Theophylline and Guaifenesin Capsules
»Theophylline and Guaifenesin Capsules contain not less than 90.0percent and not more than 110.0percent of the labeled amounts of anhydrous theophylline (C7H8N4O2)and guaifenesin (C10H14O4).
Packaging and storage— Preserve in tight containers.
Identification— Transfer a quantity of the contents of the Capsules,equivalent to about 150mg of theophylline,to a separator,and add 15mLof water.To a second separator transfer 15mLof an aqueous Standard solution containing USP Theophylline RSand USP Guaifenesin RScorresponding,proportionately,to the amounts of theophylline and guaifenesin in the Capsules and having a known concentration of about 10mg of theophylline per mL.Treat the contents of each separator as follows.Add 25mLof chloroform,and shake vigorously for 0.5minute.Allow the layers to separate,filter the lower chloroform layer through glass wool,and evaporate the filtrate to dryness.Dissolve the residue in 10mLof chloroform.Apply separately 10µLof each solution so obtained to a thin-layer chromatographic cellulose sheet with fluorescent indicator (see Chromatography á621ñ),allow the spots to dry,and develop the chromatogram in a solvent system consisting of a mixture of methanol and water (95:5)until the solvent front has moved about 10cm above the starting line.Remove the sheet from the developing chamber,mark the solvent front,and allow the solvent to evaporate.Expose the sheet to short-wavelength UVlight:the RFvalues of the spots obtained from the test preparation correspond to those obtained from the Standard solution.
Dissolution á711ñ—
Medium: simulated gastric fluid;900mL.
Apparatus 1: 100rpm.
Time: 45minutes.
Procedure— Determine the amounts of theophylline (C7H8N4O2)and guaifenesin (C10H14O4)dissolved in filtered portions of the solution under test and employing the procedure set forth in the Assay,making any necessary volumetric adjustments,in comparison with Standard solutions having known concentrations of USP Theophylline RSand USP Guaifenesin RSin the same medium.
Tolerances— Not less than 75%(Q)of the labeled amounts of C7H8N4O2and C10H14O4are dissolved in 45minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Assay—
pH6.5buffer solution— Dissolve 1.36g of monobasic potassium phosphate in water to make 1000mL.Carefully adjust with 2.5Nsodium hydroxide to a pHof 6.5,and filter.
Mobile phase— Prepare a degassed solution of pH6.5buffer solutionand methanol (70:30).
Internal standard solution— Dissolve about 400mg of caffeine in 1000mLof a solution of methanol and water (90:10),and mix.
Standard preparation— Dissolve an accurately weighed quantity of USP Theophylline RSin pH6.5buffer solution,and dilute quantitatively with pH6.5buffer solutionto obtain a solution (Solution T)having a known concentration of about 900Jµg per mL,in which Jis the ratio of the labeled amount of theophylline to that of guaifenesin.Transfer about 90mg of USP Guaifenesin RS,accurately weighed,to a 200-mLvolumetric flask,add about 150mLof pH6.5buffer solution,shake to dissolve,dilute with pH6.5buffer solutionto volume,and mix.Pipet 10mLof this solution,10mLof Internal standard solution,and 5mLof Solution Tinto a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix to obtain a Standard preparationhaving known concentrations of about 90µg of guaifenesin and about 90Jµg of theophylline per mL.
Assay preparation— Transfer a number of Capsules,equivalent to about 900mg of guaifenesin,to a 200-mLvolumetric flask,add about 160mLof pH6.5buffer solution,heat to dissolve completely,cool to room temperature,dilute with pH6.5buffer solutionto volume,and mix.Dilute 10.0mLof this solution with pH6.5buffer solutionto 100.0mL.Pipet 10mLof the diluted solution and 10mLof Internal standard solutioninto a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Chromatographic system (seeChromatography á621ñ)— The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1.0mLper minute.Chromatograph six replicate injections of the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation of the ratio of peak responses (peak response of ingredient/peak response of internal standard)is not more than 2.0%for theophylline and not more than 2.5%for guaifenesin.The resolution,R,between theophylline and caffeine is not less than 3.0.
Procedure— Separately inject equal volumes (about 25µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.The relative retention times are about 0.7for theophylline,1.0for caffeine,and 1.5for guaifenesin.Calculate the quantities,in mg,of anhydrous theophylline (C7H8N4O2)and guaifenesin (C10H14O4)in the portion of Capsules taken by the formula:
10C(RU/RS),
in which Cis the concentration,in µg per mL,of the appropriate USP Reference Standard in the Standard preparation,and RUand RSare the ratios of the peak responses of the corresponding analyte to those of caffeine in the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 1901
Phone Number:1-301-816-8379