Add the following:
Loratadine Orally Disintegrating Tablets
DEFINITION
Loratadine Orally Disintegrating Tablets contain NLT 95.0% and NMT 105.0% of the labeled amount of loratadine (C22H23ClN2O2).
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.
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 Procedure 2. ]
• 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 having a concentration of about 0.1 mg/mL, based on the label claim. Pass a portion of this solution through a PVDF filter of 0.45-µm pore size, and discard the first 5 mL of filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
1.0 mL/min
Injection size:
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 in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of loratadine from the Sample solution |
| rS | = | = peak response of loratadine from the Standard solution |
| CS | = | = concentration of USP Loratadine RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of loratadine in the Sample solution (mg/mL) |
Acceptance criteria:
95.0%–105.0%
• 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 dissolving. ]
Sample solution:
Transfer a number 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
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 15-cm; 5-µm packing L7
Flow rate:
1.0 mL/min
Injection size:
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 and 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 in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of loratadine from the Sample solution |
| rS | = | = peak response of loratadine from the Standard solution |
| CS | = | = concentration of USP Loratadine RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of loratadine in the Sample solution (mg/mL) |
Acceptance criteria:
95.0%–105.0%
PERFORMANCE TESTS
• Disintegration 
701
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
• Dissolution 711
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.
Analysis
Detector:
UV 278 nm
Cell length:
1 cm
Blank:
Medium
Calculate the percentage of the labeled amount of loratadine (C22H23ClN2O2) dissolved:
Result = (AU/AS) × CS × (V/L) × 100
| AU | = | = absorbance from the Sample solution |
| AS | = | = absorbance from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of loratadine is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure 1
[Note—Use Organic Impurities, Procedure 1 if Assay, Procedure 1 is used. ]
Buffer, Mobile phase, and Diluent:
Proceed as directed in Assay, Procedure 1.
System 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 into 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 having 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
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
1.0 mL/min
Injection size:
50 µL
System suitability
Samples:
System sensitivity solution and Standard solution
Suitability requirements
Signal-to-noise ratio:
NLT 10, System sensitivity solution
Column efficiency:
NLT 3000 theoretical plates, Standard 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 each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of loratadine from the Standard solution |
| CS | = | = concentration of USP Loratadine RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of loratadine in the Sample solution (mg/mL) |
| F | = | = relative response factor (see Table 1) |
Acceptance criteria:
See Table 1.
Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Loratadine related compound C | 0.5 | 0.64 | 0.2 |
| Loratadine | 1.0 | — | — |
| Individual unspecified impurity | — | 1.0 | 0.1 |
| Total impurities | — | — | 0.3 |
• Procedure 2
[Note—Use Organic Impurities, Procedure 2 if Assay, Procedure 2 is used. ]
Buffer, Mobile phase, Diluent, Sample solution, and System suitability solution:
Proceed as directed in Assay, Procedure 2.
System 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
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 15-cm; 5-µm packing L7
Flow rate:
1.0 mL/min
Injection size:
50 µL
System suitability
Samples:
System suitability solution, Standard solution, and System sensitivity 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 and 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, System sensitivity solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of loratadine from the Standard solution |
| CS | = | = concentration of USP Loratadine RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of loratadine in the Sample solution (mg/mL) |
| F | = | = relative response factor (see Table 2) |
Acceptance criteria:
See Table 2.
Table 2
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Loratadine related compound A | 0.26 | 0.9 | 0.1 |
| Loratadine related compound Ba | 0.42 | — | — |
| Unspecified impuritya |
0.76 | — | — |
| Loratadine | 1.0 | — | — |
| Unspecified impuritya |
1.5 | — | — |
| Individual unspecified impurity | — | 1.0 | 0.1 |
| Total impurities | — | — | 0.1 |
|
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.
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ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers. Store between 20
and 25.
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
11
USP Loratadine RS 
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USP Loratadine Related Compound A RS
8-Chloro-6,11-dihydro-11-(4-piperidylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine.
C19H19ClN2 310.83
8-Chloro-6,11-dihydro-11-(4-piperidylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine.
C19H19ClN2 310.83
USP Loratadine Related Compound B RS
8-Chloro-6,11-dihydro-11-(N-methyl-4-piperidylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine.
C20H21ClN2 324.88
8-Chloro-6,11-dihydro-11-(N-methyl-4-piperidylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine.
C20H21ClN2 324.88
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
8-Chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one.
C14H10ClNO 243.69
USP35
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Mary S. Waddell
Scientific Liaison 1-301-816-8124 |
(SM42010) Monographs - Small Molecules 4 |
| 701 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3714
Pharmacopeial Forum: Volume No. 36(6) Page 1550