Alumina, Magnesia, and Simethicone Oral Suspension
» Alumina, Magnesia, and Simethicone Oral Suspension contains the equivalent of not less than 90.0 percent and not more than 115.0 percent of the labeled amounts of aluminum hydroxide [Al(OH)3] and magnesium hydroxide [Mg(OH)2], and an amount of polydimethylsiloxane [(CH3)2SiO]n that is not less than 85.0 percent and not more than 115.0 percent of the labeled amount of simethicone.
Packaging and storage Preserve in tight containers, and avoid freezing.
Labeling Oral Suspension may be labeled to state the aluminum hydroxide content in terms of the equivalent amount of dried aluminum hydroxide gel, on the basis that each mg of dried gel is equivalent to 0.765 mg of Al(OH)3. Label it to state the sodium content if it is greater than 1 mg per mL.
USP Reference standards 11
Cell: 0.5 mm.
Solution: prepared as directed in the Assay for polydimethylsiloxane.
B: To a solution of 5 g in 10 mL of 3 N hydrochloric acid add 5 drops of methyl red TS, heat to boiling, add 6 N ammonium hydroxide until the color of the solution just changes to deep yellow, then continue boiling for 2 minutes, and filter: the filtrate so obtained responds to the tests for Magnesium 191.
C: Wash the precipitate obtained in Identification test B with hot ammonium chloride solution (1 in 50), and dissolve the precipitate in hydrochloric acid. Divide this solution into two portions: the dropwise addition of 6 N ammonium hydroxide to one portion yields a gelatinous white precipitate, which does not dissolve in an excess of 6 N ammonium hydroxide. The dropwise addition of 1 N sodium hydroxide to the other portion yields a gelatinous white precipitate, which dissolves in an excess of 1 N sodium hydroxide, leaving some turbidity.
Microbial enumeration tests 61 and Tests for specified microorganisms 62 Its total aerobic microbial count does not exceed 100 cfu per mL, and it meets the requirements of the test for absence of Escherichia coli.
Acid-neutralizing capacity 301 The acid consumed by the minimum single dose recommended in the labeling is not less than 5 mEq, and not less than the number of mEq calculated by the formula:
0.55(0.0385A) + 0.8(0.0343 M)in which 0.0385 and 0.0343 are the theoretical acid-neutralizing capacities, in mEq, of Al(OH)3 and Mg(OH)2, respectively, and A and M are the quantities, in mg, of Al(OH)3 and Mg(OH)2 in the specimen tested, based on the labeled quantities.
pH 791: between 7.0 and 8.6.
Potassium chloride solution Prepare a solution of potassium chloride in water containing 38 mg per mL.
Sodium chloride stock solution Dissolve a suitable quantity of sodium chloride, previously dried at 105 for 2 hours and accurately weighed, in water, and dilute quantitatively and stepwise with water to obtain a solution containing 25.42 µg per mL (10 µg of sodium per mL).
Standard preparations On the day of use, transfer 4.0 mL of 1 N hydrochloric acid and 10.0 mL of Potassium chloride solution to each of two 100-mL volumetric flasks. To the respective flasks add 5.0 mL and 10.0 mL of Sodium chloride stock solution. Dilute with water to volume, and mix. These solutions contain about 0.5 µg and 1.0 µg of sodium per mL, respectively.
Test preparation Transfer 5.0 mL of Oral Suspension, previously well-shaken in its original container, to a 100-mL volumetric flask, add 50 mL of 1 N hydrochloric acid, boil for 15 minutes, cool to room temperature, dilute with water to volume, and mix. Filter, discarding the first few mL of the filtrate. Transfer 5.0 mL of the filtrate to a 100-mL volumetric flask containing 10.0 mL of Potassium chloride solution, dilute with water to volume, and mix.
Procedure Concomitantly determine the absorbances of the Standard preparations and the Test preparation at the sodium emission line at 589.0 nm with a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light-scattering 851) equipped with a sodium hollow-cathode lamp and an airacetylene flame, using as a blank a solution prepared by pipeting 4 mL of 1 N hydrochloric acid and 10.0 mL of Potassium chloride solution into a 100-mL volumetric flask, diluting with water to volume, and mixing. Plot the absorbances of the Standard preparations versus concentrations, in µg per mL, of sodium and draw a straight line between the plotted points. From the graph so obtained, determine the concentration, C, in µg per mL, of sodium in the Test preparation. Calculate the quantity, in mg, of sodium in each mL of Oral Suspension taken by the formula:
Assay for aluminum hydroxide
Assay preparation Transfer an accurately measured volume of Oral Suspension, previously well-shaken in its original container, equivalent to about 800 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 the 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 temperature 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 making any necessary correction. Each mL of 0.05 M Edetate disodium titrant consumed is equivalent to 3.900 mg of Al(OH)3.
Assay for magnesium hydroxide
Assay preparation Prepare as directed in the Assay for aluminum hydroxide.
Procedure Pipet a volume of the Assay preparation, equivalent to about 40 mg of magnesium hydroxide, into a 400-mL beaker, add 200 mL of water and 20 mL of triethanolamine, and stir. Add 10 mL of ammonia-ammonium chloride buffer TS and 3 drops of an eriochrome black indicator solution 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. Cool the solution to between 3 and 4 by immersion of the beaker in an ice bath, then remove, and titrate with 0.05 M edetate disodium VS to a blue endpoint. Perform a blank determination, substituting water for the Assay preparation, and make any necessary correction. Each mL of 0.05 M edetate disodium consumed is equivalent to 2.916 mg of Mg(OH)2.
Assay for polydimethylsiloxane Transfer an accurately measured volume of Oral Suspension, equivalent to about 50 mg of simethicone, to a suitable round, narrow-mouth, screw-capped, 120-mL bottle, add 40 mL of 0.1 N sodium hydroxide, and swirl to disperse. Add 25.0 mL of toluene, close the bottle securely with a cap having an inert liner, and shake for 15 minutes, accurately timed, on a reciprocating shaker (e.g., about 200 oscillations per minute and a stroke of 38 ± 2 mm). Transfer the mixture to a 125-mL separator. Remove about 5 mL of the upper, organic layer to a screw-capped, 15-mL test tube containing 0.5 g of anhydrous sodium sulfate. Close the tube with a screw-cap having an inert liner, agitate vigorously, and centrifuge the mixture until a clear supernatant (Assay preparation) is obtained. Prepare a Standard preparation similarly, except to dissolve about 50 mg of USP Polydimethylsiloxane RS, accurately weighed, in 25.0 mL of toluene, add 40 mL of 0.1 N sodium hydroxide, and add a volume of water equal to that of the specimen of Oral Suspension taken. Prepare a blank by mixing 10 mL of toluene with 0.5 g of anhydrous sodium sulfate and centrifuging to obtain a clear supernatant. Concomitantly determine the absorbances of the solutions in 0.5-mm cells at the wavelength of maximum absorbance at about 7.9 µm, with a suitable IR spectrophotometer, using the blank to set the instrument. Calculate the quantity, in mg, of [(CH3)2SiO]n in each mL of the Oral Suspension taken by the formula:
(W / V)(AU / AS)in which W is the weight, in mg, of USP Polydimethylsiloxane RS used in preparing the Standard preparation; V is the volume, in mL, of Oral Suspension taken; and AU and AS are the absorbances of the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 2120Pharmacopeial Forum: Volume No. 33(5) Page 871