| GENERAL UNIT OPERATION INVOLVED IN
MANUFACTURING | 1 MILLING
2 MIXING
3 GRANULATION
4 DRYING
5 FILLING |
| Process of reducing the particle size | MILLING |
| MILLING 3 BASIC ACTIONS | 1) Attrition - Breaking down of materials by rubbing
action between two surfaces
2) Rolling - The use of heavy rollers to crush ang
pulverize the materials
3) Impact - Involves the operation of hammers or bars at
high speed; In here, they strike the lamps against
each other or against the wall of the chamber
ARI |
| 1 Breaking down of materials by RUBBING
ACTION BETWEEN TWO SURFACES
2 The use of HEAVY ROLLERS TO CRUSH ang
PULVERIZE the materials
3 Involves the operation of HAMMERS OR BARS AT
HIGH SPEED; In here, they strike the lamps against
each other or against the wall of the chamber | 1 Attrition
2 Rolling
3 Impact |
| MIXING - Uses several equipment: | 1 Tumbling Mixers or Blenders
2 High Speed Mixer Granulators
3 Fluidized-bed Mixers
4 Agitator Mixers |
| COMMONLY USED for GRANULES and FREE-FLOWING POWDERS;
Their containers are GENERALLY MOUNTED so that they can be ROTATED ABOUT AN AXIS | Tumbling Mixers or Blenders |
| Aside from mixing, this can also be USED FOR GRANULATION OF PRODUCTS | High Speed Mixer Granulators |
| MAIN USE is to DRY THE GRANULES or DECOATING THE MULTIPARTICLES | Fluidized-bed Mixers |
| Usually depend on the motion of the BLADE OR PADDLE through the product;
Main mechanism is CONVECTIVE MIXING (inversion of the powderbed using blades or paddles in which the large mass of material moves from one place to another.);
Using this equipment, DEADSPOTS MAY NOT BE
ELIMINATED during the process, SOME OF THE PARTICLES WILL NOT BE MIXED | Agitator Mixers |
| A process in which the POWDER PARTICLES
are made to ADHERE TO FORM A LARGER MULTIPARTICLE ENTITIES
Typically, the size of these granules are from 0.2 TO 4 MM while for granules intended for tableting purposes and capsulation are from 0.2 TO 0.5 MM | GRANULATION |
| GRANULATION
1 Typically, the size of these granules are from __
2 while for granules INTENDED FOR TABLETING PURPOSES and CAPSULATION are from __ | 1) 0.2 TO 4 MM
2) 0.2 TO 0.5 MM |
| GRANULATION METHODS | 1 Wet Granulation
2 Dry Granulation
3 Direct Compression |
| Involves the MASSING OF A MIX OF DRY PARTICLES using a GRANULATING FLUID
OLDEST AND WIDELY USED METHOD which involves WET MASSING
The WET MASS IS FORCED THROUGH A SEIVE to PRODUCE GRANULES which are then dried
The granulating fluids usually used are volatile
solvents (Ethanol, Isopropranol, and Water)
(STATE THE ADV & DISADV) | Wet Granulation
ADV:
1 Improves COHESIVENESS & COMPRESSIBILITY of powders with formulation of granules
2 SUITABLE for high dosage drugs with POOR FLOW or COMPRESSIBILITY
3 GOOD DISTRIBUTION and UNIFORM CONTENT for soluble low-dosage drugs
4 GOOD COLOR DISTRIBUTION
5 Ensures fixed composition of each granule during processing, transport, and handling
6 IMPROVES the DISSOLUTION RATE of HYDROPHOBIC
DISADV:
1 Very costly
2 time and labor-consuming
3 NOT USEFUL for WATER and HEAT-SENSITIVE DRUGS |
| Wet Granulation
GENERAL STEPS: | 1. Milling of raw materials.
2. Weighing of raw materials.
3. Dry mixing of milled raw materials by adding the active ingredient, diluent, and internal disintegrant.
4. Wet mixing: incorporating of binder solution (granulating fluid)
5. Granulation and screening of the damp mass using 6-12 mesh screen.
6. Drying.
7. Dry screening through small mesh screen (no. 14-20).
8. Final mixing: addition of lubricant and external disintegrant; From there, it is now ready for further processing either to be encapsulated or to be compressed into powders.
9. Compression. |
| The PRIMARY POWDER PARTICLES are AGGREGATED under a HIGH PRESSURE
Usually DONE THROUGH SLUGGING (a heavy-duty tablet press is used and the resulting product is a large tablet that is broken down into smaller pieces) or ROLLER COMPACTION (the powder is squeezed between 2 rollers to produce sheet of materials that will be broken down into smaller pieces)
This method may be USED FOR DRUGS THAT DO NOT COMPRESS WELL AFTER WET GRANULATION or those which are SENSITIVE TO MOISTURE
Active tablets are usually Thiamine, Thiamine hydrochloric, Aspirin, Ascorbic acid, and Magnesium
hydroxide
(STATE THE ADV & DISADV) | Dry Granulation
adv:
Very useful for water and heat-sensitive materials
disadv:
1 NOT permit uniform color distribution
2 tendency to CREATE MORE DUST (NO GRANULATING FLUID) |
| Dry Granulation
1 Active tablets are usually | 1 Thiamine
2 Thiamine hydrochloric
3 Aspirin
4 Ascorbic acid
5 Magnesium hydroxide |
| Dry Granulation GENERAL STEPS | 1. Milling.
2. Weighing.
3. Mixing: AI, diluent, and a portion of lubricant.
4. Slugging or precompression.
5. Granulation and Sieving.
6. Final mixing: Lubricant and Disintegrant.
7. Compression. |
| The PREFERRED METHOD IN GRANULATION
TABLETS are COMPRESSED DIRECTLY from powder blends of active and suitable ingredients
USES DIRECTLY COMPRESSIBLE VEHICLE such as
Anhydrous lactose, Spray-dried lactose, Crystalline
sorbitol, Dicalcium phosphate dihydrate, Granular
mannitol, and Avicel
The ingredients incorporated here SHOULD POSSESS
INHERENT COHESIVENESS & GOOD FLOW PROPERTIES
(STATE THE LIMITATIONS) | Direct Compression
LIMITATIONS:
- Stratification-variation in content with differences
in size and density
- Drug limited to 30% of tablet weight unless
directly compressible
- Interaction between amine drugs and spray-dried
lactose
- Development of static charges which prevents
uniform distribution |
| Direct Compression
USES DIRECTLY COMPRESSIBLE VEHICLE such as | 1 Anhydrous lactose,
2 Spray-dried lactose,
3 Crystalline sorbitol,
4 Dicalcium phosphate dihydrate,
5 Granular mannitol,
6 Avicel |
| Direct Compression GENERAL STEPS | 1. Milling
2. Weighing
3. Mixing
4. Compression |
