Pilot Plant Design For Tablets
For pilot plant design for tablets, the primary responsibility of the pilot plant staff is to ensure that the newly formulated tablets developed by product development personnel will prove to be efficiently, economically, and consistently reproducible on a production scale. The Pilot Plant Design For Tablets development should incorporate features necessary to facilitate maintenance and cleanliness. If possible, it should be located on the ground floor to expedite the delivery and shipment of supplies.
1. Formulation and process development.
2. Technology evaluation, scale-up, and transfer.
3. Clinical supply manufacture.
Control Pilot Plant Studies:
1. A pilot plant allows investigation of a product and process on an intermediate scale before large amounts of money are committed to full-scale production.
2. It is usually not possible to predict the effects of a many-fold increase in scale.
3. It is not possible to design a large-scale processing plant from laboratory data alone with any degree of success.
1. Material Handling:
In the laboratory, materials are simply scooped or poured by hand, but in intermediate or large-scale operations, handling of these materials often becomes necessary. If a system is used to transfer materials for more than one product, steps must be taken to prevent cross-contamination. Any material handling system must deliver an accurate amount of the ingredient to the destination. More sophisticated methods of handling materials are vacuum loading systems, metering pumps, screw feed systems.
2. Dry Blending:
The dry blend should take place in the granulation vessel. A larger batch may be dry blended and then subdivided into multiple sections for granulation. All ingredients should be free of lumps, otherwise, it causes flow problems. Screening and/or milling of the ingredients before blending usually makes the process more reliable and reproducible. The equipment used for blending is V-blender, Double cone blender, Ribbon blender, Slant cone blender, Bin blender, Orbiting screw blenders, Vertical and horizontal high-intensity mixers, etc.
- Powders to be used for encapsulation or to be granulated before tableting must be well blended to ensure good drug distribution.
- Inadequate blending could result in drug content uniformity variation, especially when the tablet or capsule is small and the drug concentration is relatively low.
- Ingredients should be lumps-free, otherwise, it could cause flow problems.
The most common reasons given to justify granulating are: to impart good flow properties to the material, to increase the apparent density of the powders, to change the particle size distribution, uniform dispersion of active ingredient, etc. Traditionally, wet granulation has been carried out using, sigma blade mixer, heavy-duty planetary mixer:
- to improve the flow properties.
- to increase the apparent density of the powder.
- to change the particle size distribution so that the binding properties on compaction can be improved.
Direct compression method: A small amount of potent active ingredient can be dispersed most effectively in a carrier granulation when the drug is dissolved in granulating solution and added during the granulating process.
Wet granulation has been carried out by using:
- Sigma blades.
- Heavy-duty planetary mixture.
- High-speed chopper blades are used in the mixing of light powders.
- Multifunctional processors, dry blending, wet granulation, drying, sizing, and lubricating.
- Effect of binding agent.
The most common conventional method of drying a granulation continues to be the circulating hot air oven, which is heated by either steam or electricity. The important factor to consider as part of the scale-up of an oven drying operation are airflow, air temperature, and the depth of the granulation on the trays.
Fluidized Bed Dryer:
- Optimum loads – the rate of airflow.
- Inlet air temperature.
- Data used for small-scale batches (1-5 kg) cannot be extrapolate processing conditions for intermediated scale (100 kg) or large batches.
5. Reduction in Particle Size:
- Particle size to particle size distribution is important to the compression characteristics of a granulation.
- Compression factors may be affected by the particle size distribution, flowability, compressibility, uniformity of tablet weight, content uniformity, tablet hardness, tablet color uniformity.
- Oscillating granulator
- A hammer mill.
- Screening device.
Too large particle size causes:
- Weight variation
Too fine particle size causes:
- Weight variation.
- Both oversized and undersized granulation can adversely affect tablet content uniformity.
- Lubricants and Giants are added to the final blend.
- Attention should be paid to scale-up of the right design is used and blender loads, mixing speeds, mixing timing are properly established.
- In any blending operation segregation and mixing occurs simultaneously, both processes are function of a particle size, shape, hardness, density and dynamics of the mixing action.
- Low-dose active ingredients are directly compressed.
- Planetary type mixer
- Twin shell mixture
- Cone type
Overloading in a blender:
- Retards the free flow of granules
- Reduces the efficiency
- Causes content un-uniformity
If the load is too small:
- Powder blend slides rather than roll in a blender.
- It causes improper mixing.
A dry powder blend cannot be directly compressed because of poor flow or compression properties. This is done on a tablet press designed for slugging, which operates at pressures of about 15 tons, compared with a normal tablet press, which operates at a pressure of 4 tons or less. Slugs range in diameter from 1 inch, for the more easily slugged material, to ¾ inch in diameter for materials that are more difficult to compress and require more pressure per unit area to yield satisfactory compacts. If an excessive amount of fine powder is generated during the milling operation, the material must be screened and finely recycled through the slugging operation.
The ultimate test of the tablet formulation and granulation can be compressed on a high-speed tablet press.
Steps involved during compression:
1. Filling empty die cavity with granulation.
2. Pre-compression of granules.
3. Compression of granules.
4. Ejection of tablet from the die cavity.
Compression characteristics can be evaluated by press speed equal to normal production speed. Then detect the problems such as,
- Sticking to punch surface
- Tablet hardness
- Weight variation
Granules must be delivered at an adequate rate.
9. Tablet Coating:
Pan and fluidized coating:
- Optimum tablet load.
- Operating tablet bed temperature.
- Drying airflow rate and temperature.
- The solution application rate.
- The size and shape of the nozzle aperture (for airless sprayer).
- The atomizing air pressure and the liquid flow rate (for air atomized sprayers).
- Fixed operating parameters.
- Variable operating parameters.
- Other parameters; Pan Loading (kg), Solid content of coating suspension (% w/w), Spray gun dynamics, Drying Air, Inlet air temperature (°C), Gun to tablet bed distance, Coating System Spray rate (g min−1), Quantity of coating applied (% w/w), Atomizing air pressure (psi, bar), Air Pressure (psi, bar), Pan speed Number of spray guns.
Fluidized bed coating:
- Batch size.
- Drying/fluidizing air volumes.
- Spray nozzle dynamics.
- Spray evaporation rate.
- Conventional coating pan.
- Perforated pans of fluidized-bed coating column.
- Film coating.
(i) Tablet must be sufficiently hard to withstand the tumbling to which they are subjected while coating.
(ii) Operation conditions to be established for pan or column operation are optimum tablet load, operating tablet, bed temperature, drying air flow rate, temperature, solution application rate.
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