorph • Moisture	• Machine type• Machine fill speed• Tamping Force• No. of tamps• Auger screw design/speed • Powder bed height	• Capsule appearance• Weight• Weight uniformity• Content uniformity• Moisture content• Slug tensile strength• Disintegration • Dissolution
Pan coating
• Tablet dimensions • Tablet defects • Hardness/plasticity • Density • Porosity • Moisture content	• Type of pan coater (conventional or side-vented)• Pan (fully perforated or partial perforated)• Baffle (design, number, location)• Pan load level• Pan rotation speed• Spray nozzle (type, quantity, pattern, configuration, spray pattern)• Nozzle to bed distance• Distance between nozzles• Nozzle orientation• Total preheating time• Inlet air flow rate, volume, temperature, dew point• Product temperature• Individual nozzle spray rate• Total spray rate• Atomization air pressure• Pattern air pressure• Exhaust air temperature, air flow • Total coating, curing time and drying time	• Coating efficiency• Core tablet weight before and after preheating• Moisture (gain/loss) during preheating• Environmental equivalency factor • Coated drug product (e.g., tablet or capsule) appearance • % weight gain• Film thickness• Coating (polymer and /or color) uniformity• Hardness/breaking force/Tensile strength• Friability• Moisture (gain/loss) during overall process• Residual solvent(s)• Disintegration• Dissolution• Tablet defects • Visual attributes
Fluid bed coating
• Tablet dimensions • Tablet defects • Hardness/plasticity • Density/porosity moisture content	• Type of fluid bed coater• Fluid bed load level• Partition column diameter• Partition column height• Number of partition columns• Air distribution plate type and size• Filter type and orifice size• Filter differential pressure• Filter shaking interval and duration• Spray nozzle (type, quantity, pattern, configuration)• Nozzle port size• Total preheating time• Spray rate per nozzle• Total spray rate• Atomization air pressure• Inlet air flow rate, volume, temperature, dew point• Product temperature• Exhaust air temperature, air flow • Total coating, curing and drying time	• Coating efficiency• Core tablet weight before and after preheating• Moisture (gain/loss) during preheating• Environmental equivalency factor • Coated drug product (e.g., tablet or capsule) appearance • % weight gain• Film thickness• Coating (polymer and /or color) uniformity• Hardness/breaking force/tensile strength• Friability• Moisture (gain/loss) during overall process• Residual solvent(s)• Disintegration• Dissolution• Tablet defects • Visual attributes
Laser drilling
• Size/dimensions • Polymer type membrane thickness	• Conveyor type• Conveyor speed• Laser power• Number of pulses• Type(s) of lens(es)• One or two sided • Number of holes	• Opening diameter (internal and external)• Depth • Shape of the opening