Understanding Granule Properties: Crucial Steps in Pharmaceutical Manufacturing .

Characterization of Granules

APPARATUS:

  Weighing balance

Volumetric cylinder

 Funnel

Tripod Stand

CHEMICAL REQUIRED

. Granules

INTRODUCTION:

The preparation of essentially all dosage forms involves the handling of solid materials... Among all finished products, solid dosage forms are the most predominant in terms of volume and value. The importance of solid-handling properties, especially flow properties cannot be overemphasized. The flow properties of solids have a great impact on the tableting and encapsulation processes since these dosage forms manufacturing processes require the flow of powder materials from a storage container to a filling station, such as tablets dies capsule fillers. The flow properties of solids also have a great influence on the mixing and de-mixing of powders that take place before tableting or encapsulation.

Forces that can act between solid particles are:

1) Frictional Forces

2) Surface Tension Forces

3) Electrostatic Forces

4) Cohesive Forces

5) Mechanical Forces caused by interlocking of particles of irregular shape.

Some simple criteria are useful to predict flow properties from measurements made on a static heap or bed of powder.

1. Flow Rate

2. Angle of Repose

3. Bulk Demily and Tapped Density

4. Compressibility Index

5. percentage yield 

POWDER FLOW PROPERTIES

(1) Flow Rate:

Flow Rate is defined as the amount of powders (in grams) allowed to flow/pass through the famel per time (in seconds) required to pass. Flow time is measured using the "Free Standing Cone and Fixed Funnel Method".

(2) Angle of Repose:

The angle of repose is the maximum angle between the free-standing free-standing surface of a powder heap and the horizontal plane. A static heap of powder, with only gravity acting upon it, will tend to form a conical mound. One limitation exists: the angle to the horizontal cannot exceed certain values, and this is known as the Angle of Repose (0).

One of the methods used to measure the angle of repose is the fixed-funnel and free-standing cone method.

Tan 0 = H/R or 21/D

0 = Tan-1 (H/R)

Where;

 alpha is the angle of repose, 

H is the height of the cone, 

R is the radius of the cone.

The angle of Repose (Degrees) ---------- Type of Flow

20.-------------Excellent

20-30 ----------Good

30-34 -------------Passable a

>40 ----------------Very Poor

It May be improved by Glidant, e.g. 0.2% Acrosil.

(3).   Bulk and Tapped Density:

The bulk and tapped density of pharmaceutical powders are often measured for processability. The tapped density is measured for two primary purposes: (i) the tapped value is more reproducibly measured than the bulk value, and (ii) the "flowability" of a powder is inferred from the ratio of these two measured densities. Tapped density by the USP method is determined by a linear progression of the number of taps. This is done by measuring the initial volume (Bulk Volume) of the sample and recording its weight. From this data we can calculate the bulk density by:

Bulk Density = weight/volume grams per ml

By measuring the volume after the system is allowed to tap until reaching a constant volume (Tapped Volume) of the sample and by using these data we calculate the tapped density by: 

Tapped Density = weight/volume = grams per ml

How the Bulk Density and Tapped Density change

The most important factor that changes these densities is particle size distribution. Suppose that we have two granules A and B. A has a narrow particle size distribution and B has a wide particle size distribution. When A is poured and because of the uniform particle size, the granules will arrange with the same spaces that cannot be filled with small particles, obviously because there are no fines to fill these spaces. Accordingly, when this powder is tapped, a small volume change is expected, again because there are no fine particles to move into the formed spaces upon pouring. On the contrary, B upon pouring will have interspaces among the large particles than between the small particles. The large spaces between the large particles will be filled with the small particles upon tapping and consequently large reduction in the volume is expected.

(4) Compressibility Index

Bulk and tapped densties can be used to calculate an index called the Compressibility Indes as the folleoving

Compressibility index = [(tapped dersity-bulk density)/tapped density ] × 100

Carr's Index as an indication of powder flow

Carr's Index (%) -----------Type of Flow

5-15  ----------------Excellent 

12-16 -------------Good

18-21 --------------Fair to passable

23-35  --------------Poor 

33-38  --------------Very Poor.

>40   ----------------  Extremely Poor

It May be improved by Glidant, e.g. 0.2% Acrosil.

(5) Moisture Content:

Water content or moisture content is the quantity of water contained in a material, such as soil (called soil moisture), rock, ceramic, or wood on a volumetric or gravimetric hasis. The property is used in a wide range of scientific and technical areas, and is expressed as a ratio, which can range from 0 (completely dry) to the value of the materials porosity at saturation.

1) Loss On Drying (LOD)

 calculated as follows:

LOD weight of water in sample/total weight of wet sample x 100

A weighed sample is placed on the balance and allowed to dry until it is at a constant weight. The water lost by evaporation is read directly from the percent LOD scale.

2) Moisture Content:

% MC = weight of water in sample/total weight of dry sample × 100