Quality Control Methods

Hopper- The area that holds the powder mixture prior

to compression.
Die Cavity- The area where compression occurs. Its
shape determines the tablet’s size and diameter.
Punches- Components that compress the powder
mixture.
Dosing plow- Pushes a small, precise amount of product
into the die cavity.
Ejection Cam- Pushes the bottom punch upwards,
ejecting the finished tablet from the die cavity.
Particle Size Distribution *Sieving most rapid Mesh #
#linear openings per square inch Techniques:

(a) Sieving
(b) Optical microscopy
(c) Electron microscopy
(d) Sedimentation
(e) Light scattering technique
(f) Adsorption study
(g) Electrolytic resistivity
(h) Permeametry
(i) Coulter counter
(j) Light blockage
SIEVING METHODS:
1. Mechanical Agitation/ Dry sieving- GT
75 micrometer particles (sieve shaker)
Air entrainment methods:
2. Air jet sieving- single sieving
3. Sonic sifter sieving- a nest of sieves
Sample Problem: Given the following date from sieve analysis of a 71.23 g sample of Vitamin C granules.

Sieve No. Initial Weight (g) Final Weight (g)

20 2.62 2.23
40 5.64 5.19
60 20.48 19.83
80 31.17 30.42

1. What is the initial amount of granules present in the receiver?

2. Which of the sieves have already reached the endpoint?
Sample Problem: Given the following date from sieve analysis of a 71.23 g sample of
Vitamin C granules.
Sieve No. Initial Weight Final Weight
(g) (g)
20 2.62 2.23
40 5.64 5.19
60 20.48 19.83
80 31.17 30.42

1. What is the initial amount of granules present in the receiver?

2. Which of the sieves have already reached the endpoint?
The bulk density of a powder is the ratio of the mass of an untapped powder sample to its volume, including
the contribution of the inter particulate void volume. Hence, the bulk density depends on both the density of
powder particles and the spatial arrangement of particles in the powder bed. The bulk density is expressed in
grams per milliliter despite the International Unit being kilogram per cubic meter (1 g/mL = 1000 kg/m3 )
because the measurements are made using cylinders. It may also be expressed in grams per cubic centimeter.
The bulking properties of a powder are dependent upon the preparation, treatment, and storage of the
sample, i.e. how it has been handled. The particles can be packed to have a range of bulk densities and,
moreover, the slightest disturbance of the powder bed may result in a changed bulk density.
The bulk density of a powder is determined either by measuring the volume of a known mass of powder
sample, which may have been passed through a sieve, in a graduated cylinder (Method 1), or by measuring
the mass of a known volume of powder that has been passed through a volumeter into a cup (Method 2) or
has been introduced into a measuring vessel (Method 3).
Methods:
1. Method 1 – Graduated cylinder (The most common method)
Apparatus: 250 mL graduated cylinder
Sample: 100 g
2. Method 2- Volumeter
Apparatus: Scott volumeter
Sample: Constant
3. Method 3- Vessel
Apparatus: 100 mL steel cylindrical vessel
The tapped density is an increased bulk density attained after mechanically tapping a receptacle containing
the powder sample. The tapped density is obtained by mechanically tapping a graduated measuring cylinder
or vessel containing the powder sample. After observing the initial powder volume or mass, the measuring
cylinder or vessel is mechanically tapped, and volume or mass readings are taken until little further volume or
mass change is observed. The mechanical tapping is achieved by raising the cylinder or vessel and allowing it
to drop, under its own mass, a specified distance by one of 3 methods as described below. Devices that rotate
the cylinder or vessel during tapping may be preferred to minimize any possible separation of the mass
during tapping down.
Methods:
1. Method 1 and 2 – Graduated cylinder (The most common
method)
Apparatus: 250 mL graduated cylinder
Sample: 100 g
Differ only in tapping rate.
Procedure:
Tap for 10x (V10)
Tap for 500x (V500)
Tap for 1250x (V1250)
2. Method 3- Vessel
50-60 taps/ minute
200 taps (V200), 400 taps (V400)
Sample Problem:
1. QC analyst Audrey analyzed a new formulation of effervescent granules and obtained
the following data:

Weight of the sample: 100.24 g

Initial volume (untapped): 137 mL
Volume after 10 taps: 134.5 mL
Volume after 500 taps: 130.5 mL
Volume after 1250 taps: 128 mL

Compute for the bulk and tapped density.

Pbulk= mass/ untapped volume

Ptapped= mass/tapped volume
Sample Problem:
1. QC analyst Audrey analyzed a new
formulation of effervescent granules and
obtained the following data:

Weight of the sample: 100.24 g

Initial volume (untapped): 137 mL
Volume after 10 taps: 134.5 mL
Volume after 500 taps: 130.5 mL
Volume after 1250 taps: 128 mL

Compute for the bulk and tapped density.

P bulk= mass/ untapped volume

P tapped= mass/tapped volume
4 COMMONLY REPORTED METHODS FOR TESTING POWDER FLOW:
• Angle of repose,
• Compressibility index or Hausner ratio,
• Flow rate through an orifice- measured as the mass per time flowing from any
container (funnel, cylinder, hopper)
• Shear cell
The angle of repose has been used in several branches of science to characterize the flow
properties of solids. The angle of repose is a characteristic related to inter particulate
friction, or resistance to movement between particles. The angle of repose test results is
reported to be very dependent upon the method used.

The angle of repose is the constant, three-dimensional angle (relative to the horizontal
base) assumed by a cone-like pile of material formed by any of several different methods.
The most common methods for determining the static angle of repose can be classified
based on 2 important experimental variables: – the height of the ‘funnel’ through which
the powder passes may be fixed relative to the base, or the height may be varied as the
pile forms;
1. If the height and the diameter of a powder cone are 3.0 cm and 11. 1 cm
respectively then the powder cone may be characterized as?
Hausner Ratio and Carr’s Index/ Compressibility Index- measure of a powder’s ability to
settle.
Method: Same with bulk and tapped density.
Formula:

HR= Untapped Volume/ Tapped Volume

HR= Tapped density/ bulk density
% CI= Untapped Volume- Tapped Volume/ Untapped Volume X 100
% CI= Tapped Density- Bulk Density/ Tapped Density X 100

Sample Problem:
Determine the HR, CI, and flow properties of the following batches of Cefepime powder.

Batch Number Initial Volume (mL) Tapped Volume (mL)

GB- 0343 96 88

HK- 0577 90 74
Hausner Ratio and Carr’s Index/ Compressibility Index- measure of a powder’s ability to
settle.
Sample Problem:
Determine the HR, CI, and flow properties of the following batches of Cefepime powder.
Batch Number Initial Volume (mL) Tapped Volume (mL)

GB- 0343 96 88

HK- 0577 90 74
IPQC of TABLETS
Tablet hardness/ Breaking Force
-Measure of tablet’s resistance to mechanical stress
-Affects dissolution and disintegration
-“Rule of Thumb”

Hardness Testers:
1. Stokes Monsato- Barrel with a compressible spring held between 2 plungers
2. Strong Cobb- hydraulic pressure or air pump
3. Pfizer- operates like pliers
4. Erweka- suspended weight transmits pressure uniformly
5. Schleuniger- motorized and crushes the tablet in horizontal position. Most commonly
used.
IPQC of TABLETS
Criteria:
1. Compressed Uncoated Tablets: 4-10 Kgs (Ex. Advil and Diclofenac Potassium tablets)
2. Buccal Tablets: 7-10 Kgs (Ex. Acyclovir (Sitavig) and Hydrocortisone (Corlan)
3. Sublingual/ Chewable Tablets: 2-3 Kgs (Ex. Tylenol, Panadol)

Tablet Thickness
Reasons for Measuring:
Consumer acceptance
Affects packaging and operations
Apparatus: Vernier’s Caliper
Acceptance Criteria: +- 5% of the Specifications
1.0 mm Plus minus 5% of the average
Ex.
IPQC of TABLETS
Tablet Weight
Unofficial test based on USP XX
Sample size: 20 units (Get the average)
Weight Variation Tolerance
Average Tablet Weight (mg) % Variation
LT 130 10
130-324 7.5
GT 324 5

Acceptance Criteria:
1. NMT 2 tablets are outside the acceptable tablet weight variation.
2. No unit is outside twice % the acceptable weight variation.
 Average Tablet Weight (mg) % Variation
IPQC of TABLETS
LT 130 10
Tablet Weight
130-324 7.5
GT 324 5

Sample Problem: Twenty units of Metformin tablets (306.65 mg) were weighed
individually and the following date were obtained.

1. What is the acceptable tablet weight range?

2. Did the batch pass the weight variation test?
IPQC of TABLETS
Tablet Weight
Sample Problem: Twenty units of Metformin tablets were weighed individually and the
following date were obtained.

1. What is the acceptable tablet weight range?

2. Did the batch pass the weight variation test?
IPQC of TABLETS
Tablet Weight
Sample Problem: Compute the acceptable tablet weight range of the given formulation
for a batch size of 10, 000 tablets.

Aspirin – 3.25 Kg
Starch- 0. 325 Kg
Cab-o-sil – 0.010 Kg
1. What is the acceptable tablet weight range?
IPQC of TABLETS
Tablet Weight
Sample Problem: Compute the acceptable tablet weight range of the given formulation
for a batch size of 10, 000 tablets.

Aspirin – 3.25 Kg
Starch- 0. 325 Kg
Cab-o-sil – 0.010 Kg
1. What is the acceptable tablet weight range?