Fexofenadine Hydrochloride Tablets
DEFINITION
Fexofenadine Hydrochloride Tablets contain NLT 95.0% and NMT 105.0% of the labeled amount of fexofenadine hydrochloride (C32H39NO4·HCl).
IDENTIFICATION
•  A. Infrared Absorption 197K
Standard solution:  Transfer 60 mg of USP Fexofenadine Hydrochloride RS to a suitable capped tube and add 10 mL of a mixture of acetonitrile and methanol (10:1).
Sample solution:  Transfer an equivalent to 60 mg of fexofenadine hydrochloride, from a sufficient number of weighed and finely powdered Tablets, to a suitable capped tube, and add 10 mL of a mixture of acetonitrile and methanol (10:1).
Analysis:  Shake or mix the Standard solution and Sample solution on a vortex mixer for 1–2 min to disperse the sample. Allow the solution to stand for 10 min, or centrifuge for 2–3 min. Pass the liquid into a 50-mL beaker using a 0.45-µm polytetrafluoroethlyene syringe filter. Evaporate the solvent until about 0.5 mL remains, using a stream of nitrogen with gentle heating (do not exceed 75). Add 5 mL of water and 5 drops of dilute hydrochloric acid, and stir to induce precipitation. Chill in an ice bath for 30 min. Filter the solution through a 10- to 15-µm sintered-glass crucible. Dry the precipitate in an air oven for 1 h at 105 oven for 1 h at 105. Prepare a bromide dispersion from the residue.
Acceptance criteria:  The IR absorption spectrum of the potassium bromide dispersion of the residue from the sample exhibits maxima only at the same wavelengths as that of a potassium bromide dispersion from the Standard.
•  B. The retention time of the major peak in the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
•  Procedure
Solution A:  Glacial acetic acid and water (17:983). Dilute 100 mL of this solution with water to 1 L.
Solution B:  Dilute 15 mL of a solution containing acetonitrile and triethylamine (1:1) with Solution A to 1 L. Adjust with phosphoric acid to a pH of 5.25.
Diluent:  Acetonitrile and Solution A (3:1)
Mobile phase:  Acetonitrile and Solution B (9:16)
Standard stock solution:  0.25 mg/mL of USP Fexofenadine Hydrochloride RS in Diluent
Standard solution:  0.015 mg/mL from the Standard stock solution in Mobile phase
Sample stock solution:  Transfer a sufficient number of whole Tablets (NLT 10) to a suitable volumetric flask, add Solution A (equivalent to 20% of the total flask volume), and shake by mechanical means at a high speed for 30 min or until the Tablets are fully disintegrated and finely dispersed. Add acetonitrile (equivalent to 80% of the total flask volume), and shake by mechanical means for 60 min. Dilute with Diluent to volume. Pass a portion of this solution through a polytetrafluoroethylene filter having a 0.45-µm or finer pore size, and use the filtrate. Dilute, if necessary, with Diluent to obtain a solution containing an equivalent to 1.2 mg/mL of fexofenadine hydrochloride.
Sample solution:  0.018 mg/mL from the Sample stock solution in Mobile phase
Chromatographic system 
Mode:  LC
Detector:  UV 220 nm
Column:  4.6-mm × 25-cm; 5-µm packing L11
Column temperature:  35
Flow rate:  1.5 mL/min
Injection size:  20 µL
System suitability 
Sample:  Standard solution
Suitability requirements 
Tailing factor:  NMT 2.0
Relative standard deviation:  NMT 2.0%
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of C32H39NO4·HCl in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== concentration of USP Fexofenadine Hydrochloride RS in the Standard solution (mg/mL)
CU== nominal concentration of fexofenadine hydrochloride in the Sample solution (mg/mL)
Acceptance criteria:  95.0%–105.0%
PERFORMANCE TESTS
•  Dissolution 711
Test 1 
Medium:  0.001 N hydrochloric acid; 900 mL, deaerated
Apparatus 2:  50 rpm
Time:  10 and 30 min
Determine the percentages of the labeled amount of C32H39NO4·HCl dissolved by using the following method.
Solution A:  1.0 g of monobasic sodium phosphate, 0.5 g of sodium perchlorate, and 0.3 mL of concentrated phosphoric acid in 300 mL of water
Mobile phase:  Acetonitrile and Solution A (7:3)
Standard solution:  USP Fexofenadine Hydrochloride RS in Medium to obtain a solution having a known concentration similar to that expected for the solution under test. [Note—A small amount of methanol, not exceeding 0.5% of the total volume, can be used to dissolve fexofenadine hydrochloride. ]
System suitability solution:  0.44 mg/mL of USP Fexofenadine Related Compound A RS in water. Transfer 1.0 mL of this solution into a vial, and add 40 mL of the Standard solution. [Note—A small amount of acetic acid, not exceeding 5% of the total volume, can be used to dissolve fexofenadine related compound A. ]
Sample solution:  Pass portions of the solution under test through a glass fiber filter having a 0.45-µm pore size.
Chromatographic system  
Mode:  LC
Detector:  UV 220 nm
Column:  4.6-mm × 10-cm; packing L1
Flow rate:  1 mL/min
Injection size:  2–3 µg column load of fexofenadine hydrochloride
System suitability 
Samples:  Standard solution and System suitability solution
Suitability requirements 
Resolution:  NLT 2.0 between fexofenadine and fexofenadine related compound A, System suitability solution
Relative standard deviation:  NMT 2.0%, Standard solution
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of C32H39NO4·HCl dissolved in the portion of Tablets taken:
Result = (rU/rS) × (CS/L) × D × V × 100
rU== peak area from the Sample solution
rS== peak area from the Standard solution
CS== concentration of USP Fexofenadine Hydrochloride RS in the Standard solution (mg/mL)
L== Tablet label claim (mg)
D== dilution factor of the Sample solution
V== volume of Medium, 900 mL
Tolerances:  NLT 60% (Q) of the labeled amount of C32H39NO4·HCl is dissolved in 10 min; NLT 80% (Q) of the labeled amount of C32H39NO4·HCl is dissolved in 30 min.
Test 2 
If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.
Medium:  0.001 N hydrochloric acid; 900 mL
Apparatus 2:  50 rpm. Use paddles and shafts coated with Teflon.
Time:  30 min
Determine the percentages of the labeled amount of C32H39NO4·HCl dissolved by using the following method.
Solution A:  7 mg/mL of ammonium acetate in water. Adjust with glacial acetic acid to a pH of 4.0 ± 0.05.
Mobile phase:  Acetonitrile and Solution A (2:3)
Standard solution 1:  Transfer 20 mg of USP Fexofenadine Hydrochloride RS to a 100-mL volumetric flask. Add 3.0 mL of methanol, and mix. Dilute with Medium to volume.
Standard solution 2:  Transfer 15.0 mL of Standard solution 1 to a 50-mL volumetric flask. Dilute with Medium to volume.
Standard solution 3:  Transfer 7.5 mL of Standard solution 1 to a 50-mL volumetric flask. Dilute with Medium to volume.
Sample solution:  Pass portions of the solution under test through a suitable filter of 0.45-µm pore size.
Chromatographic system 
Mode:  LC
Detector:  UV 259 nm
Column:  4.6-mm × 15-cm; packing L11
Flow rate:  1.5 mL/min
Injection size:  10 µL for Standard solution 1 and 30 µL for Standard solutions 2 and 3
System suitability 
Sample:  Any of the Standard solutions
Suitability requirements 
Tailing factor:  NMT 2.0
Relative standard deviation:  NMT 2.0%
Analysis 
Samples:  Standard solutions 1, 2, and 3 and the Sample solution
Calculate the percentage of C32H39NO4·HCl dissolved in the portion of Tablets taken:
Result = (rU/rS) × (CS/L) × V × 100
rU== peak area from the Sample solution
rS== peak area from the Standard solution
CS== concentration of the appropriate Standard solution (mg/mL)
V== volume of Medium, 900 mL
L== Tablet label claim (mg)
Tolerances:  NLT 75% (Q) of the labeled amount of C32H39NO4·HCl is dissolved.
Test 3 
If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 3.
Medium:  0.001 N hydrochloric acid; 900 mL for Tablets labeled to contain 30 mg or 60 mg, and 1800 mL for Tablets labeled to contain 180 mg
Apparatus 2:  50 rpm
Time:  45 min
Buffer solution:  6.64 g/L of monobasic sodium phosphate monohydrate and 0.84 g/L of sodium perchlorate monohydrate in water. Add 4 mL/L of triethylamine. Adjust with phosphoric acid to a pH of 2.3 ± 0.1.
Mobile phase:  Buffer solution and acetonitrile (65:35)
Standard stock solution:  0.5 mg/mL of USP Fexofenadine Hydrochloride RS in Mobile phase. This solution is stable for 3.5 months under refrigeration or for 18 days at room temperature.
Standard solution:  Dilute the Standard stock solution with Medium to obtain a final concentration of 0.07 mg/mL of USP Fexofenadine Hydrochloride RS. This solution is stable for 8 days under refrigeration or for 24 h at room temperature.
Sample solution:  Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Chromatographic system 
Mode:  LC
Detector:  UV 220 nm
Column:  4.6-mm × 10-cm; 5-µm packing L1
Column temperature:  40
Flow rate:  2.5 mL/min
Injection size:  20 µL
System suitability 
Sample:  Standard solution
Suitability requirements 
Tailing fator:  NMT 2.0
Column efficiency:  NLT 1000 theroretical plates
Relative standard deviation:  NMT 2.0%
Calculate the percentage of fexofenadine hydrochloride dissolved in the portion of Tablets taken:
Result = (rU/rS) × (CS/L) × V × 100
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== concentration of the Standard solution (mg/mL)
L== Tablet label claim (mg)
V== volume of Medium, 900 or 1800 mL
Tolerances:  NLT 75% (Q) of the labeled amount of fexofenadine hydrochloride is dissolved.
•  Uniformity of Dosage Units 905: Meet the requirements
IMPURITIES
Organic Impurities 
•  Procedure
Solution A, Solution B, Diluent, Mobile phase, Standard stock solution, Sample stock solution, and Sample solution:  Prepare as directed in the Assay.
Standard solution:  0.015 mg/mL of fexofenadine hydrochloride and 0.0045 mg/mL of fexofenadine related compound A from Quantitative limit solution and the Standard stock solution in Mobile phase
System suitability stock solution:  Dilute 4.0 mL of the Standard stock solution with Mobile phase to 100 mL.
System suitability solution:  Dilute 6.0 mL of the System suitability stock solution with Mobile phase to 100 mL.
Quantitative limit solution:  0.05 mg/mL of USP Fexofenadine Related Compound A RS in Diluent
Chromatographic system 
Mode:  LC
Detector:  UV 220 nm
Column:  4.6-mm × 25-cm; 5-µm packing L11
Column temperature:  35
Flow rate:  1.5 mL/min
Injection size:  20 µL
System suitability 
Samples:  Standard solution and System suitability solution
[Note—For the relative retention times, see Impurity Table 1. ]
Suitability requirements 
Resolution:  NLT 7 between fexofenadine and fexofenadine related compound A, Standard solution
Tailing factor:  NMT 2.0, Standard solution
Relative standard deviation:  NMT 6%, System suitability solution; NMT 2.0% and NMT 3.0% for fexofenadine and fexofenadine related compound A, Standard solution
Analysis 
Samples:  Standard solution, Sample stock solution, and Sample solution
Calculate the percentage of fexofenadine related compound A in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak area of fexofenadine related compound A in the Sample stock solution
rS== peak area of fexofenadine related compound A in the Standard solution
CS== concentration of fexofenadine related compound A in the Standard solution (mg/mL)
CU== concentration of Fexofenadine hydrochloride in the Sample stock solution
Calculate the percentage of the decarboxylated degradant [(±)-4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl]-isopropylbenzene] in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
rU== peak area of the decarboxylated degradant in the Sample stock solution
rS== peak area of fexofenadine in the Standard solution
CS== concentration of USP Fexofenadine Hydrochloride RS in the Standard solution (mg/mL)
CU== concentration of fexofenadine hydrochloride in the Sample stock solution
F== relative response factor (see Impurity Table 1)
Calculate the percentage of any other impurities in the portion of Tablets taken:
Result = rU/(F × rS + rT) × 100
rU== peak area for each individual unknown impurity in the Sample stock solution
F== difference in concentration between the Sample stock solution and the Sample solution, 66.7
rS== peak area response for fexofenadine in the Sample solution
rT== sum of the peak areas of all unknown impurities in the Sample stock solution
[Note—Disregard any peak below 0.05%. ]
Acceptance criteria 
Individual impurities:  See Impurity Table 1.
Total impurities:  NMT 0.5%
Impurity Table 1
Name Relative
Retention
Time
Relative
Response
Factor
Acceptance
Criteria,
NMT (%)
Fexofenadine related compound A 1.6 0.4
Decarboxylated degradant 6.7 1.1 0.15
Fexofenadine 1.0
Any individual other impurity 1.0 0.2
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in well-closed containers, and store at controlled room temperature.
•  Labeling: When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.
•  USP Reference Standards 11
USP Fexofenadine Hydrochloride RS Click to View Structure
USP Fexofenadine Related Compound A RS
Benzeneacetic acid, 4-[1-oxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-,-dimethyl.
    C32H37NO4        499.65
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