Galantamine Tablets
DEFINITION
Galantamine Tablets contain an amount of Galantamine Hydrobromide equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of galantamine (C17H21NO3).
IDENTIFICATION
• A. Ultraviolet Absorption 
197U
:
The spectrum of the Sample solution corresponds to that of the Standard solution, as obtained in the test for Uniformity of Dosage Units.
197U:
The spectrum of the Sample solution corresponds to that of the Standard solution, as obtained in the test for Uniformity of Dosage Units.
• 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
Buffer solution:
5.34 g/L of dibasic sodium phosphate dihydrate in water. Adjust with phosphoric acid to a pH of 6.5.
Solution A:
Methanol and Buffer solution (1:19)
Solution B:
Acetonitrile and methanol (19:1)
Mobile phase:
See the gradient table below.
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 100 | 0 |
| 40.0 | 75 | 25 |
| 45.0 | 60 | 40 |
| 46.0 | 40 | 60 |
| 55.0 | 40 | 60 |
| 56.0 | 100 | 0 |
| 61.0 | 100 | 0 |
Diluent:
Dissolve 35.4 g of edetate disodium in 950 mL water, and add 50 mL of methanol. [Note—First dissolve in water, then add methanol. ]
Standard solution:
0.62 mg/mL of USP Galantamine Hydrobromide RS, in Diluent
Sample solution:
0.48 mg/mL of galantamine from powdered Tablets (NLT 10) in Diluent. Pass through a PTFE filter having a 0.45-µm or finer pore size.
Chromatographic system
Mode:
LC
Detector:
UV 230 nm
Column:
4.6-mm × 10-cm; 3-µm L1 packing
Column temperature:
35
Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the quantity, as a percentage of the label claim, of C17H21NO3 in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Galantamine Hydrobromide RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of galantamine in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of galantamine, 287.35 |
| Mr2 | = | = molecular weight of galantamine hydrobromide, 368.27 |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
711
Test 1
Medium:
Water; 500 mL
Apparatus 2:
50 rpm
Time:
20 min
Standard solution:
(L/500) mg/mL in Medium, where L is the label claim in mg
Sample solution:
Pass portions of the solution through a suitable filter of 0.2-µm pore size.
Spectrometric conditions
Mode:
UV
Analytical wavelength:
288 nm
Cell:
5-cm cell for 4-mg and 8-mg Tablets; 1-cm cell for 12-mg Tablets
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C17H21NO3 dissolved in the portion of Tablets taken:
Result = (AU/AS) × (CS/L) × (Mr1/Mr2) × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of USP Galantamine Hydrobromide RS in the Standard solution (mg/mL) |
| L | = | = Tablet label claim (mg) |
| Mr1 | = | = molecular weight of galantamine, 287.35 |
| Mr2 | = | = molecular weight of galantamine hydrobromide, 368.27 |
Tolerances:
NLT 80% (Q) of the labeled amount of galantamine is dissolved.
Test 2:
If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.
Medium, Apparatus 2, Time, Standard solution, Sample solution, and Analysis:
Proceed as directed for Test 1.
Tolerances:
NLT 70% (Q) of the labeled amount of galantamine is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements for coated Tablets
905:
Meet the requirements for coated Tablets
Procedure for content uniformity
Standard solution:
0.05 mg/mL of USP Galantamine Hydrobromide RS, in 0.1 N hydrochloric acid
Sample solution:
Add 1 Tablet to each appropriately sized volumetric flask to obtain a final galantamine concentration of 0.04 mg/mL, add an appropriate amount of 0.1 N hydrochloric acid, equivalent to 75% of the total volume of the volumetric flask, and mechanically shake for 45 min. Dilute with 0.1 N hydrochloric acid to volume. Pass a portion of this solution through a suitable filter of 0.2-µm pore size, and use the filtrate.
Spectrometric conditions
Mode:
UV
Analytical wavelength:
Absorption maximum at about 289 nm
Analysis
Samples:
Standard solution and Sample solution
Determine the amount of C17H21NO3 dissolved in filtered portions of the Sample solution in comparison with the Standard solution.
Calculate the quantity, as a percentage of the label claim, of C17H21NO3 dissolved:
Result = (AU/AS) × (CS/CU) × (Mr1/Mr2) × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of USP Galantamine Hydrobromide RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of galantamine, 287.35 |
| Mr2 | = | = molecular weight of galantamine hydrobromide, 368.27 |
IMPURITIES
Organic Impurities
• Procedure
Buffer solution, Solution A, Solution B, Mobile phase, Diluent, Standard solution, and Sample solution:
Proceed as directed in the Assay.
System suitability solution:
0.6 mg/mL of USP Galantamine Hydrobromide Related Compounds Mixture RS in Diluent
System suitability
Samples:
Standard solution and System suitability solution
Suitability requirements
Resolution:
NLT 1.5 between 6
-hexahydrogalantamine and 6-octahydrogalantamine, System suitability solution
-hexahydrogalantamine and 6-octahydrogalantamine, System suitability solution
Relative standard deviation:
NMT 2.0% for galantamine, Standard solution
[Note—Identify the impurities using the approximate relative retention times given in Impurity Table 1. ]
Analysis
Samples:
Standard solution and Sample solution
[Note—Ignore the peak due to bromide near the void volume. ]
Calculate the percentage of each of the impurities including the unspecified degradation impurities in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × (100/F)
| rU | = | = peak area of each impurity from the Sample solution |
| rS | = | = peak area of galantamine from the Standard solution |
| CS | = | = concentration of USP Galantamine Hydrobromide RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of galantamine in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of galantamine, 287.35 |
| Mr2 | = | = molecular weight of galantamine hydrobromide, 368.27 |
| F | = | = relative response factor for each of the impurities relative to galantamine (see Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 1.5%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| N-Desmethylgalantaminea | 0.41 | 1.1 | 0.5 |
| 6-Hexahydrogalantamine (also known as galantamine N- oxide)b |
0.73 | 1.1 | 0.75 |
| 6-Octahydrogalantamine (also known as lycoramine)c* |
0.86 | — | — |
| Galantamine hydrobromide | 1.00 | 1.0 | — |
6 -Hexahydrogalantamine (also known as epigalantamine)d |
1.15 | 1.1 | 0.5 |
| Tetrahydrogalantaminee* | 2.09 | — | — |
| Individual, unspecified degradation impurity | — | 1.0 | 0.2 |
|
*
Impurities are not quantified and are intended for system suitability evaluation only.
a
(4aS,6R,8aS)-4a,5,9,10,11,12-Hexahydro-3-methoxy-6H-benzofuro[3a,3,2-ef][2]benzazepin-6-ol.
b
[4aS-(4
,6,8aR*)]-4a,5,9,10,11,12-Hexahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef][2]benzazepin-6-ol, N-oxide.
c
[4aS-(4a
,6,8aR*)]-4a,5,7,8,9,10,11,12-Octahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef][2]benzazepin-6-ol.
d
[4aS-(4a
,6,8aR*)]-4a,5,9,10,11,12-Hexahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef][2]benzazepin-6-ol.
e
[4aS-(4aR*,8aR*)]-9,10,11,12-Tetrahydro-3-methoxy-11-methyl-4aH-benzofuro[3a,3,2-ef][2]benzazepine.
|
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ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers, and store at controlled room temperature.
• Labeling:
When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
• USP Reference Standards 11
11
USP Galantamine Hydrobromide RS 
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USP Galantamine Hydrobromide Related Compounds Mixture RS
Contains galantamine hydrobromide, 6-hexahydrogalantamine, 6-octahydrogalantamine, 6-hexahydrogalantamine, and tetrahydrogalantamine.
Contains galantamine hydrobromide, 6
-hexahydrogalantamine, 6-octahydrogalantamine, 6-hexahydrogalantamine, and tetrahydrogalantamine.
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 |
| 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 3314
Pharmacopeial Forum: Volume No. 35(5) Page 1145