Loratadine 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

Loratadine Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of loratadine (C₂₂H₂₃ClN₂O₂).

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.

B. The UV spectrum of the major peak of the Sample solution exhibits maxima and minima at the same wavelengths as those of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer: 1.74 g/L of potassium phosphate dibasic in water. Adjust with phosphoric acid to a pH of 7.2.

Solution A: Acetonitrile and methanol (50:50)

Mobile phase: Solution A and Buffer (75:25)

Diluent: Acetonitrile, methanol, 0.05 N hydrochloric acid, and 0.6 M potassium phosphate dibasic (26:26:40:8)

Standard solution: 0.1 mg/mL of USP Loratadine RS in Diluent

Sample solution: Nominally 0.1 mg/mL of loratadine in Diluent, prepared as follows. Transfer NLT 10 Capsules into a suitable volumetric flask. Add Diluent to about 50% of the total flask volume. Sonicate for about 30 min. Dilute with Diluent to volume. Transfer an appropriate volume of this solution into a suitable volumetric flask. Dilute with Diluent to volume. Pass a portion of the solution through a suitable filter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm. For Identi

cation B, use a diode array detector in the range of 200–400 nm.

Column: 4.6-mm × 15-cm; 5-μm packing L1

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 20 μL

Run time: NLT 2 times the retention time of loratadine

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 the labeled amount of loratadine (C₂₂H₂₃ClN₂O₂) in the portion of Capsules taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of loratadine from the Sample solution

r_S = peak response of loratadine from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Perform the test using the conditions under Tier 1. In the presence of cross-linking, repeat the test with new Capsules using the conditions under Tier 2.

Test 1 (RB 1-Jun-2022)

Tier 1

Solution A: 1 g/L of polysorbate 20 in 0.1 N hydrochloric acid, prepared as follows. Mix 8.5 mL of hydrochloric acid in 1 L of water. Add 1g of polysorbate 20.

Medium: Solution A; 900 mL

Apparatus 2: 75 rpm with sinker

Time: 20 min

Tier 2

Solution B: 1 g/L of polysorbate 20 and 1.2 g/L of pepsin in 0.1 N hydrochloric acid, prepared as follows. Mix 8.5 mL of hydrochloric acid in 1 L of water. Add 1.0 g of polysorbate 20 and 1.16 g of pepsin.

Medium: Solution B; 900 mL

Apparatus 2: 75 rpm with sinker

Time: 20 min

Determine the amount of loratadine (C₂₂H₂₃ClN₂O₂) dissolved using the following method.

Mobile phase: Prepare as directed in the Assay.

Standard stock solution: 0.1 mg/mL of USP Loratadine RS, prepared as follows. Transfer an appropriate amount of USP Loratadine RS to a suitable volumetric flask. Add about 20% of the total flask volume of methanol. Sonicate to dissolve. Dilute with Medium to volume.

Standard solution: 0.01 mg/mL of USP Loratadine RS in Medium, from Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6 mm × 25-cm, 5-μm packing L1

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 50 μL

Run time: NLT 2 times the retention time of loratadine

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 the labeled amount of loratadine (C₂₂H₂₃ClN₂O₂) dissolved:

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

r_U = peak response of loratadine from the Sample solution

r_S = peak response of loratadine from the Standard solution

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

L = label claim (mg/Capsule)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of loratadine (C₂₂H₂₃ClN₂O₂) is dissolved.

Test 2

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

Medium: 0.1 N hydrochloric acid containing 0.1% polysorbate 20; 900 mL

Apparatus 2: 75 rpm, with sinkers

Time: 30 min

Buffer: 6.8 g/L of potassium phosphate monobasic in water. Adjust with phosphoric acid to a pH of 2.8.

Mobile phase: Acetonitrile and Buffer (50:50)

Standard solution: 0.011 mg/mL of USP Loratadine RS in Medium. [Note—A few milliliters of acetonitrile may be needed to reduce foaming.]

Sample solution: Pass a portion of solution under test through a suitable filter, discarding at least the first 3 mL.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 15-cm, 5-μm packing L1

Column temperature: 35°

Flow rate: 1 mL/min

Injection volume: 50 μL

Run time: NLT 2 times the retention time of loratadine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.7

Relative standard deviation: NMT 3.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of loratadine (C₂₂H₂₃ClN₂O₂) dissolved:

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

r_U = peak response of loratadine from the Sample solution

r_S = peak response of loratadine from the Standard solution

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

V = volume of Medium, 900 mL

L = label claim (mg/Capsule)

Tolerances: NLT 80% (Q) of the labeled amount of loratadine (C₂₂H₂₃ClN₂O₂) is dissolved. (RB 1-Jun-2022)

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Solution A: 1.36 g/L of potassium phosphate monobasic in water. Adjust with phosphoric acid to a pH of 3.0.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Prepare as directed in the Assay.

Standard stock solution: 1 mg/mL each of USP Loratadine RS and USP Loratadine Related Compound A RS in methanol

Standard solution: 0.01 mg/mL each of USP Loratadine RS and USP Loratadine Related Compound A RS in Diluent, from Standard stock solution

Sensitivity solution: 0.4 μg/mL each of USP Loratadine RS and USP Loratadine Related Compound A RS in Diluent, from Standard solution

Sample solution: Nominally 0.4 mg/mL of loratadine in Diluent, prepared as follows. Transfer NLT 10 Capsules into a suitable volumetric flask. Add Diluent to about 60% of the total flask volume. Sonicate for about 20 min. Allow to cool to room temperature, and dilute with

Diluent to volume. Pass a portion of the solution through a suitable filter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Column temperature: 35°

Flow rate: 1.2 mL/min

Injection volume: 50 μL

System suitability

Samples: Standard solution and Sensitivity solution

[Note—See Table 2 for relative retention times.]

Suitability requirements

Tailing factor: NMT 2.0 for loratadine and loratadine related compound A, Standard solution

Relative standard deviation: NMT 5.0% for loratadine and loratadine related compound A, Standard solution

Signal-to-noise ratio: NLT 10 for loratadine and loratadine related compound A, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of loratadine related compound A from the Sample solution

r_S = peak response of loratadine related compound A from the Standard solution

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

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

Calculate the percentage of any unspecified degradation product in the portion of Capsules taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any unspecified degradation product from the Sample solution

r_S = peak response of loratadine from the Standard solution

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

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

Acceptance criteria: See Table 2.

Table 2

6 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial viable count does not exceed 103cfu/mL, and the total combined yeasts and molds count does not exceed 102cfu/mL. It meets the requirements of the test for the absence of Escherichia coli.

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Store at a temperature between 20°–25°. Protect from freezing.

Add the following:

Labeling: The labeling states the Dissolution test used only if Test 1 is not used. (RB 1-Jun-2022)

USP Reference Standards 〈11〉

USP Loratadine RS

USP Loratadine Related Compound A RS

8-Chloro-5,6-dihydro-11-(piperidin-4-ylidene)-11H-benzo[5,6]cyclohepta[1,2-b]pyridine.