Fexofenadine Hydrochloride Capsules

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 Capsules contain NLT 93.0% and NMT 105.0% of the labeled amount of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

Change to read:

B. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

Sample solution: Empty an equivalent of 60 mg of fexofenadine hydrochloride, from the contents of several Capsules, into a suitable capped tube. Add 10 mL of a mixture of acetonitrile and methanol (10:1), and shake until the sample is dispersed. Allow to settle. Decant, filter, and collect the supernatant in a suitable beaker. Evaporate the solvent to near dryness by using a stream of nitrogen and with gentle heating from an appropriate source (steam, low-temperature hot plate). While still warm, add 5 mL of water and 5 drops of diluted hydrochloric acid, and stir to induce precipitation. Chill in an ice bath for about 30 min. Pass through a 10- to 15-μm filtering crucible with fritted disk. Dry the precipitate in an air oven for 1 h at 105°.

Acceptance criteria: Meet the requirements

3 ASSAY

3.1 Procedure

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

Diluent: Acetonitrile and Buffer (1:1)

Mobile phase: Acetonitrile and Buffer (7:13). Add 3 mL/L of triethylamine.

Standard solution: 0.06 mg/mL of USP Fexofenadine Hydrochloride RS and 0.005 mg/mL of USP Fexofenadine Related Compound A RS in

3.2 Mobile phase

Sample stock solution: Remove, as completely as possible, the contents of NLT 20 Capsules, mix the combined contents, and finely powder by using a mortar and pestle. Transfer a portion of the powder, equivalent to about 50 mg of fexofenadine hydrochloride, to a 50-mL volumetric flask. Add 40 mL of Diluent, and shake by mechanical means for 60 min. Sonicate for about 2 min. Allow to cool to room temperature, and dilute with Diluent to volume.

Sample solution: Transfer 3.0 mL of the Sample stock solution to a 50-mL volumetric flask, and dilute with Mobile phase to volume.

3.3 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 25-cm; packing L11

Flow rate: 1.5 mL/min

Injection volume: 20 μL

3.4 System suitability

Sample: Standard solution

3.5 Suitability requirements

Resolution: NLT 10 between fexofenadine and fexofenadine related compound A

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0% and 3.0% for fexofenadine and fexofenadine related compound A, respectively

3.6 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) in the portion of Capsules taken:

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

r_U = peak response from the Sample solution

r_S = peak response of fexofenadine 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%–105.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

Test 1

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 15 and 45 min

Buffer: 1.0 g of monobasic sodium phosphate, 0.5 g of sodium perchlorate, and 0.3 mL of phosphoric acid in 300 mL of water

Mobile phase: Acetonitrile and Buffer (7:3)

System suitability stock solution: 0.44 mg/mL of USP Fexofenadine Related Compound A RS in water. [Note—A small amount of glacial acetic acid, not to exceed 5% of the total volume, may be used if necessary to dissolve USP Fexofenadine Related Compound A RS.]

System suitability solution: Prepare a solution of USP Fexofenadine Hydrochloride RS in the System suitability stock solution containing 0.01 mg/mL of USP Fexofenadine Related Compound A RS and 0.06 mg/mL of USP Fexofenadine Hydrochloride RS. Standard solution: 0.07 mg/mL of USP Fexofenadine Hydrochloride RS in water. [Note—A small amount of methanol, not to exceed 0.5% of the total volume, may be used if necessary to dissolve USP Fexofenadine Hydrochloride RS.]

Sample solution: Filtered portions of the solution under test

4.2 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: 50 μL

4.3 System suitability

Samples: System suitability solution and Standard solution

4.4 Suitability requirements

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

Relative standard deviation: NMT 2.0%, Standard solution

4.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) dissolved.

Tolerances: NLT 50% (Q) of the labeled amount of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) is dissolved in 15 min; NLT 75% (Q) of the labeled amount of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) is dissolved in 45 min.

Test 2: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.

Medium, Apparatus, Buffer, Mobile phase, System suitability stock solution, System suitability solution, Chromatographic system, and

Analysis: Proceed as directed for Test 1.

Time: 45 min

Tolerances: NLT 75% (Q) of the labeled amount of fexofenadine hydrochloride (C₃₂H₃₉NO₄ · HCl) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

5.1 Organic Impurities

Buffer: 6.64 mg/mL of monobasic sodium phosphate and 0.84 mg/mL of sodium perchlorate in water. Adjust with phosphoric acid to a pH of 2.0.

Diluent: Acetonitrile and Buffer (1:1)

Mobile phase: Acetonitrile and Buffer (7:13). Add 3 mL/L of triethylamine

Standard solution: 0.06 mg/mL of USP Fexofenadine Hydrochloride RS and 0.005 mg/mL of USP Fexofenadine Related Compound A RS in

5.2 Mobile phase

Sample solution: Use the Sample stock solution as prepared in the Assay.

Reference solution: 0.06 mg/mL of fexofenadine hydrochloride in Mobile phase from the Sample solution

5.3 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 25-cm; packing L11

Flow rate: 1.5 mL/min

Injection volume: 20 μL

5.4 System suitability

Sample: Standard solution

5.5 Suitability requirements

Resolution: NLT 10 between fexofenadine and fexofenadine related compound A

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0% and 3.0% for fexofenadine and fexofenadine related compound A, respectively

5.6 Analysis

Samples: Standard solution, Sample solution, and Reference solution

Calculate the percentage of fexofenadine related compound A in the portion of Capsules taken:

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

r_U = peak response for fexofenadine related compound A from the Sample solution

r_S = peak response for fexofenadine related compound A from the Standard solution

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

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

Calculate the percentage of decarboxylated degradant [(±)-4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl]-isopropylbenzene], with a relative retention time of 3.2, in the portion of Capsules taken:

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

r_U = peak response of the decarboxylated degradant from the Sample solution

r_S = peak response of fexofenadine from the Standard solution

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

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

F = response factor for the decarboxylated degradant relative to fexofenadine, 1.1

Calculate the percentage of other impurities in the portion of Capsules taken:

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

r_U = peak response for any other impurity from the Sample solution

r_S = peak response of fexofenadine from the Reference solution

C_S = concentration of fexofenadine in the Reference solution (mg/mL)

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

Acceptance criteria: See Table 1.

Table 1

^a Benzeneacetic acid, 4-[1-oxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-α,α-dimethyl.

^b (±)-4-[1-Hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl]-isopropylbenzene.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. 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.

C₃₂H₃₇NO_{​​​​​​​4} 499.65