Fexofenadine Hydrochloride Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Fexofenadine Hydrochloride Tablets contain NLT 93.0% and NMT 107.0% of the labeled amount of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl).

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 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 polytetra fluoroethlyene 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.

3 ASSAY

3.1 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 suffcient 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 (suffcient to fill the flask to 80% of its volume), and shake by mechanical means for 60 min. Dilute with Diluent to volume. Pass a portion of this solution through a polytetra fluoroethylene fllter 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

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

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 volume: 20 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₃₂H₃₉NO₄ · HCl in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_S /C_U )× 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Fexofenadine Hydrochloride RS in the Standard solution (mg/mL)

C_U = nominal concentration of fexofenadine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 93.0%–107.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

4.1 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 glacial 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 ber filter having a 0.45-μm pore size.

4.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 10-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 2–3 μg column load of fexofenadine hydrochloride

4.1.2 System suitability

Samples: Standard solution and System suitability solution

4.1.3 Suitability requirements

Resolution: NLT 2.0 between fexofenadine and fexofenadine related compound A, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

4.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₃₂H₃₉NO₄ · HCl dissolved in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_S /L) × D × V × 100

r_U = peak area from the Sample solution

r_S = peak area from the Standard solution

C_S = 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.

4.2 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.

4.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 259 nm

Column: 4.6-mm × 15-cm; packing L11

Flow rate: 1.5 mL/min

Injection volume: 10 μL for Standard solution 1 and 30 μL for Standard solutions 2 and 3

4.2.2 System suitability

Sample: Any of the Standard solutions

4.2.3 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

4.2.4 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 = (r_U /r_S ) × (C_S /L) × V × 100

r_U = peak area from the Sample solution

r_S = peak area from the Standard solution

C_S = 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.

4.3 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 180mg

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.

4.3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

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 volume: 20 μL

4.3.2 System suitability

Sample: Standard solution

4.3.3 Suitability requirements

Tailing factor: NMT 2.0

Column efficiency: NLT 1000 theoretical plates

Relative standard deviation: NMT 2.0%

Calculate the percentage of fexofenadine hydrochloride dissolved in the portion of Tablets taken:

Result = (r_U /r_S ) × (C_S /L) × V × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = 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.

4.4 Test 4

If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 4.

Medium: 0.001 N hydrochloric acid; 900 mL, degassed

Apparatus 2: 75 rpm

Time: 15 min

Buffer solution: 6.64 g/L of monobasic sodium phosphate monohydrate and 0.84 g/L of sodium perchlorate in water. Adjust with phosphoric acid to a pH of 2.0.

Mobile phase: Acetonitrile, Buffer solution, and triethylamine (50: 50: 0.3)

Standard stock solution: 0.55 mg/mL of USP Fexofenadine Hydrochloride RS in 0.01 N hydrochloric acid

Standard solution: Dilute the Standard stock solution with Medium to obtain a final concentration of 0.22 mg/mL of USP Fexofenadine Hydrochloride RS. Pass a portion of the solution through a suitable filter of 0.45-μm pore size.

Sample solution: Pass a portion of the solution under test through a suitable filter.

4.4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 25-cm; 5-μm packing L11

Column temperature: 25°

Flow rate: 1.5 mL/min

Injection volume: 20 μL

Run time: NLT 2.7 times the retention time of fexofenadine

4.4.2 System suitability

Sample: Standard solution

4.5 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

4.5.1 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) dissolved in the portion of Tablets taken:

Result = (r_U /r_S ) × C_S × V × (1/L) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCll) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Change to read:

Organic Impurities

5.1 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

5.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

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 volume: 20 μL

5.3 System suitability

Samples: Standard solution and System suitability solution

[Note—For the relative retention times, see Impurity Table 1.]

5.4 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

5.5 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 = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak area of fexofenadine related compound A in the Sample stock solution

r_S = peak area of fexofenadine related compound A in the Standard solution

C_S = concentration of fexofenadine related compound A in the Standard solution (mg/mL)

C_U = 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 = (r_U /r_S ) × (C_S /C_U) × (1/F) × 100

r_U = peak area of the decarboxylated degradant in the Sample stock solution

r_S = peak area of fexofenadine in the Standard solution

C_S = concentration of USP Fexofenadine Hydrochloride RS in the Standard solution (mg/mL)

C_U = 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 = r_U /(F × r_S + r_T) × 100

r_U = 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

r_S = peak area response for fexofenadine in the Sample solution

r_T = sum of the peak areas of all unknown impurities in the Sample stock solution

[Note-Disregard any peak below 0.05%.]

5.6 Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: NMT 1.3 (RB 1-May-2024)

Impurity Table 1

6 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

USP Fexofenadine Related Compound A RS

2-(4-{4-[4-(Hydroxydiphenylmethyl)piperidin-1-yl]butanoyl}phenyl)-2-methylpropanoic acid;

Also known as Benzeneacetic acid, 4-[1-oxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-α,α-dimethyl.

C₃₂ H₃₇ NO₄ 499.65