Granules. Presented By: Dr. Abdel Naser Zaid. Granules are aggregations of fine particles of powders in a mass of about spherical shape. Why we prepare granules when we have powders? To avoid powder segregation,
Dr. Abdel NaserZaid
Granules are aggregations of fine particles of powders in a mass of about spherical shape.
if the powder is composed of particles with different dimensions & different densities, a separation between these particles will occur.
Higher flowability gives better filling of the dies or containers, during a volumetric dosage.
To improve the compressibility of powders.
The granulation of toxic materials will reduce the hazard of generation of toxic dust, which may arise during the handling of the powders.
Materials, which are slightly hygroscope, may adhere & form a cake if stored as a powder.
These granules are used to prepare an instant solution or suspension.
Granules, can be packaged as:
Usually, granules have an excellent compressibility,
Pharmaceutical powders that were mixed homogeneously together are compressed to obtain large tablets.
The high compression forces are obtained by using one of the following procedures:
These machines are provided with dies of 2-3 cm diameters (the fine powders have low flowability)
large dies are easily filled in this case, the dies travel between two punches, which press the powder forming large tablets, with 2-3 cm of diameters.
The powder mixture flow between two rollers to form a compressed sheet.
These large tablets or sheets are milled.
The milled sheets are sieved.
These granules are poorly water-permeable due to the low porosity.
So, water can’t permeate them easily in order to disintegrate & dissolve them.
This will extremely reduce the velocity of dissolution & so the bioavailability of the active material.
Vice versa if the granules have high porosity the molecules of water can penetrate easily into the pores, & disintegrate the granules.
High Porosity means high specific surface area, leading to an increasing in the dissolution velocity of the granules, & thus their bioavailability.
Thus, we can say that the dry granulation method is used only for those powders, which cannot be granulated with the wet granulation method.
Characteristics of the granulating liquid:
If the powder is soluble in the solvent, a solution or suspension will be obtained instead of the paste.
From another side, if the solvent cannot absolutely dissolve the powder, we cannot obtain the liquid forces, which stick together the powder particles.
The fraction of powder, which dissolves in the solvent, & then re-crystallizes, after the drying, will form bridges between the particles of the powder.
This syrup has less dissolving capacity than the pure water, because the majority of water molecules are involved in the hydration & dissolving of the sugar molecules instead of the powder molecules.
But if the powder is water insoluble,
A co-solvent is recommended.
This is a mixture between water & another water-soluble pharmaceutical solvent with high dissolving capacity toward the powder.
We can also use a water solution of polymers,
The evaporation of water can determine the adhesion between the particles of the powder.
Such viscose solutions determine the adhesion of the particles of the powders,
When water evaporates the gelatin solidifies between the two particles of powder and maintain them stuck together.
Pre-gelatinized starch, which has the characteristic to swell in a cold water.
The granules obtained in this way are called agglutinated granules.
To achieve this, many granulators are available (see industrial pharmacy):
we can measure the energy that we must provide to the system in which we carry out the wetting process.
Put the powder for granulation in the granulator,
Add gradually the granulating liquid,
Then mix by the use of electrical motor
This motor measures the absorbed power in function of the time & so in function of the putted liquid.
Electrostatic bonds (less important),
Liquid bonds (more important).
These bonds start to bind together the powder particles & to form the granules.
Therefore the equipment meet higher resistance to maintain constant the number of rounds/minute.
The addition of further liquid, will give phase 5 where we note a sharp drop in the absorbed power, because the granulate will be transformed in a suspension.
In this manner we have an idea about the percentage quantity of the granulating liquid, which we have to add, by evaluating the curve.
Water is more difficult to be eliminated than the organic solvents, therefore the water gives some problems:
Water of Crystallization,
It is very difficult to be eliminated without causing the decomposition of the product or variation of its crystalline form.
The amount of water, which was absorbed by a drug present in a moist air, this amount depends on the nature of the drug & the relative humidity of the air.
Imbibition of water,
The amount of water, which impregnates the granules, this water is easy to be eliminated by simple evaporation.
If we use a hydrophilic polymer solution, as a granulating liquid, & we proceed for long time in the drying process, the hydrophilic polymer will assume a glassy consistency.
These glassy characteristics cause the fragmentation of the granules during the following manufacturing processes.
Thus, a certain quantity of moisture is useful to improve the manipulation of the granules.
Fluidized Bed Drier,
The last step is the classification according to particles dimension:
If we have big granules we can use big measuring tool, while if the granules have small size, we can use small measuring tool.
The most critical problem is :
In this case:
it is not only important to have granules with equal dimensions, but
it is also important that the size of these granules are within a certain range, which is in function with the diameter of the die.
so to obtain tablets, which remain within the limits of the weight uniformity.
If we have a die with diameter of 3/16 of inch, we should prepare granules, which pass through a sieve with mesh 20 (20 mesh /1 linear inch).
If we have a die with diameters of 7/16 inch, we have to have granules with dimensions that pass through a sieve of mesh 12.
The granules must be:
packaged in order to be used as final pharmaceutical dosage form, or
added to other substances for example to prepare the tablets,
So, we must avoid the transformation of the granules into powder during the manipulation processes.