Loratadine Orally Disintegrating 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

Loratadine Orally Disintegrating Tablets contain NLT 95.0% and NMT 105.0% 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.

Add the following:

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in Assay, Procedure 1 or Assay, Procedure 2.2S (USP41)

3 ASSAY

[Note—Matrix effects have been observed that affect the extraction of loratadine. Depending on the composition of the Tablet, use Assay,

Procedure 1 or Assay, Procedure 2.]

Change to read:

Procedure 1

Buffer: 2.72 g/L of monobasic potassium phosphate in water. Adjust with 5 N sodium hydroxide solution to a pH of 6.50 ± 0.05, and filter.

Mobile phase: Acetonitrile and Buffer (70:30)

Diluent: Acetonitrile and Buffer (40:60)

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

Sample solution: Transfer 10 Tablets into a 500-mL volumetric flask, add 400 mL of acetonitrile, and stir for 10 min. Sonicate the solution for 10 min, and stir for another 10 min. Dilute with acetonitrile to volume, and mix. Dilute an aliquot of the resulting solution with Diluent to obtain a solution that has a concentration of about 0.1 mg/mL, based on the label claim. Pass a portion of this solution through a polyvinylidene fluoride (PVDF) filter of 0.45-μm pore size, and discard the first 5 mL of filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm. For Identification B, use a diode array detector in the range of 210–400 nm. 2S (USP41)

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

Flow rate: 1.0 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 3000 theoretical plates

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) 2S (USP41) in the portion of Tablets 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: 95.0%–105.0%

Change to read:

Procedure 2

Buffer: 2.28 g/L of dibasic potassium phosphate trihydrate

Mobile phase: Methanol, acetonitrile, and Buffer (6:6:7), adjusted with 10% phosphoric acid to an apparent pH of 7.2

Diluent: Methanol and water (1:1)

System suitability solution: 0.8 μg/mL each of USP Loratadine Related Compound A RS, USP Loratadine Related Compound B RS, and USP

Loratadine Related Compound C RS in Diluent

Standard solution: 0.4 mg/mL of USP Loratadine RS in Diluent. [Note—The solution may be sonicated for 5 min to aid in dissolution.]

Sample solution: Transfer a quantity of Tablets into a 250-mL volumetric flask so that the final concentration is 0.4 mg/mL, based on the label claim. Add 50 mL of water, and sonicate, if necessary, to disperse the Tablets. Add 50 mL of methanol, and shake to dissolve. Dilute with Diluent to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm. For Identification B, use a diode array detector in the range of 210–400 nm.2S (USP41)

Column: 4.6-mm × 15-cm; 5-μm packing L7

Flow rate: 1.0 mL/min

Injection volume: 15 μL for the Standard solution and Sample solution; 50 μL for the System suitability solution

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for loratadine related compound A, loratadine related compound C, loratadine related compound B, and loratadine are about 0.26, 0.31, 0.42, and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.2 between loratadine related compound A and loratadine related compound C; NLT 1.2 between loratadine related compound C and loratadine related compound B, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of loratadine (C₂₂H₂₃ClN₂O₂) 2S (USP41) in the portion of Tablets 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: 95.0%–105.0%

4 PERFORMANCE TESTS

Disintegration 〈701〉

Test 1

Stage 1: All 6 Tablets completely disintegrate in 1 min.

Stage 2: NLT 16 of 18 Tablets completely disintegrate in 1 min.

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

Analysis: Place a stainless steel wire clip on each Tablet to prevent the Tablet from floating.

Acceptance criteria: NMT 30 s

Change to read:

Dissolution 〈711〉

Medium: Simulated gastric fluid without enzymes; 900 mL, deaerated

Apparatus 1: 50 rpm

Time: 6 min

Standard solution: Prepare a solution of USP Loratadine RS in Medium at a concentration similar to that expected in the Sample solution.

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

Instrumental conditions

Mode: UV

Analytical wavelength: 278 nm

Cell: 1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

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

Result = (A_U/A_S) × C_S × (V/L) × 100

A_U = absorbance from the Sample solution

A_S = absorbance from the Standard solution

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

V = volume of Medium, 900 mL

L = label claim of loratadine (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of loratadine (C₂₂H₂₃ClN₂O₂ ) 2S (USP41) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities, Procedure 1

Use Organic Impurities, Procedure 1 if Assay, Procedure 1 is used.

Buffer, Mobile phase, and Diluent: Prepare as directed in Assay, Procedure 1.

Sensitivity solution: 0.05 μg/mL of USP Loratadine RS in Mobile phase

Standard solution: 0.5 μg/mL of USP Loratadine RS in Mobile phase

Sample solution: Transfer 10 Tablets to a 500-mL volumetric flask, add 400 mL of acetonitrile, and stir for about 10 min. Sonicate the solution for 10 min, and stir for another 10 min. Dilute with acetonitrile to volume, and mix. Dilute an aliquot of the resulting solution with Diluent to obtain a solution that has a concentration of about 0.1 mg/mL, based on the label claim. Centrifuge the solution for about 10 min, and use the supernatant.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

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

Flow rate: 1.0 mL/min

Injection volume: 50 μL

System suitability

Samples: Sensitivity solution and Standard solution

Suitability requirements

Column e

ciency: NLT 3000 theoretical plates, Standard solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Tablets taken:

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

r_U = peak response of each impurity 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)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

Organic Impurities, Procedure 2

Use Organic Impurities, Procedure 2 if Assay, Procedure 2 is used.

Buffer, Mobile phase, Diluent, System suitability solution, and Sample solution: Prepare as directed in Assay, Procedure 2.

Sensitivity solution: 0.04 μg/mL of USP Loratadine RS in Diluent

Standard solution: 0.8 μg/mL of USP Loratadine RS in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 15-cm; 5-μm packing L7

Flow rate: 1.0 mL/min

Injection volume: 50 μL

System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

[Note—The relative retention times for loratadine related compound A, loratadine related compound C, loratadine related compound B, and loratadine are about 0.26, 0.31, 0.42, and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.2 between loratadine related compound A and loratadine related compound C; NLT 1.2 between loratadine related compound C and loratadine related compound B, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 4.0%, Standard solution

Signal-to-noise ratio: NLT 3.0, Sensitivity solution

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of each impurity in the portion of Tablets taken:

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

r_U = peak response of each impurity 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)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a These impurities are controlled in the drug substance and are listed here for information only. These impurities are not included when determining total impurities.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store between 20° and 25°.

Labeling: The labeling states with which Organic Impurities and Assay procedure the article complies, if other than Procedure 1. When more than one Disintegration test is given, the labeling states the Disintegration test used only if Test 1 is not used.

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.

C₁₉H₁₉ClN₂ 310.82

USP Loratadine Related Compound B RS

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

C₂₀H₂₁ClN₂ 324.85

USP Loratadine Related Compound C RS

8-Chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one.

C₁₄H₁₀ClNO 243.69