Aminophylline Suppositories
»Aminophylline Suppositories contain an amount of aminophylline equivalent to not less than 90.0percent and not more than 110.0percent of the labeled amount of anhydrous theophylline (C7H8N4O2).
Packaging and storage—
Preserve in well-closed containers,in a cold place.
Labeling—
Label the Suppositories to state the content of anhydrous theophylline.
Identification—
A:
Evaporate to about one-half its volume on a steam bath a portion,equivalent to about 500mg of aminophylline,of the water solution prepared in the Assay.Adjust with 1Nsodium hydroxide to a pHof 7.0,chill,and filter the crystals of theophylline.Save the filtrate,free from the washings,for use in Identificationtest B:the crystals,after being washed with small portions of ice-cold water and dried at 105
for 1hour,melt between 270and 274,and respond to Identificationtest Bunder Aminophylline.
for 1hour,melt between 270and 274,and respond to Identificationtest Bunder Aminophylline.
Ethylenediamine content—
Accurately weigh a portion of the stirred,congealed mass of the Suppositories used for the Assay,equivalent to about 500mg of aminophylline,and place in a 500-mLconical flask.Add 150mLof a mixture of equal volumes of alcohol and ether,and warm gently under reflux for 30minutes,with occasional swirling.Cool to room temperature,and titrate with 0.1Nhydrochloric acid VS,using a glass-modified calomel electrode system (replace the saturated potassium chloride solution of the calomel electrode with methanol saturated with lithium chloride).Each mLof 0.1Nhydrochloric acid is equivalent to 3.005mg of C2H8N2.The Suppositories contain between 152mg and 190mg of ethylenediamine (C2H8N2)per g of C7H8N4O2found in the Assay.
Assay—
Tare a small dish and a glass rod,place in the dish not less than 5Suppositories,and heat on a steam bath until melted.Mix the melt by stirring it with the rod,cool while stirring,and weigh.Weigh accurately a portion of the mass,equivalent to about 1g of aminophylline,place it in a beaker,add 60mLof hot water and 3mLof nitric acid,and heat on a steam bath for 15minutes with frequent stirring.Cool,transfer to a separator with the aid of 40mLof ether,shake well,and allow to separate,using a few mLof alcohol,if necessary,to bring about separation of any emulsion that has formed.Draw the water layer into a 100-mLvolumetric flask,wash the ether with two 15-mLportions of water,adding the washings to the volumetric flask,dilute with water to volume,and mix.Transfer an accurately measured portion of the solution,equivalent to about 250mg of aminophylline,to a 250-mLconical flask,add 10mLof 6Nammonium hydroxide and about 20mLof 0.1Nsilver nitrate VS,and heat on a steam bath for 15minutes.Cool to between 5and 10for 20minutes,then filter,preferably through a filtering crucible of fine porosity under reduced pressure,and wash the precipitate with small portions of water until the last washing gives not more than a faint opalescence with hydrochloric acid.Dissolve the precipitate by pouring over it small volumes of warm 2Nnitric acid,receiving the solution in a conical flask.Wash the filtering crucible a few times with warm water acidified with nitric acid,receiving the washings in the same flask.Cool,add 2mLof ferric ammonium sulfate TS,and titrate with 0.1Nammonium thiocyanate VS.Each mLof 0.1Nammonium thiocyanate is equivalent to 18.02mg of theophylline (C7H8N4O2).
and 10for 20minutes,then filter,preferably through a filtering crucible of fine porosity under reduced pressure,and wash the precipitate with small portions of water until the last washing gives not more than a faint opalescence with hydrochloric acid.Dissolve the precipitate by pouring over it small volumes of warm 2Nnitric acid,receiving the solution in a conical flask.Wash the filtering crucible a few times with warm water acidified with nitric acid,receiving the washings in the same flask.Cool,add 2mLof ferric ammonium sulfate TS,and titrate with 0.1Nammonium thiocyanate VS.Each mLof 0.1Nammonium thiocyanate is equivalent to 18.02mg of theophylline (C7H8N4O2).
Auxiliary Information—
Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 130
Phone Number:1-301-816-8379