STANDARD OPERATING PROCEDURE

TITLE

: FINISHED PRODUCT QUALITY CONTROL PROTOCOLS FOR

ALUMINUM HYDROXIDE AND MAGNESIUM HYDROXIDE SUSPENSION,
USP

FUNCTION

: REGULATORY AND QUALITY ASSURANCE DEPARTMENT

TABLE OF CONTENTS
1. PURPOSE ................................................................................................................. 2
2. SCOPE ...................................................................................................................... 3
3. DEFINITIONS ............................................................................................................ 4
4. MATERIALS AND EQUIPMENT.............................................................................. 5
5. ROLES AND RESPONSIBILITIES........................................................................... 6
6. PROCEDURES.......................................................................................................... 7
7. ACCEPTANCE CRITERIA........................................................................................ 12
8. REFERENCES........................................................................................................... 13

This document describes the quality control parameters and specifications for the product,
Aluminum Hydroxide and Magnesium Hydroxide suspension, as stated by the United States
Pharmacopoeia. The sample to be tested is Aluminum Hydroxide and Magnesium Hydroxide, 225 mg/ 200
mg/ 5 mL suspension, manufactured by Drugmakers Laboratories, Inc. It will be subjected to assay,
deliverable volume test, particle size distribution test, sedimentation volume test, redispersibility, test for
viscosity, pH and organoleptic evaluation.
The Quality Assurance Department of Quales Philippines ensures that proper test procedures,
equipment, standard operating procedures (SOPs) and current good manufacturing practices (cGMPs) are
being followed during the Finished Product Quality Control (FPQC) of the drug product.
1. PURPOSE:
Generally, the Final Product Quality Control (FPQC) aims to determine if the finished drug
product
possesses appropriate quality properties based on the standards set by USP. For more systematic
and efficient work, the company has set protocols for the quality control parameters and specifications
for the drug.
1.1. For the Assay of Aluminum Hydroxide and Magnesium Hydroxide Suspension, the study aims
to: determine the strength or content of the active pharmaceutical ingredient in the dosage form; and
determine whether the actual amount of active ingredient in the sample complies with its label claim.
1.2. For the Deliverable Volume Test, the study aims to: ensure that the volume of dosage form declared
on the label will be delivered by the product when transferred from the original container.
1.3. For the Particle Size Distribution Test, the study aims to: determine the division of different particle
size of the product and distribution of the active ingredient in the drug product
1.4. For the Sedimentation Volume Test, the study aims to: determine the stability of the product and
efficiency of the suspending agent by measuring the extent of sedimentation

1.5. For the Redispersibility Test, the study aims to: determine whether the product is redispersible or
not since this affects the distribution of active ingredients in the drug product
1.6. For the Test for Viscosity, the study aims to: determine the resistance to flow exhibited by the
product; and ensure its quality, stability and efficiency as viscosity greatly affects product
performance.
1.7. For the Test for pH, the study aims to: determine the pH of the drug product, which affects the
effectiveness of the drug as an antacid.
1.8. For the Organoleptic Evaluation, the study aims to: determine the quality of the suspension through
observing its physical appearance, including its packaging; and confirm if it still remains to be of high
quality or it has visibly deteriorated.
2. SCOPE
2.1. The scope of this procedure is limited to the Aluminum Hydroxide and Magnesium Hydroxide
Suspension manufactured by Drugmakers Laboratories, Inc., which will be subjected under quality
control parameters and specifications. These are to be conducted by and restricted to all the
personnel of Quales Philippines at the Quality Assurance Laboratory of the College of Pharmacy,
University of the Philippines Manila.
2.2. The procedure covers the assay, deliverable volume test, particle size distribution test,
sedimentation volume test, redispersibility, test for viscosity, pH and organoleptic evaluation of the
sample drug.
3. DEFINITIONS
3.1. Assay- test which determines the strength or content of the active pharmaceutical ingredient in
the dosage form; also called Content Test.
3.2. Deliverable volume- volume of dosage form declared on the label which will be delivered by the
product when transferred from the original container; this test also ensures the accuracy and
consistency of manufacturer-supplied products.
3.3. Particle Size Distribution- index indicating what sizes of particles are present in what proportions
in the sample particle group to be measured
3.4. Sedimentation Volume- ratio of the equilibrium volume of the sediment, Vu, to the total volume, Vo
of the suspension; this test gives only a qualitative idea about the sedimentation of the
suspension.
3.5. Redispersibility- measure as to how readily the particles are resuspended after shaking
thoroughly
3.6. Viscosity- an internal property of a fluid that offers resistance to flow.
4. MATERIALS AND EQUIPMENT
4.1. Assay
4.1.1.
4.1.2.
4.1.3.
4.1.4.
4.1.5.

Buret
125 mL Erlenmeyer Flask
Two 50 mL beakers
250 mL beaker
200 mL volumetric flask

4.1.6.
4.1.7.

Filter paper
Dropper

4.2. Deliverable Volume Test

4.2.1. 30 containers of Aluminum Hydroxide and Magnesium Hydroxide Suspension
4.2.2. 10 100-mL graduated cylinders
4.3. Particle Size Distribution Test
4.3.1. Microscope
4.3.2. Glass slides
4.3.3. Cover slips
4.4. Sedimentation Volume Test
4.4.1. 100-ml graduated cylinder
4.5. Redispersibility Test
4.5.1. 100-ml graduated cylinder
4.6. Test for Viscosity
4.6.1. Brookfield Dial Viscometer
4.6.2. 50-mL graduated cylinders
4.7. Test for pH
4.7.1. pH Meter
5. ROLES AND RESPONSIBILITIES
Name
Leigh Don T. Villanueva
Charleen Joyce C. Usacdin
Ann Lorraine U. Te
Maria Lourdes L. Jacinto

Position
Signature
Quality Assurance Head
Quality Assurance Personnel
Quality Control Head
Quality Control
TEST FOR VISCOSITY
Balde, Nikki Francine D.
Quality Control
Reyes, Ton Agustine F.
Quality Control
Asis, Janina Marie A.
Quality Control
pH AND PARTICLE SIZE DISTRIBUTION
Yumol, Regene C.
Quality Control
Demafiles, Shaynne Laurice A.
Quality Control
Maniquis, B. Kim Leileeni D.
Quality Control
Nieva, Kristel Keith N.
Quality Control
ASSAY
Bacungan, Priscilla Nicole T.
Quality Control
Legaspi, Donato D. Jr.
Quality Control
Alcantara, Salve Alessandria B.
Quality Control
Viva, Grace Kristin T.
Quality Control
SEDIMENTATION VOLUME TEST AND ORGANOLEPTIC EVALUATION
Rivera, Darien John Q.
Quality Control
Mappatao, Nikolai Thadues Q.
Quality Control
DELIVERABLE VOLUME AND REDISPERSIBILITY
Magno, Daryl E.
Quality Control
Tabud, Daryl G.
Quality Control
Olayan, Imma Coney P.
Quality Control

6. PROCEDURE AND GUIDELINES

6.1. Aluminum Hydroxide Assay:
6.1.1. Assay Preparation
6.1.1.1. Transfer 26.0 mL of Oral Suspension, previously well shaken in its original
container to a 100 mL beaker.
6.1.1.2. Add 20 mL of water, stir, and slowly add 10 mL of hydrochloric acid.
6.1.1.3. Heat gently, if necessary, to aid solution, cool, and filter into a 200-mL volumetric
flask.
6.1.1.4. Wash the filter with water into the flask, add water to volume, and mix.
6.1.2. Assay Procedure
6.1.2.1. Pipet 10 mL of Assay preparation into a 250-mL in beaker then add 20 mL of
water.
6.1.2.2. Add, in the order named and with continuous stirring, 25.0 mL of 0.05 M Edetate
disodium titrant and 20 mL of acetic acidammonium acetate buffer TS.
6.1.2.3. Cool, add 50 mL of alcohol and 2 mL of dithizone TS, and mix,
6.1.2.4. Titrate with 0.05 M zinc sulfate VS until the color changes from green-violet to rosepink.
6.1.2.5. Perform a blank determination, substituting 10 mL of in the Assay preparation, and
make any necessary correction.
6.1.2.6. Each mL of 0.05 M Edetate disodium titrant consumed is equivalent to 3.900 mg of
Al(OH)3.
6.1.3. Sample Computations:
Aluminum Hydroxide

. () =
1000

=0.05 (25 10)

78 /
11000

=0.0585g Al(OH)3
0.0585

=
10
200
X= 1.1700g of Al(OH)3
1.1700 . 225 ()3
=

5
X= 26.00mL of Oral suspension
Assay Computation
() =

[ ( )] [ ( )]

Convert to equivalent of 5 mL of Oral Suspension

Then compute for % Label Claim
Example:

()3
1000

MEDTA = 0.05 M

Nf EDTA = 1.001

MZnSO4 = 0.05 M

Nf ZnSO4 = 1.002

() =

Volume of EDTA =
25.00 mL
Volume of ZnSO4 =
10.00 mL

MW Al(OH)3 = 78g/mol
F=1

[0.05 1.001 (25.00 1.00)] [0.05 1.002 (10.00 1.00)]

VBlank = 1.00 mL

78/
1 1000

= 1.1704 g / 25 mL
= 0.234 g / 5mL
Compute for the % Labelled Claim

% =

100

% =

0.234
5 100
0.225
5

=104.04%

6.2. Magnesium Hydroxide Assay

6.2.1. Assay Preparation
6.2.1.1. Transfer 26.0 mL of Oral Suspension, previously well shaken in its original
container to a 100 mL beaker.
6.2.1.2. Add 20 mL of water, stir, and slowly add 10 mL of hydrochloric acid.
6.2.1.3. Heat gently, if necessary, to aid solution, cool, and filter into a 200-mL volumetric
flask.
6.2.2. Assay Procedure
6.2.2.1. Pipet 8.00 mL of Assay preparation, into a 400-mL beaker.
6.2.2.2. Add 200 mL of water and 20 mL of triethanolamine, and stir.
6.2.2.3. Add 10 mL of ammonia-ammonium chloride buffer TS and 3 drops of an
eriochrome black indicator solution.
6.2.2.4. Eriochrome black indicator solution is prepared by dissolving 200 mg of eriochrome
black T in a mixture of 15 mL of triethanolamine and 5 mL of dehydrated alcohol,
and mix.
6.2.2.5. Cool the solution to between 3 and 4 by immersion of beaker in an ice bath, then
remove.
6.2.2.6. Titrate with 0.05 M edetate disodium VS to a blue endpoint.
6.2.2.7. Perform a blank determination, substituting 10 mL of water for the Assay
preparation make any necessary correction.
6.2.2.8. Each mL of 0.05 M edetate disodium consumed is equivalent to 2.916 mg of
Mg(OH)2.
6.2.3. Sample Computation
Magnesium Hydroxide
26.00
5
=

200
X= 1.040 g of Mg(OH)2

1.040 0.040 ()2

=
200

X= 8.00mL of Oral suspension
Assay Computation

()2 =

( )
8

58.32 /
1000
200

Convert to equivalent of 5 mL of Oral Suspension

Then compute for % Label Claim
Example:
MEDTA = 0.05 M

Nf EDTA = 1.001

()2 =

Volume of EDTA =
15.00 mL

MW Al(OH)3 = 78g/mol

0.05 (15.00 1.00 )

8

VBlank = 1.00 mL

58.32 /
1000
200

= 1.0206 g / 25 mL
= 0.2041 g / 5mL
Compute for the % Labelled Claim

% =

100

% =

0.2041
5 100
0.200
5

=102.06 %

6.3. Deliverable Volume Test

6.3.1. Obtain not fewer than 30 containers of Aluminum Hydroxide and Magnesium Hydroxide
Suspension.
6.3.2. Shake the contents of 10 containers individually.
6.3.3. Gently pour the contents of each container into separate dry graduated cylinders of a
capacity not exceeding two and half times the volume to be measured and calibrated to
contain. Avoid formation of air bubbles.
6.3.4. Allow each container to drain for a period not to exceed 30 minutes.
6.3.5. Measure the volume of each mixture as it becomes free from bubbles.
6.4. Particle Size Distribution Test
6.4.1. Mount sample on a slide and place on a mechanical stage
6.4.2. Fit a micrometer in the eyepiece of the microscope
6.4.3. Count and measure the particles seen
6.4.4. Create a frequency distribution curve.
6.5. Sedimentation Volume Test

6.5.1.
6.5.2.
6.5.3.
6.5.4.
6.5.5.
6.5.6.

Shake the suspension vigorously, making sure all of the particles are suspended
uniformly.
Immediately pour the suspension into a 100-ml graduated cylinder.
Take note of the total volume (Vo) of the suspension.
Allow the suspension to sit undisturbed for 24 hours.
Then, determine and record the final volume (Vu) of the sediment.
Calculate the sedimentation volume (F) using this formula: = Vu / VO

6.6. Redispersibility Test

6.6.1. Place reconstituted suspension in 100 mL graduated cylinder.
6.6.2. Let suspension stand for 24 hours.
6.6.3. Invert graduated cylinder and count number of inversions required to resuspend
particles.
6.6.3.1.1. Each inversion must be done for 1 second.
6.6.3.1.1.1. Record time required to achieve resuspension.
6.7. Test for Viscosity
6.7.1. Place the sample in a 50-mL graduated cylinder.
6.7.2. Attach the appropriate spindle to the viscometer.
6.7.3. Immerse the spindle into the sample so that its annular groove is at the surface level of
the sample. Ensure that the spindle is in the center of the container opening.
6.7.4.
Make sure to place the spindle guard to protect the torsion spring.
6.7.5.
Place the instrument in its slowest fixed speed.
6.7.6.
Align the pointer to coincide with the zero of the scale.
6.7.7.
Depress the clutch of the instrument and turn the unit on.
6.7.8.
Release slowly the clutch to allow the dial to rotate until the pointer stabilizes at a
fixed
position on the dial.
6.7.9.
Depress the clutch again and turn the unit off, with the pointer clearly visible within
the
dial window.
6.7.10.
Record the reading at which the pointer coincide. Refer to the Factor-Finder
supplied/found with the viscometer for the viscosity of the sample.
6.7.11. Repeat steps 4 to 5 but in the next higher speed.
6.7.12. Continue until the pointer moves more than the maximum reading.
6.7.13. Without letting the system to reform, repeat steps 4 to 5 but this time from the last higher
speed to the lowest speed.
6.7.14. Plot the shear rate (rpm) vs. shear stress (dial reading).
6.7.15. Determine the yield value by multiplying the dial reading to the appropriate factor for the
spindle and speed use, provided with the viscometer.
6.7.16. Sample Computation
Given:
Spindle no. 3, Speed= 0.3
Dial Reading= 2
Factor= 4000
To get viscosity:
Dial Reading x Factor = Viscosity
2 x 4000 = 8000 centipoise (cps)

6.8. Test for pH

6.8.1. Use pH meter to determine the pH of the suspension.
6.9. Organoleptic Evaluation
The suspension is observed for its physical characteristics, including its packaging.
7. ACCEPTANCE CRITERIA
7.1. Assay
It contains the equivalent of not less than 90.0 percent and not more than 110.0 percent of the
labeled amounts of aluminum hydroxide [Al(OH)3] and magnesium hydroxide [Mg(OH)2].
7.2. Deliverable Volume Test
The average volume of liquid obtained from the 10 containers is not less than 100% and the volume
of no container is less than 95% of the volume declared in the labeling. If A, the average volume is
less than 100% of that declared in the labeling, but the volume of no container is less than 95% of
the labeled amount, or if B, the average volume is not less than 100% and the volume of not more
than 1 container is less than 95% but is not less than 90% of the labeled volume, perform the test
on 20 additional containers. The average volume of liquid obtained from the 30 containers is not
less than 100% of the volume declared in the labeling; and the volume of liquid obtained from not
more than 1 of the 30 containers is less than 95%, but not less than 90% of that declared in the
labeling.
7.3. Particle Size Distribution Test
A normal distribution curve must be observed
7.4. Sedimentation Volume Test
The value of F normally lies between 0 to 1 for any pharmaceutical suspension.
7.5. Redispersibility Test
Uniform dispersion; evaluated qualitatively as constant percentage of inversion of the suspension
7.6. Test for Viscosity
The suspension exhibits pseudoplastic behavior.
7.7. Test for pH
pH ranges from 7.0 to 8.6.
7.8. Organoleptic Evaluation
Milky white suspension
8. REFERENCES
8.1. Gennaro, A., 1995. Remington: The Science and Practice of Pharmacy, 19th ed. Mack
Publishing.
8.2. Kulshreshtha, A.K., Singh, O.N., Wall, G.M., 2010. Pharmaceutical Suspensions: From
Formulation Development to Manufacturing. New York: Springer, 53.
8.3. Singh, Y., Sinko, P.J., 2011. Martins Physical Pharmacy and Pharmaceutical Sciences.
Philadelphia: Lippincott Williams & Wilkins, 442-451
8.4. United States Pharmacopoeial Convention Inc., 2011. The United States Pharmacopoeial
Convention 33rd Revision and the National Formulary 28th Edition (e-book) Rockville
Md: USPCI.