Aminophylline Tablets
»Aminophylline Tablets contain an amount of aminophylline equivalent to not less than 93.0percent and not more than 107.0percent of the labeled amount of anhydrous theophylline (C7H8N4O2).
NOTE—The 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.
Identification—
A:
Macerate a quantity of Tablets,equivalent to about 500mg of aminophylline,with 25mLof water,and filter:the filtrate is alkaline to litmus.To the filtrate add 1mLof 3Nhydrochloric 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 1hour:the theophylline so obtained responds to Identificationtest Bunder Aminophylline,and when recrystallized from water and dried at 105for 1hour,melts between 270and 274.
for 1hour:the theophylline so obtained responds to Identificationtest Bunder Aminophylline,and when recrystallized from water and dried at 105for 1hour,melts between 270and 274.
B:
The filtrate obtained in Identificationtest Aresponds to Identificationtest Cunder Aminophylline.
Dissolution á711ñ—
FOR UNCOATED OR PLAIN COATED TABLETS—
Medium:
water;900mL.
Apparatus 2:
50rpm.
Time:
45minutes.
Procedure—
Determine the amount of anhydrous theophylline (C7H8N4O2)dissolved from UVabsorbances at the wavelength of maximum absorbance at about 269nm 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 RSin the same Medium.
Tolerances—
Not less than 75%(Q)of the labeled amount of C7H8N4O2is dissolved in 45minutes.
Uniformity of dosage units á905ñ:
meet the requirements.
Procedure for content uniformity—
Place 1Tablet in a 250-mLvolumetric flask,add about 200mLof 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 20mLof the filtrate.Concomitantly determine the absorbances of this solution,quantitatively diluted,if necessary,and a Standard solution of USP Theophylline RShaving a known concentration of about 10µg per mL,in 1-cm cells at the wavelength of maximum absorbance at about 269nm,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 Tis the labeled quantity,in mg,of anhydrous theophylline in the Tablet,Dis 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,Cis the concentration,in µg per mL,of USP Theophylline RSin the Standard solution,and AUand ASare 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 350mg of aminophylline,transfer to a 100-mLconical flask,add 20mLof water,and digest at 50,with frequent shaking,for 30minutes.Cool,filter into a 250-mLconical 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 0.1Nhydrochloric acid VS.Each mLof 0.1Nhydrochloric acid is equivalent to 3.005mg of C2H8N2.The Tablets contain between 140mg and 190mg of ethylenediamine (C2H8N2)per g of C7H8N4O2found in the Assay.
,with frequent shaking,for 30minutes.Cool,filter into a 250-mLconical 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 0.1Nhydrochloric acid VS.Each mLof 0.1Nhydrochloric acid is equivalent to 3.005mg of C2H8N2.The Tablets contain between 140mg and 190mg of ethylenediamine (C2H8N2)per g of C7H8N4O2found in the Assay.
Assay—
Weigh and finely powder not fewer than 20Tablets.Transfer a portion of the powder,equivalent to about 2g of aminophylline,to a 200-mLvolumetric flask with the aid of a mixture of 50mLof water and 15mLof 6Nammonium hydroxide,and allow to stand for 30minutes 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 50mLof the mixture,and pipet a portion of the clear supernatant,equivalent to about 250mg of aminophylline,into a 250-mLconical flask,and dilute with water,if necessary,to make about 40mL.Add 8mLof 6Nammonium hydroxide and 20.0mLof 0.1Nsilver nitrate VS,mix,heat to boiling,and continue boiling for 15minutes.Cool to between 5and 10for 20minutes,then filter,preferably through a filtering crucible under reduced pressure,and wash the precipitate with three 10-mLportions of water.Acidify the combined filtrate and washings with nitric acid,and add an additional 3mLof the acid.Cool,add 2mLof ferric ammonium sulfate TS,and titrate the excess silver nitrate with 0.1Nammonium thiocyanate VS.Each mLof 0.1Nsilver nitrate is equivalent to 18.02mg of C7H8N4O2.
,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 50mLof the mixture,and pipet a portion of the clear supernatant,equivalent to about 250mg of aminophylline,into a 250-mLconical flask,and dilute with water,if necessary,to make about 40mL.Add 8mLof 6Nammonium hydroxide and 20.0mLof 0.1Nsilver nitrate VS,mix,heat to boiling,and continue boiling for 15minutes.Cool to between 5and 10for 20minutes,then filter,preferably through a filtering crucible under reduced pressure,and wash the precipitate with three 10-mLportions of water.Acidify the combined filtrate and washings with nitric acid,and add an additional 3mLof the acid.Cool,add 2mLof ferric ammonium sulfate TS,and titrate the excess silver nitrate with 0.1Nammonium thiocyanate VS.Each mLof 0.1Nsilver nitrate is equivalent to 18.02mg of C7H8N4O2.
Auxiliary Information—
Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 131
Pharmacopeial Forum:Volume No.27(4)Page 2701
Phone Number:1-301-816-8379