Test 1: If the product complies with this test,the labeling indicates that it meets USPDrug Release Test 1.

pH1.2buffer solution— Dissolve 2.0g of sodium chloride in water,add 7.0mLof hydrochloric acid,dilute with water to 1liter,and mix.

pH6.8buffer solution— Dissolve 21.72g of anhydrous dibasic sodium phosphate and 4.94g of citric acid monohydrate in water,dilute with water to 1liter,and mix.

Media— Proceed as directed under Method Bfor Delayed-release(Enteric-coated)Articles,using 900mLof pH1.2buffer solutionduring the Acid stage,run for 1.5hours,and use the acceptance criteria given under Tolerances.For the Buffer stage,use 900mLof pH6.8buffer solution,run for the time specified,and use the acceptance criteria given under Tolerances.

Apparatus 1: 100rpm.

Times: 1.5hours,4hours,8hours,14hours,24hours.

Procedure— Using filtered portions of the solution under test,diluted if necessary,determine the amount of C16H21NO2·HCl dissolved,using UVabsorbances at the wavelength of maximum absorbance at about 320nm,with respect to a baseline drawn from 355nm through 340nm,by comparison with a Standard solution in water having a known concentration of USP Propranolol Hydrochloride RS.

Tolerances— The percentages of the labeled amount of C16H21NO2·HCl dissolved at the times specified conform to Acceptance Table 1.

Test 2: If the product complies with this test,the labeling indicates that it meets USPDrug Release Test 2.

pH1.2buffer solution— Dissolve 2.0g of sodium chloride in water,add 7.0mLof hydrochloric acid,dilute with water to 1liter,and mix.

pH7.5buffer solution— Dissolve 6.8g of monobasic potassium phosphate and 1.6g of sodium hydroxide in 900mLof water,adjust with 1Nsodium hydroxide to a pHof 7.5,dilute with water to 1liter,and mix.

Media— Proceed as directed under Method Bfor Delayed-release(Enteric-coated)Articles—General Drug Release Standard,using 900mLof pH1.2buffer solutionduring the Acid stage,run for 1hour,and use the acceptance criteria given under Tolerances.For the Buffer stage,use 900mLof pH7.5buffer solution,run for the time specified,and use the acceptance criteria given under Tolerances.

Apparatus 1: 50rpm.

Times: 1hour,3hours,6hours,12hours.

Procedure— Using filtered portions of the solution under test,diluted if necessary,determine the amount of C16H21NO2·HCl dissolved,using UVabsorbances at the wavelength of maximum absorbance at about 320nm,with respect to a baseline drawn from 355nm through 340nm,by comparison with a Standard solution in water having a known concentration of USP Propranolol Hydrochloride RS.

Tolerances— The percentages of the labeled amount of C16H21NO2·HCl dissolved at the times specified conform to Acceptance Table 1.

Procedure for content uniformity— Transfer the contents of 1Capsule to a 100-mLvolumetric flask,add about 70mLof methanol,swirl occasionally for 30minutes,and sonicate for about 1minute,and then swirl occasionally for an additional 30minutes.Dilute with methanol to volume,mix,and centrifuge a portion of the solution.Dilute an accurately measured volume of the clear solution quantitatively with methanol to obtain a solution containing about 40µg of propranolol hydrochloride per mL.Concomitantly determine the absorbances of this solution and a Standard solution of USP Propranolol Hydrochloride RSin methanol having a known concentration of about 40µg per mL,in 1-cm cells at the wavelength of maximum absorbance at about 290nm,with a suitable spectrophotometer,using methanol as the blank.Calculate the quantity,in mg,of C16H21NO2·HCl in the Capsule taken by the formula: in which Lis the labeled quantity,in mg,of propranolol hydrochloride in the Capsule,Cis the concentration,in µg per mL,of USP Propranolol Hydrochloride RSin the Standard solution,Dis the concentration,in µg per mL,of the solution from the Capsule,based on the labeled quantity per Capsule and the extent of dilution,and AUand ASare the absorbances of the solution from the Capsule and the Standard solution,respectively.

Phosphate buffer— Dissolve 13.6g of monobasic potassium phosphate in 2liters of water,and mix.Filter the solution through a 0.5-µm or finer porosity filter before use.

Mobile phase— Prepare a suitable degassed mixture of Phosphate bufferand acetonitrile (650:350).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Diluting solvent— Mix 650mLof water with 350mLof acetonitrile.

Standard preparation— Dissolve an accurately weighed quantity of USP Propranolol Hydrochloride RSin methanol,and dilute quantitatively and stepwise with methanol to obtain a solution having a known concentration of about 200µg per mL.Transfer 5.0mLof this solution to a 50.0-mLvolumetric flask,add Diluting solventto volume,and mix.

Assay preparation— Transfer the contents of 10Capsules,accurately counted,to a 500-mLvolumetric flask.Add 300mLof methanol,and swirl by mechanical means for 2hours.Allow to stand for about 16hours,then sonicate for one-half hour,and swirl for one-half hour.Dilute with methanol to volume,mix,and centrifuge a portion of the solution.Dilute an accurately measured volume of the clear solution quantitatively with Diluting solventto obtain a solution having a concentration of about 20µg of propranolol hydrochloride per mL.

Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 220-nm detector and a 4-mm ×15-cm column that contains 5-µm packing L1.The flow rate is about 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency determined from the analyte peak is not less than 1000theoretical plates,the tailing factor for the analyte peak is not more than 3,and the relative standard deviation for replicate injections is not more than 2%.

Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.The retention time of propranolol is about 5to 9minutes.Calculate the quantity,in mg,of C16H21NO2·HCl in each Capsule taken by the formula: in which Lis the labeled quantity,in mg,of propranolol hydrochloride in each Capsule,Cis the concentration,in µg per mL,of USP Propranolol Hydrochloride RSin the Standard preparation,Dis the concentration,in µg of propranolol hydrochloride per mL,of the Assay preparation,based on the labeled quantity per Capsule,the number of Capsules taken,and the extent of dilution,and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.