Operations to be considered
• Material handling system
• Dry blending
• Granulation
• Drying
• Reduction of particle size
• Compression
Material handling system
In laboratory, materials are simply handled by hand and other
small instruments, but in intermediate or large-scale production, mechanical
means of handling is required.
If the system is used for more than one
product, validated "Cleaning Procedure"
must be done, to prevent
cross contamination.
Examples for material handling system -
Vacuum loading systems, Metering pumps, Screw feed systems.
Dry Blending
Blending is done to ensure good drug distribution. Inadequate blending results in content uniformity.
In large-scale, blender instruments such as V-Cone blender, Double cone blender, Ribbon blender were used.
Prior to blending, agglomerates and lumps are cleared by screening and milling. By doing so, flow problems during blending is avoided.
Parameters considered - Blender loads, Blender size, Mixing speed, Mixing time, Bulk density of the material.
Granulation
Granulation is done, To provide good flow property to the material (uniform tablet), To increase the apparent density of powders, To change the particle size distribution (binding is improved).
Instruments used - Sigma blade mixer, Planetary mixer.
New trend - Multifunctional Processors are used. They are capable of performing all the functions, such as dry blending, wet granulation, drying, sizing and lubrication required to prepare a finished granulation. It is a continuous process.
Transfer of binding fluid/agents by pumping or pouring is difficult. So, in large-scale, binding agent is dispersed in the dry powder prior to granulating.
To improve granulating properties, non aqueous solvents or solutions that are composed of water and water miscible solvents can be used.
Drying
Methods considered - Tray dryer, Fluidized Bed Dryer
Tray dryer (Parameters considered) - Air flow, Air temperature, depth of the granulation on the trays, Monitoring of the process by using moisture and temperature probes.
Drying times at specifies temperature and air flow rates for each product.
Fluidized Bed Dryer (Parameters considered) - Optimum load, Air flow rate, Inlet air temperature, Humidity of the incoming air.
Reduction of particle size
Particle size distribution affects, Flow ability, Compressibility, Uniformity of tablet weight, Content uniformity, Tablet hardness and Tablet color uniformity.
This process is done in two steps,
Step 1: Particle size distribution is determined using a series of stacked sieves of decreasing (large to small size) mesh openings.
Step 2 : Particle size reduction, carried out by passing all the materials through an oscillating granulator, a hammer mill, a mechanical sieving device.
