Tacrine Capsules
»Tacrine Capsules contain an amount of Tacrine Hydrochloride equivalent to not less than 90.0percent and not more than 110.0percent of the labeled amount of tacrine (C13H14N2).
Packaging and storage— Preserve in well-closed containers.
Identification—
A: Infrared Absorption á197Kñ—
Test specimen— Transfer an amount of Capsules,equivalent to about 100mg of tacrine,to a 250-mLseparatory funnel containing 100mLof water,and mix.Add 2mLof 1Nsodium hydroxide,and shake.Add 30mLof ether,and shake.Allow the layers to separate,transfer the top ether layer to a beaker,and evaporate in a hood under a stream of nitrogen.Allow the solid to air-dry,and then dry at 105for 90minutes.Prepare a mixture of about 0.5%to 1.0%of the isolated solid in potassium bromide.
B: The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.
Dissolution á711ñ—
Medium: 0.1Nhydrochloric acid;900mL.
Apparatus 2: 50rpm.
Time: 30minutes.
Procedure— Determine the amount of C13H14N2dissolved by employing UVabsorption at the wavelength of maximum absorbance at about 240nm on filtered portions of the solution under test,suitably diluted with Dissolution Medium,in comparison with a Standard solution having a known concentration of USP Tacrine Hydrochloride RSin the same Medium.
Tolerances— Not less than 85%(Q)of the labeled amount of C13H14N2is dissolved in 30minutes.
Uniformity of dosage units á905ñ: meet the requirements.
PROCEDUREFOR CONTENT UNIFORMITY—
Standard solution— Dissolve an accurately weighed quantity of USP Tacrine Hydrochloride RSin 0.1Nhydrochloric acid,and dilute quantitatively,and stepwise if necessary,with 0.1Nhydrochloric acid to obtain a solution having a known concentration of about 4.1µg per mL.
Test solution— Place 1intact Capsule in a 100-mLvolumetric flask,add about 70mLof 0.1Nhydrochloric acid,and sonicate until the gelatin capsule shell has dissolved completely (about 15minutes).[NOTE—Periodically swirl the flask during the sonication to loosen the Capsule from the bottom of the flask and to dissolve a floating Capsule.]Shake mechanically for about 30additional minutes,dilute with 0.1Nhydrochloric acid to volume,and mix.Pass a portion of the solution through a suitable filter,and dilute quantitatively with 0.1Nhydrochloric acid to obtain a solution having a concentration of about 4.1µg of tacrine hydrochloride per mL.[NOTE—Do not use nylon filters.]Immediately prior to removing an aliquot for analysis,mix the solution vigorously.
Blank— Place an empty Capsule of each Capsule strength into a separate 100-mLvolumetric flask and prepare as directed for Test solution.
Procedure— Concomitantly determine the absorbances at 240nm of the Blank,the Standard solution,and the Test solutionwith a suitable spectrophotometer.Calculate the quantity,in mg,of tacrine (C13H14N2)in the Capsule taken by the formula:
1000L(CS/CU)(198.27/234.73)(AU/AS),
in which Lis the labeled quantity,in mg,of tacrine hydrochloride in the Capsule;CSis the concentration,in µg per mL,of USP Tacrine Hydrochloride RSin the Standard solution;CUis the concentration,in µg per mL,of tacrine hydrochloride in the Test solution,based on the labeled quantity per Capsule and the extent of dilution;198.27and 234.73are the molecular weights of tacrine and tacrine hydrochloride,respectively;and AUand ASare the absorbances obtained from the Test solutionand the Standard solution,respectively.
Assay—
0.1M Triethylamine phosphate solution— Transfer 28mLof triethylamine to a 2000-mLvolumetric flask containing about 1800mLof water,and mix.Adjust with phosphoric acid to a pHof 3.25,dilute with water to volume,and mix.
Mobile phase— Prepare a filtered and degassed mixture of 0.1M Triethylamine phosphate solutionand methanol (85:15).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Dissolve an accurately weighed quantity of USP Tacrine Hydrochloride RSin Mobile phase,and dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having a known concentration of about 100µg of tacrine per mL.
Assay preparation— Transfer 10Capsules to a 1000-mLvolumetric flask containing 500mLof Mobile phase.Sonicate for about 45minutes until the gelatin capsule shells have dissolved.Periodically swirl the flask during sonication to loosen any Capsules sticking to the bottom of the flask and to dissolve floating Capsules.Add an additional 300mLof Mobile phase,shake for 30minutes on a mechanical shaker,dilute with Mobile phaseto volume,and mix.Pass an aliquot of this solution through an appropriate filter presaturated with the solution,and dilute,if necessary,with Mobile phaseto obtain a solution containing about 100µg of tacrine per mL.
Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a variable wavelength detector and a 4.6-mm ×15-cm column that contains 5-µm packing L1.The flow rate is about 2.5mLper minute.Initially,the detector is maintained at a wavelength of 240nm.At 7.0minutes,the wavelength is changed to 260nm.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency is not less than 3500theoretical plates;the tailing factor is not more than 2.0;and the relative standard deviation for replicate injections is not more than 1.0%.
Procedure— Separately inject equal volumes (about 30µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the quantity,in mg,of tacrine (C13H14N2)in the portion of Capsules taken by the formula:
1000C(198.27/234.73)(rU/rS),
in which Cis the concentration,in mg per mL,of USP Tacrine Hydrochloride RSin the Standard preparation;198.27and 234.73are the molecular weights of tacrine and tacrine hydrochloride,respectively;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Elena Gonikberg,Ph.D.,Scientist
Expert Committee:(PA4)Pharmaceutical Analysis 4
USP28–NF23Page 1845
Phone Number:1-301-816-8251