Propoxyphene Hydrochloride Capsules
»Propoxyphene Hydrochloride Capsules contain not less than 92.5percent and not more than 107.5percent of the labeled amount of C22H29NO2·HCl.
Packaging and storage— Preserve in tight containers.
Identification— Transfer an accurately weighed quantity of Capsule contents remaining from the preparation of the Assay preparationin the Assay,equivalent to about 320mg of propoxyphene hydrochloride,to a 100-mLvolumetric flask.Add 20mLof acetone,and sonicate for about 1minute.Dilute the solution with water to volume,and mix.Allow to stand until the excipients have settled,usually about 15to 20minutes.Transfer 40.0mLof this solution to a 125-mLseparator containing 20mLof sodium carbonate solution (1in 10),and swirl the mixture for 3minutes.Add 25.0mLof chloroform,insert the stopper,and shake the mixture by mechanical means for 1hour.Filter the chloroform extract through a layer of anhydrous sodium sulfate into a suitable beaker.Prepare a Standard solution as follows.Transfer about 125mg of USP Propoxyphene Hydrochloride RS,accurately weighed,to a 125-mLseparator containing 8mLof acetone,32mLof water,and 20mLof sodium carbonate solution (1in 10),and swirl the mixture for 3minutes.Proceed as directed for the test solution,beginning with “Add 25.0mLof chloroform.”Use the chloroform solutions obtained from the Capsule contents and from the USP Propoxyphene Hydrochloride RSfor the following tests.
A: The IRabsorption spectrum of the chloroform solution of the contents of Capsules,concentrated if necessary by evaporating a portion on a steam bath with the aid of a current of air to about one-fifth of its volume,exhibits maxima only at the same wavelengths as that of a similar preparation of USP Propoxyphene Hydrochloride RS.
B: Transfer 20.0mLof the test solution and 20.0mLof the Standard solution to separate beakers,and evaporate on a steam bath with the aid of a current of air to about 5mL.Remove the beakers from the steam bath,and continue evaporation with the aid of a current of air until the chloroform is completely evaporated.Add 5.0mLof 0.1Nhydrochloric acid to each,and dissolve the residue.Using the solution obtained from the test solution,determine the specific rotation (see Optical Rotation á781ñ),in which c,the concentration of propoxyphene hydrochloride per 100mLof solution,is calculated as follows:
0.0064(WU/WT)A,
in which WUis the weight,in mg,of the portion of Capsule contents taken,WTis the average weight,in mg,of the contents of each Capsule,and Ais the quantity,in mg,of propoxyphene hydrochloride per Capsule,as obtained in the Assay.Using the solution obtained from the Standard solution,determine the specific rotation,c,being calculated by multiplying the weight,in mg,of USP Propoxyphene Hydrochloride RStaken by 0.016.The specific rotation obtained from the solution from the test solution is not less than 95.0%of that obtained from the solution from the Standard solution.
C: The chromatogram of the Assay preparationobtained as directed in the Assayexhibits a major peak for propoxyphene hydrochloride,the retention time of which corresponds to that exhibited in the chromatogram of the Standard preparationobtained as directed in the Assay.
Dissolution á711ñ—
Medium:pH4.5acetate buffer ,prepared as directed in the test for Dissolutionunder Propoxyphene Hydrochloride,Aspirin,and Caffeine Capsules;500mL.
Apparatus 1: 100rpm.
Time: 60minutes.
Procedure— Proceed as directed in the Assayusing a filtered portion of the solution under test diluted with Diluent,and a Standard solution having an accurately known concentration of USP Propoxyphene Hydrochloride RSin Diluent.Calculate the amount of propoxyphene hydrochloride dissolved.
Tolerances— Not less than 85%(Q)of the labeled amount of C22H29NO2·HCl is dissolved in 60minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Assay—
Phosphate buffer— Dissolve 6.8g of monobasic potassium phosphate in about 900mLof water.Add 2.0mLof triethylamine,mix,and adjust by the addition of phosphoric acid to a pHof 3.0±0.1.Dilute with water to 1liter,and mix.
Diluent— Prepare a mixture of water and acetonitrile (3:2).
Mobile phase— Prepare a filtered and degassed mixture of Phosphate bufferand acetonitrile (3:2).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Dissolve an accurately weighed quantity of USP Propoxyphene Hydrochloride RSin Diluentwith the aid of sonication to obtain a solution having a known concentration of about 325µg per mL.Transfer 2.0mLof this solution to a 100-mLvolumetric flask,dilute with Diluentto volume,and mix to obtain a Standard preparationhaving a known concentration of about 6.5µg per mL.
Assay preparation— Remove,as completely as possible,the contents of not less than 20Capsules.Weigh the contents,and determine the average weight per capsule.Mix the combined contents,and transfer an accurately weighed quantity of the powder,equivalent to about 65mg of propoxyphene hydrochloride,to a 200-mLvolumetric flask.Add about 50mLof Diluent,sonicate for 5minutes,and shake by mechanical means for 15minutes.Dilute with Diluentto volume,mix,and filter,discarding the first 20mLof the filtrate.Transfer 2.0mLof the filtrate to a 100-mLvolumetric flask,dilute with Diluentto volume,and mix.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm ×3.3-cm column that contains 3-µm packing L1that is base-deactivated.Precondition the column for at least 30minutes with Mobile phase.The flow rate is about 1mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the tailing factor for the propoxyphene hydrochloride peak is not more than 2,and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the peak responses for the major peaks.Calculate the quantity,in mg,of C22H29NO2·HCl in the portion of Capsules taken by the formula:
10C(rU/rS),
in which Cis the concentration,in µg per mL,of USP Propoxyphene Hydrochloride RSin the Standard preparation,and rUand rSare the propoxyphene hydrochloride peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Daniel K.Bempong,Ph.D.,Scientist
Expert Committee:(PA2)Pharmaceutical Analysis 2
USP28–NF23Page 1652
Phone Number:1-301-816-8143