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Experiment No.

10

Complexometry

Assay of Alumina and Magnesia Oral Suspension for Aluminum Content, USP 35

I. PRINCIPLE INVOLVED
The assay of Alumina and Magnesia Oral Suspension for aluminum content involves an indirect
titration, which undergoes a complexation reaction. The excess titrant to be used is 0.05M Edetate
disodium VS, and the back titrant is 0.05M Zinc sulfate VS. The indicator to be used is dithizone TS.
The conditions of the titration require being done in a buffered-acidic media of around pH 4-5 since
the endpoint occurs at around pH 4.6 and is indicated by the color transition of green-violet to rose-
pink. A blank determination is to be done as well to correct any errors caused by the indicator.

II. PROCEDURE (USP 35, 2012, p. 2116)


Edetate disodium titrant—Prepare and standardize as directed in the Assay under Ammonium Alum
Assay preparation—Transfer an accurately measured quantity of Oral Suspension, previously well
shaken in its original container, equivalent to about 1200 mg of aluminum hydroxide, to a suitable
beaker. Add 20 mL of water, stir, and slowly add 10 mL of hydrochloric acid. Heat gently, if
necessary, to aid solution, cool, and filter into a 200-mL volumetric flask. Wash the filter with water
into the flask, add water to volume, and mix.
Procedure – Pipet 10 mL of Assay preparation into a 250-mL beaker, add 20 mL of water, then add,
in the order named and with continuous stirring, 25.0 mL of Edetate disodium titrant and 20 mL of
acetic acid–ammonium acetate buffer TS, and heat near the boiling point for 5 minutes. Cool, add 50
mL of alcohol and 2 mL of dithizone TS, and mix. Titrate with 0.05 M zinc sulfate VS until the color
changes from green-violet to rose-pink. Perform a blank determination, substituting 10 mL of water
for the Assay preparation, and make any necessary correction. Each mL of 0.05 M Edetate disodium
titrant consumed is equivalent to 3.900 mg of Al(OH)3.

III. OFFICIAL REQUIREMENT (USP 35, 2012, p. 2115)

Alumina and Magnesia Oral Suspension is a mixture containing aluminum hydroxide [Al(OH)3] and
Magnesium Hydroxide [Mg(OH) 2]. It contains the equivalent of not less than 90.0 % and not more
than 110.0 % of the labelled amounts of aluminum hydroxide & Magnesium Hydroxide. It may
contain a flavoring agent, and may contain suitable antimicrobial agents.

IV. CLEAN UP PROCEDURE

Zinc EDTA & Aluminum EDTA solution – dispose in metal waster container bottle.

V. REASONS FOR IMPORTANT STEPS


(Assay preparation)

Well shaken oral suspension in its original container

- To ensure that the solid content is well dispersed throughout the suspension to acquire accurate
amount of aluminum hydroxide needed for the assay.
Adding 10mL HCl to Aluminum hydroxide prior to the titration

- Aluminum hydroxide is an insoluble white precipitate, but dissolves in the addition of acid due
to the formation of AlCl3 which dissociates Al+3 ions. (Svehla, 1996, p.119)

Heating and Filtering the mixture

- The mixture is heated to aid the dissolution of aluminum, while it is filtered to remove any
undissolved aluminum hydroxide.

(Assay procedure)

***Using 10mL aliquot from the stock solution

- 10mL is to be used since the weighed sample is too large for a titration and is beyond the
capacity of the instruments.

Adding 0.05M Edetate disodium VS

- Disodium salt is preferred due to its characteristics of being non-hygroscopic, solubility in water,
and stability compared to the free acid. (Knevel & DiGangi, 1967, p.147)

Adding Edetate disodium VS in excess


- To ensure that the complexation between the edetate and aluminum ions is complete
- A residual titration is done because aluminum hydroxide will be difficult to complex with EDTA if
done in direct titration.
(Knevel & DiGangi, 1977, p.152)

Buffer solution (Acetic acid & Ammonium acetate) of around pH 4-5


- Acidic conditions inhibit the formation of Mg & EDTA complex which occur at around pH 10,
therefore only allowing aluminum to react with EDTA. (Yang & Tsai, 2006, p. 906)
- Ammonium acetate and Acetic acid buffer solution provides a buffer range of pH 4.75 (pKa of
acetic acid) and pH 9.25 (pKa of ammonium) (Konermann, 2017, p.1827)

Heating mixture near boiling point for 5 minutes


- To ensure complete aluminum edetate complex formation because it can form a stable complex
with EDTA in a slow reaction. (Yang & Tsai, 2006, p. 906)

Adding alcohol
- To act as the solvent for the indicator dithizone TS (Wänninen & Ringbom, 1955, p. 308)

Using Dithizone TS as an indicator


- Gives a sharp endpoint with zinc sulfate, only reacts with excess zinc ions when all of the EDTA
has complexed with zinc. (Hamilton & Simpson, 1964, p. 301)
Using 0.05M Zinc sulfate VS as a back titrant
- Zinc sulfate dissociates into zinc ions which will complex with excess EDTA to form Zinc EDTA
complex which do not interfere with Aluminum EDTA complex. Dithizone TS indicator then
complexes with the excess zinc sulfate which creates a sharp color change of rose pink.
(Knevel & DiGangi, 1967, p. 148)

Performing a Blank determination


- To correct any errors brought by the indicator due to the instability of dithizone TS. (Merck &
Co, 2013)

VI. CHEMICAL EQUATIONS


Al(OH)3↓ + 3HCl  AlCl3 + 3H2O (Svehla, 1996, p.119)

AlCl3 + Na2[C10H14N2O8]  Na[AlC10H14N2O8] +2HCl + NaCl (Beckett & Stenlake, 1988, p. 223)
Factor = 1, because 1:1 mole of aluminum reacting with EDTA ion (Beckett & Stenlake, 1988, p. 206)

ZnSO4 + Na2[C10H14N2O8]  Na[ZnC10H14N2O8] + H2SO4 (Beckett & Stenlake, 1988, p. 221)

VII. PRE-LABORATORY COMPUTATIONS


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VIII. REFERENCES
 Beckett, A. H., Stenlake, J. B. (1988) Practical Pharmaceutical Chemistry (4th Edition). Great
Britain: The Athlone Press.
 Hamilton, L. F., Simpson, S. G. (1964) Quantitative Chemical Analysis (12th Edition). New
York: Macmillan Co
 Merck & Co. (2013) The Merck Index. (15th Edition). Cambridge: The Royal Society of
Chemistry.
 Sciencelab (2005) Aluminum chloride MSDS. Retrieved from
www.sciencelab.com/msds.php?msdsId=9925580
 Svehla, G. (1996) Vogel’s Qualitative Inorganic Analysis. (7th Edition). Essex, England:
Addison Wesley Longman Ltd.
 Toralba, GLP
 United States Pharmacopeial Convention. (2012). The United States Pharmacopeia (35th
Edition) and National Formulary (30th Revision). Rockville, MD: The United States
Pharmacopeial Convention. P. 2115, 2116
 Wänninen E., Ringbom, A. (1955) Complexometric Titration of Aluminum. Analytica Chimica
Acta, 12, 308. Retrieved from https://doi.org/10.1016/S0003-2670(00)87844-7
 Yang, S. Y., Tsai, R. Y. (2006) Complexometric Titration of Aluminum and Magnesium Ions in
Commercial Antacids. Journal of Chemical Education, 83(6), 906. Retrieved from
10.1021/ed083p906