FARMACEUTISCHE TECHNOLOGIE
PART 1: AGGLOMERATIE PROCESSEN ............................................................................................................. 6
THEORETISCHE ACHTERGROND EN HET MECHANISME VAN GRANULATIE ...............................................................................6
Algemene mechanismen van droge granulatie ...............................................................................................6
Electrostatic interactions ...............................................................................................................................................6
Molecular interactions ...................................................................................................................................................6
Immobile liquid films ......................................................................................................................................................6
Capillary forces ...............................................................................................................................................................6
Formation of solid bridges .............................................................................................................................................6
Mechanical interlocking of particles ..............................................................................................................................6
Binding mechanisms during wet granulation ..................................................................................................7
Pendular state ................................................................................................................................................................7
Funicular state ................................................................................................................................................................7
Capillary state.................................................................................................................................................................7
Droplet state ..................................................................................................................................................................7
Formation of solid bridges .............................................................................................................................................7
Granule growth steps and mechanisms...........................................................................................................7
BINDERS IN GRANULATIE PROCESSEN ............................................................................................................................7
Type of binder ..................................................................................................................................................7
Natural polymers............................................................................................................................................................7
Synthetic polymers .........................................................................................................................................................7
Sugars .............................................................................................................................................................................7
Efficiency of binding: influence of API or excipients .........................................................................................7
Efficiency of binding: influence of binder/solvent system ................................................................................7
Efficiency of binding: influence of storage conditions......................................................................................7
HIGH SHEAR GRANULATIE ...........................................................................................................................................7
Wet granulation process steps ........................................................................................................................7
Advantages and disadvantages .......................................................................................................................7
Balance between liquid addition and kneading ...............................................................................................7
Formulation variables ......................................................................................................................................7
Process variables .............................................................................................................................................7
End point determination ..................................................................................................................................7
LOW SHEAR GRANULATIE ............................................................................................................................................7
SMELT AGGLOMERATIE EN GRANULATIE.........................................................................................................................7
ZWEEFBED GRANULATIE .............................................................................................................................................7
Fluidization ......................................................................................................................................................8
Description of the system ................................................................................................................................8
Air handling system ........................................................................................................................................................8
Container and air distributor..........................................................................................................................................8
Spray nozzle ...................................................................................................................................................................8
Disengagement area and process filters ........................................................................................................................8
Exhaust blower, control system, liquid delivery system ................................................................................................8
Granulation mechanism-process .....................................................................................................................8
Process and formulation parameters ..............................................................................................................8
VERGELIJKING VAN DE GRANULATIE PROCESSEN ..............................................................................................................8
SPROEI DROGEN........................................................................................................................................................8
Description of the system ................................................................................................................................8
Description of the process: atomization ..........................................................................................................8
Application of centrifugational forces ............................................................................................................................8
Kinetic energy nozzle......................................................................................................................................................8
Pressure nozzle ..............................................................................................................................................................8
Ultrasonic nozzle ............................................................................................................................................................8
Description of the process: drying of droplets and particle collection .............................................................8
Process and formulation parameters ..............................................................................................................8
Droplet and particle formation ........................................................................................................................8
, Process parameters with influence on particle size .........................................................................................8
Applications .....................................................................................................................................................8
DUBBELSCHOEF EXTRUSIE ...........................................................................................................................................8
Extruder design and components ....................................................................................................................8
Barrel ..............................................................................................................................................................................8
Screw elements: conveying screws – mixing screws......................................................................................................8
Die ..................................................................................................................................................................................9
Extrusion process .............................................................................................................................................9
Feed rate ........................................................................................................................................................................9
Screw speed ...................................................................................................................................................................9
Barrel temperature ........................................................................................................................................................9
Wet granulation...............................................................................................................................................9
Importance of rheology during HME and MG..................................................................................................9
EXTRUSIE SFERONISATIE ..............................................................................................................................................9
Description of the process................................................................................................................................9
Dry mixing of powders ...................................................................................................................................................9
Wet massing (granulation step) .....................................................................................................................................9
Extrusion ........................................................................................................................................................................9
Spheronization ...............................................................................................................................................................9
Drying .............................................................................................................................................................................9
COMPRESSIE EN COMPACTIE ........................................................................................................................................9
Mechanism ......................................................................................................................................................9
Characterization of the process .......................................................................................................................9
Force-displacement profile ............................................................................................................................................9
Volume- pressure profile ...............................................................................................................................................9
Heckel equation .............................................................................................................................................................9
Bonding mechanisms .......................................................................................................................................9
Factors that influence hardness of compact, tablets .......................................................................................9
Quantification of hardness of tablets ..............................................................................................................9
Post compaction changes in tablet strength ...................................................................................................9
Relation between material properties and tablet strength .............................................................................9
Manufacturing of tablets .................................................................................................................................9
Dry granulation ..............................................................................................................................................10
Comparison between granulation and DC .....................................................................................................10
Technical problems during tablet manufacturing..........................................................................................10
Uniformity of mass (Ph. Eu) ...........................................................................................................................10
Excipients used in tablet formulations ...........................................................................................................10
PART 2: FILM COATING ................................................................................................................................. 10
REDENEN OM TE COATEN ..........................................................................................................................................10
PROCES .................................................................................................................................................................10
zweefbed granulatie ......................................................................................................................................10
top spray ......................................................................................................................................................................10
bottom spray ................................................................................................................................................................10
roterend, centrifugale spray ........................................................................................................................................10
geperforeerde pansytemen ...........................................................................................................................10
proces parameters .........................................................................................................................................10
FILMCOATING VAN WATERIGE SYSTEMEN .....................................................................................................................10
(Film coating from a polymer solution: film formation mechanism) .............................................................10
Film formation mechanism ............................................................................................................................10
MATERIALEN OM TE COATEN .....................................................................................................................................10
Immediate release .........................................................................................................................................10
Modified release: polymers that dissolve at a specific pH .............................................................................10
modified release: insoluble polymers.............................................................................................................10
plasticizers .....................................................................................................................................................10
pore forming materials ..................................................................................................................................10
PART 1: AGGLOMERATIE PROCESSEN ............................................................................................................. 6
THEORETISCHE ACHTERGROND EN HET MECHANISME VAN GRANULATIE ...............................................................................6
Algemene mechanismen van droge granulatie ...............................................................................................6
Electrostatic interactions ...............................................................................................................................................6
Molecular interactions ...................................................................................................................................................6
Immobile liquid films ......................................................................................................................................................6
Capillary forces ...............................................................................................................................................................6
Formation of solid bridges .............................................................................................................................................6
Mechanical interlocking of particles ..............................................................................................................................6
Binding mechanisms during wet granulation ..................................................................................................7
Pendular state ................................................................................................................................................................7
Funicular state ................................................................................................................................................................7
Capillary state.................................................................................................................................................................7
Droplet state ..................................................................................................................................................................7
Formation of solid bridges .............................................................................................................................................7
Granule growth steps and mechanisms...........................................................................................................7
BINDERS IN GRANULATIE PROCESSEN ............................................................................................................................7
Type of binder ..................................................................................................................................................7
Natural polymers............................................................................................................................................................7
Synthetic polymers .........................................................................................................................................................7
Sugars .............................................................................................................................................................................7
Efficiency of binding: influence of API or excipients .........................................................................................7
Efficiency of binding: influence of binder/solvent system ................................................................................7
Efficiency of binding: influence of storage conditions......................................................................................7
HIGH SHEAR GRANULATIE ...........................................................................................................................................7
Wet granulation process steps ........................................................................................................................7
Advantages and disadvantages .......................................................................................................................7
Balance between liquid addition and kneading ...............................................................................................7
Formulation variables ......................................................................................................................................7
Process variables .............................................................................................................................................7
End point determination ..................................................................................................................................7
LOW SHEAR GRANULATIE ............................................................................................................................................7
SMELT AGGLOMERATIE EN GRANULATIE.........................................................................................................................7
ZWEEFBED GRANULATIE .............................................................................................................................................7
Fluidization ......................................................................................................................................................8
Description of the system ................................................................................................................................8
Air handling system ........................................................................................................................................................8
Container and air distributor..........................................................................................................................................8
Spray nozzle ...................................................................................................................................................................8
Disengagement area and process filters ........................................................................................................................8
Exhaust blower, control system, liquid delivery system ................................................................................................8
Granulation mechanism-process .....................................................................................................................8
Process and formulation parameters ..............................................................................................................8
VERGELIJKING VAN DE GRANULATIE PROCESSEN ..............................................................................................................8
SPROEI DROGEN........................................................................................................................................................8
Description of the system ................................................................................................................................8
Description of the process: atomization ..........................................................................................................8
Application of centrifugational forces ............................................................................................................................8
Kinetic energy nozzle......................................................................................................................................................8
Pressure nozzle ..............................................................................................................................................................8
Ultrasonic nozzle ............................................................................................................................................................8
Description of the process: drying of droplets and particle collection .............................................................8
Process and formulation parameters ..............................................................................................................8
Droplet and particle formation ........................................................................................................................8
, Process parameters with influence on particle size .........................................................................................8
Applications .....................................................................................................................................................8
DUBBELSCHOEF EXTRUSIE ...........................................................................................................................................8
Extruder design and components ....................................................................................................................8
Barrel ..............................................................................................................................................................................8
Screw elements: conveying screws – mixing screws......................................................................................................8
Die ..................................................................................................................................................................................9
Extrusion process .............................................................................................................................................9
Feed rate ........................................................................................................................................................................9
Screw speed ...................................................................................................................................................................9
Barrel temperature ........................................................................................................................................................9
Wet granulation...............................................................................................................................................9
Importance of rheology during HME and MG..................................................................................................9
EXTRUSIE SFERONISATIE ..............................................................................................................................................9
Description of the process................................................................................................................................9
Dry mixing of powders ...................................................................................................................................................9
Wet massing (granulation step) .....................................................................................................................................9
Extrusion ........................................................................................................................................................................9
Spheronization ...............................................................................................................................................................9
Drying .............................................................................................................................................................................9
COMPRESSIE EN COMPACTIE ........................................................................................................................................9
Mechanism ......................................................................................................................................................9
Characterization of the process .......................................................................................................................9
Force-displacement profile ............................................................................................................................................9
Volume- pressure profile ...............................................................................................................................................9
Heckel equation .............................................................................................................................................................9
Bonding mechanisms .......................................................................................................................................9
Factors that influence hardness of compact, tablets .......................................................................................9
Quantification of hardness of tablets ..............................................................................................................9
Post compaction changes in tablet strength ...................................................................................................9
Relation between material properties and tablet strength .............................................................................9
Manufacturing of tablets .................................................................................................................................9
Dry granulation ..............................................................................................................................................10
Comparison between granulation and DC .....................................................................................................10
Technical problems during tablet manufacturing..........................................................................................10
Uniformity of mass (Ph. Eu) ...........................................................................................................................10
Excipients used in tablet formulations ...........................................................................................................10
PART 2: FILM COATING ................................................................................................................................. 10
REDENEN OM TE COATEN ..........................................................................................................................................10
PROCES .................................................................................................................................................................10
zweefbed granulatie ......................................................................................................................................10
top spray ......................................................................................................................................................................10
bottom spray ................................................................................................................................................................10
roterend, centrifugale spray ........................................................................................................................................10
geperforeerde pansytemen ...........................................................................................................................10
proces parameters .........................................................................................................................................10
FILMCOATING VAN WATERIGE SYSTEMEN .....................................................................................................................10
(Film coating from a polymer solution: film formation mechanism) .............................................................10
Film formation mechanism ............................................................................................................................10
MATERIALEN OM TE COATEN .....................................................................................................................................10
Immediate release .........................................................................................................................................10
Modified release: polymers that dissolve at a specific pH .............................................................................10
modified release: insoluble polymers.............................................................................................................10
plasticizers .....................................................................................................................................................10
pore forming materials ..................................................................................................................................10
