2. Blending: The powder which is to be used for formulation should be well blended

to ensure efficient drug distribution. Inadequate/improper blending can cause a

discrete portion of batch either of low or of high potency. So, it is essential to ensure

that all ingredients are thoroughly blended with no lumps and agglomerates. In

Fig. 2.3: Different aspects of general considerations

General Considerations and Pilot-Plant Considerations for Different Dosage Forms 15

any blending operation, both operations, i.e. segregation and mixing occur side by

side. Screening and milling techniques are used for making this procedure more

reproducible and reliable (Table 2.1).

Table 2.1: Scale-up considerations during blending

Equipment used Scale-up considerations

V-blender The following should be of primary consideration

Double cone blender during blending:

Ribbon blender • Time of blending

Slant cone blender • Blender loading

Bin blender • Size of blender

Orbiting screw blender's horizontal • Mixing times

and vertical high intensity mixers • Mixing speeds

• Material characteristics

• Bulk density of raw material

• Particle abrasion (in case of use of high shear

mixers with spiral screws and blades)

3. Granulation: Granulation is the most important step in tablet formation or

sometimes in encapsulation. Good granulation will ensure good flow property of

the material, increase the apparent density of powder, affect particle size distribution,

and ensure uniform dispersion of active pharmaceutical ingredient (Table 2.2).

Specialised Granulation Procedures

a. Slugging (dry granulation): This is used for the dry powder that has poor flow

properties and hence cannot be directly compressed. A tablet press having pressure

of about 15 tons is used for slugging. The slugs have a diameter of 3/4th of inch to

1 inch depending upon the difficulty of compressing the powder. The size of slug

decreases with increasing difficulty in compressing. Less size increases pressure

per unit area for slugging. In case of excessive amount, the material should be

screened and recycled through slugging operation.

b. Dry compaction: In this process the powder is passed between two rollers having

pressure of up to 10 tons per linear inch. This process is generally opted for the

material of very low density, e.g. aluminium hydroxide.

Table 2.2: Scale-up considerations during granulation

Equipment used Scale-up considerations

Sigma blade mixers Type of granulation

Heavy-duty planetary mixer Dry granulation

Fluidized bed dryer Wet granulation

Multifunctional processors (capable of Characteristics of ingredient used like

performing all functions required to prepare hydrophobic or hydrophilic in nature,

finished granulation like dry blending, wet thermolabile or thermostable, solubility, etc.

granulation, drying, sizing, etc.)

16 Industrial Pharmacy II

4. Binders: The binders have important place in tablet production. Binders are used

to make powders more compressible so that tablets can be made which are more

resistant to breakage while handling (Table 2.3).

5. Drying: After granulation drying is an essential step. Circulating hot air oven (heated

by steam or electricity) is the most conventional method used for drying. But during

scale-up certain factors regarding hot air oven needs to be considered like:

i. Airflow

ii. Air temperature