Donepezil Hydrochloride Orally Disintegrating Tablets
DEFINITION
Donepezil Hydrochloride Orally Disintegrating Tablets contains NLT 93.0% and NMT 107.0% of the labeled amount of donepezil hydrochloride (C24H29NO3·HCl).
IDENTIFICATION
• A. Ultraviolet Absorption 
197U
197U
Sample solution:
Crush a suitable number of Tablets, and transfer an amount of powder, equivalent to 10 mg of donepezil hydrochloride, to a 100-mL volumetric flask. Add 80 mL of 0.1 N hydrochloric acid, and sonicate for 5 min. Cool to room temperature, and dilute with 0.1 N hydrochloric acid to volume. Transfer a portion to a centrifuge tube, and centrifuge for 15 min. Transfer 5 mL of the clear supernatant to a 25-mL volumetric flask, and dilute with 0.1 N hydrochloric acid to volume.
Analysis
Wavelength range:
220–360 nm
Acceptance criteria:
230, 271, and 315 nm
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Diluent:
Methanol and 0.1 N hydrochloric acid (3:1)
Mobile phase:
Dissolve 2.5 g of sodium decanesulfonate in 650 mL of water, and add 1.0 mL of perchloric acid and 350 mL of acetonitrile. If necessary, adjust with an additional 0.5 mL of perchloric acid to a pH of about 1.8.
System suitability solution:
0.4 mg/mL of USP Donepezil Hydrochloride RS and 0.016 mg/mL of USP Donepezil Related Compound A RS, prepared by dissolving in 40% of the flask volume of methanol and diluting with water to volume.
Standard solution:
0.4 mg/mL of USP Donepezil Hydrochloride RS in Diluent
Sample solution:
0.4 mg/mL of donepezil hydrochloride in Diluent, prepared by transferring a suitable number of Tablets to an appropriate volumetric flask containing 10 mL of 0.1 N hydrochloric acid. Shake to disintegrate the Tablets. Add 60% of the flask volume of Diluent, sonicate for 10 min, allow to cool to room temperature, and dilute with Diluent to volume.
Chromatographic system
Mode:
LC
Detector:
UV 271 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Column temperature:
35
Flow rate:
1.4 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
[Note—The relative retention times of donepezil related compound A and donepezil are about 0.92 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 1.5 between donepezil related compound A and donepezil, System suitability solution
Tailing factor:
NMT 1.5 for donepezil, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C24H29NO3·HCl in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of donepezil hydrochloride from the Sample solution |
| rS | = | = peak response of donepezil hydrochloride from the Standard solution |
| CS | = | = concentration of USP Donepezil Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of donepezil hydrochloride in the Sample solution (mg/mL) |
Acceptance criteria:
93.0%–107.0%
PERFORMANCE TESTS
• Disintegration 701
701
Time:
NMT 60 s
• Dissolution 711
711
Medium:
0.1 N hydrochloric acid; 900 mL
Apparatus 2:
50 rpm
Time:
30 min
Diluent:
Methanol and 0.1 N hydrochloric acid (3:1)
Mobile phase:
Acetonitrile, perchloric acid, and water (350:1:650)
Standard stock solution:
1.1 mg/mL of USP Donepezil Hydrochloride RS in Diluent. Dilute with Medium to obtain a concentration of 0.11 mg/mL.
Standard solution:
Dilute the Standard stock solution with Medium to obtain a concentration of L/1000 mg/mL, where L is the Tablet label claim in mg.
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 271 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Column temperature:
35
Flow rate:
1 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 5000 theoretical plates
Tailing factor:
NMT 1.5
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C24H29NO3·HCl dissolved.
Result = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response 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 C24H29NO3·HCl is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Mobile phase, System suitability solution, Sample solution, and Chromatographic system:
Proceed as directed in the Assay.
Standard solution:
0.8 µg/mL of USP Donepezil Hydrochloride RS in Diluent
System suitability
Samples:
System suitability solution and Standard solution
[Note—The relative retention times of donepezil related compound A and donepezil are about 0.92 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 1.5 between donepezil related compound A and donepezil, System suitability solution
Relative standard deviation:
NMT 8.0%, Standard solution
Analysis
Samples:
Sample solution and Standard solution.
[Note—Identify the impurities, using the relative retention times given in Impurity Table 1. ]
Calculate the percentage of any individual impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of any individual impurity from the Sample solution |
| rS | = | = peak response of donepezil hydrochloride from the Standard solution |
| CS | = | = concentration of USP Donepezil Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of donepezil hydrochloride in the Sample solution (mg/mL) |
| F | = | = relative response factor of each related compound, as listed in Impurity Table 1 |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Desbenzyl donepezila | 0.35 | 1.0 | 0.5 |
| Donepezil open ringb | 0.70 | 0.6 | 0.5 |
| Donepezil hydrochloride | 1.0 | — | — |
| Donepezil N-oxidec | 1.2 | 1.0 | 0.5 |
| Individual unspecified degradation impurity | — | — | 0.2 |
| Total Impurities | — | — | 1.0 |
|
a
5,6-Dimethoxy-2-(piperidin-4-ylmethyl)indan-1-one.
b
2-(3-(1-Benzylpiperidin-4-yl)-2-oxopropyl)-4,5-dimethoxybenzoic acid.
c
2-[(1-Benzylpiperidin-4-yl)methyl]-5,6-dimethoxyindan-1-one N-oxide.
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers, and store at controlled room temperature.
• USP Reference Standards 11
11
USP Donepezil Hydrochloride RS 
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USP Donepezil Related Compound A RS
(E)-2-[(1-Benzylpiperidin-4-yl)methylene]-5,6-dimethoxyindan-1-one.
C24H27NO3 377.48
(E)-2-[(1-Benzylpiperidin-4-yl)methylene]-5,6-dimethoxyindan-1-one.
C24H27NO3 377.48
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Ravi Ravichandran, Ph.D.
Principal Scientific Liaison 1-301-816-8330 |
(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 2970
Pharmacopeial Forum: Volume No. 36(3) Page 660