Tacrine Capsules
» Tacrine Capsules contain an amount of Tacrine Hydrochloride equivalent to not less than 90.0 percent and not more than 110.0 percent of the labeled amount of tacrine (C13H14N2).
Packaging and storage— Preserve in well-closed containers.
Identification—
A: Infrared Absorption 197K
Test specimen— Transfer an amount of Capsules, equivalent to about 100 mg of tacrine, to a 250-mL separatory funnel containing 100 mL of water, and mix. Add 2 mL of 1 N sodium hydroxide, and shake. Add 30 mL of 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 105 for 90 minutes. 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 preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution 711
Medium: 0.1 N hydrochloric acid; 900 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Procedure— Determine the amount of C13H14N2 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 240 nm 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 RS in the same Medium.
Tolerances— Not less than 85% (Q) of the labeled amount of C13H14N2 is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Procedure for content uniformity
Standard solution— Dissolve an accurately weighed quantity of USP Tacrine Hydrochloride RS in 0.1 N hydrochloric acid, and dilute quantitatively, and stepwise if necessary, with 0.1 N hydrochloric acid to obtain a solution having a known concentration of about 4.1 µg per mL.
Test solution— Place 1 intact Capsule in a 100-mL volumetric flask, add about 70 mL of 0.1 N hydrochloric acid, and sonicate until the gelatin capsule shell has dissolved completely (about 15 minutes). [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 30 additional minutes, dilute with 0.1 N hydrochloric acid to volume, and mix. Pass a portion of the solution through a suitable filter, and dilute quantitatively with 0.1 N hydrochloric acid to obtain a solution having a concentration of about 4.1 µg 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-mL volumetric flask and prepare as directed for Test solution.
Procedure— Concomitantly determine the absorbances at 240 nm of the Blank, the Standard solution, and the Test solution with 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 L is the labeled quantity, in mg, of tacrine hydrochloride in the Capsule; CS is the concentration, in µg per mL, of USP Tacrine Hydrochloride RS in the Standard solution; CU is 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; 198.27 and 234.73 are the molecular weights of tacrine and tacrine hydrochloride, respectively; and AU and AS are the absorbances obtained from the Test solution and the Standard solution, respectively.
Assay—
0.1 M Triethylamine phosphate solution— Transfer 28 mL of triethylamine to a 2000-mL volumetric flask containing about 1800 mL of water, and mix. Adjust with phosphoric acid to a pH of 3.25, dilute with water to volume, and mix.
Mobile phase— Prepare a filtered and degassed mixture of 0.1 M Triethylamine phosphate solution and methanol (85:15). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed quantity of USP Tacrine Hydrochloride RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 100 µg of tacrine per mL.
Assay preparation— Transfer 10 Capsules to a 1000-mL volumetric flask containing 500 mL of Mobile phase. Sonicate for about 45 minutes 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 300 mL of Mobile phase, shake for 30 minutes on a mechanical shaker, dilute with Mobile phase to volume, and mix. Pass an aliquot of this solution through an appropriate filter presaturated with the solution, and dilute, if necessary, with Mobile phase to obtain a solution containing about 100 µg of tacrine per mL.
Chromatographic system (see Chromatography 621)— 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 2.5 mL per minute. Initially, the detector is maintained at a wavelength of 240 nm. At 7.0 minutes, the wavelength is changed to 260 nm. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 3500 theoretical 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 30 µL) of the Standard preparation and the Assay preparation into 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 C is the concentration, in mg per mL, of USP Tacrine Hydrochloride RS in the Standard preparation; 198.27 and 234.73 are the molecular weights of tacrine and tacrine hydrochloride, respectively; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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Topic/Question Contact Expert Committee
Monograph Elena Gonikberg, Ph.D.
Senior Scientist
1-301-816-8251
(MDGRE05) Monograph Development-Gastrointestinal Renal and Endocrine
Reference Standards Lili Wang, Technical Services Scientist
1-301-816-8129
RSTech@usp.org
711 Margareth R.C. Marques, Ph.D.
Senior Scientist
1-301-816-8106
(BPC05) Biopharmaceutics05
USP32–NF27 Page 3648