» Aminophylline Tablets contain an amount of aminophylline equivalent to not less than 93.0 percent and not more than 107.0 percent of the labeled amount of anhydrous theophylline (C7H8N4O2).
[noteThe ammoniacal odor present in the vapor space above Aminophylline Tablets is often quite strong, especially when bottles having suitably tight closures are newly opened. This is due to ethylenediamine vapor pressure build-up, a natural condition in the case of aminophylline. ]
Packaging and storage Preserve in tight containers.
Labeling Label the Tablets to state the content of anhydrous theophylline.
USP Reference standards 11
A: Macerate a quantity of Tablets, equivalent to about 500 mg of aminophylline, with 25 mL of water, and filter: the filtrate is alkaline to litmus. To the filtrate add 1 mL of 3 N hydrochloric acid, stir, and chill, if necessary, to precipitate the theophylline. Filter, and retain the filtrate, free from washings. Wash the crystals on the filter with small quantities of ice-cold water, and dry at 105 for 1 hour: the theophylline so obtained responds to Identification test B under Aminophylline, and when recrystallized from water and dried at 105 for 1 hour, melts between 270 and 274.
B: The filtrate obtained in Identification test A responds to Identification test C under Aminophylline.
for uncoated or plain coated tablets
Medium: water; 900 mL.
Apparatus 2: 50 rpm.
Time: 45 minutes.
Procedure Determine the amount of anhydrous theophylline (C7H8N4O2) dissolved from UV absorbances at the wavelength of maximum absorbance at about 269 nm on filtered portions of the solution under test, suitably diluted with water, if necessary, in comparison with a Standard solution having a known concentration of USP Theophylline RS in the same Medium.
Tolerances Not less than 75% (Q) of the labeled amount of C7H8N4O2 is dissolved in 45 minutes.
Uniformity of dosage units 905: meet the requirements.
Procedure for content uniformity Place 1 Tablet in a 250-mL volumetric flask, add about 200 mL of water, and shake by mechanical means until disintegration is complete. Add water to volume, and mix. Filter a portion of the mixture, discarding the first 20 mL of the filtrate. Concomitantly determine the absorbances of this solution, quantitatively diluted, if necessary, and a Standard solution of USP Theophylline RS having a known concentration of about 10 µg per mL, in 1-cm cells at the wavelength of maximum absorbance at about 269 nm, with a suitable spectrophotometer, using water as the blank. Calculate the quantity, in mg, of anhydrous theophylline (C7H8N4O2) in the Tablet taken by the formula:
(TC/D)(AU / AS)in which T is the labeled quantity, in mg, of anhydrous theophylline in the Tablet, D is the concentration, in µg per mL, of theophylline in the solution from the Tablet, based on the labeled quantity per Tablet and the extent of dilution, C is the concentration, in µg per mL, of USP Theophylline RS in the Standard solution, and AU and AS are the absorbances of the solution from the Tablet and the Standard solution, respectively.
Ethylenediamine content Accurately weigh a portion of the powdered Tablets prepared in the Assay, equivalent to about 350 mg of aminophylline, transfer to a 100-mL conical flask, add 20 mL of water, and digest at 50, with frequent shaking, for 30 minutes. Cool, filter into a 250-mL conical flask, and wash with water until the last washing is neutral to litmus. To the combined filtrate and washings add methyl orange TS, and titrate with 0.1 N hydrochloric acid VS. Each mL of 0.1 N hydrochloric acid is equivalent to 3.005 mg of C2H8N2. The Tablets contain between 140 mg and 190 mg of ethylenediamine (C2H8N2) per g of C7H8N4O2 found in the Assay.
Assay Weigh and finely powder not fewer than 20 Tablets. Transfer a portion of the powder, equivalent to about 2 g of aminophylline, to a 200-mL volumetric flask with the aid of a mixture of 50 mL of water and 15 mL of 6 N ammonium hydroxide, and allow to stand for 30 minutes with frequent shaking, warming to about 50, if necessary, to dissolve the aminophylline. Cool the mixture to room temperature if it has been warmed, add water to volume, and mix. Centrifuge about 50 mL of the mixture, and pipet a portion of the clear supernatant, equivalent to about 250 mg of aminophylline, into a 250-mL conical flask, and dilute with water, if necessary, to make about 40 mL. Add 8 mL of 6 N ammonium hydroxide and 20.0 mL of 0.1 N silver nitrate VS, mix, heat to boiling, and continue boiling for 15 minutes. Cool to between 5 and 10 for 20 minutes, then filter, preferably through a filtering crucible under reduced pressure, and wash the precipitate with three 10-mL portions of water. Acidify the combined filtrate and washings with nitric acid, and add an additional 3 mL of the acid. Cool, add 2 mL of ferric ammonium sulfate TS, and titrate the excess silver nitrate with 0.1 N ammonium thiocyanate VS. Each mL of 0.1 N silver nitrate is equivalent to 18.02 mg of C7H8N4O2.
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USP35NF30 Page 2176Pharmacopeial Forum: Volume No. 27(4) Page 2701