Galantamine 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

Galantamine Tablets contain an amount of Galantamine Hydrobromide equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of galantamine (C₁₇H₂₁NO₃).

2 IDENTIFICATION

Change to read:

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay (USP 1-May-2021)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

3.1 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 (USP 1-May-2021) and Buffer solution (1:19)

Solution B: Acetonitrile and methanol (USP 1-May-2021) (19:1)

Mobile phase: See Table 1.

Table 1

Diluent: Dissolve 35.4 g of edetate disodium in 950 mL of water, and add 50 mL of methanol. (USP 1-May-2021) [NOTE-First dissolve in water, and then add methanol.]

System suitability solution: 0.6 mg/mL of USP Galantamine Hydrobromide Related Compounds Mixture RS in Diluent (USP 1-May-2021)

Standard solution: 0.62 mg/mL of USP Galantamine Hydrobromide RS (equivalent to 0.48 mg/mL of galantamine) (USP 1-May-2021) in Diluent

Sample solution: Nominally (USP 1-May-2021) 0.48 mg/mL of galantamine from powdered Tablets (NLT 10) in Diluent. Pass through a PTFE filter of 0.45-µm or finer pore size.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 230 nm. For Identification A, use a diode array detector in the range of 200-300 nm. (USP 1-May-2021)

Column: 4.6-mm x 10-cm; 3-µm packing L1

Column temperature: 35°

Flow rate: 1.5 mL/min

Injection volume: 20 µL

3.3 System suitability

Samples: System suitability solution and (USP 1-May-2021) Standard solution

[NOTE-See Table 2 for the relative retention times.) (USP 1-MAY-2021)

Suitability requirements

Resolution: NLT 1.5 between galantamine N-oxide and dihydrogalantamine, System suitability solution (USP 1-May-2021)

Relative standard deviation: NMT 1.0%, (USP 1-May-2021) Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of galantamine (C₁₇H₂₁NO₃) in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x (M_r1/M_r2) 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

M_r1 = molecular weight of galantamine, 287.35

M_r2 = molecular weight of galantamine hydrobromide , 368.27

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 DISSOLUTION (711)

4.1.1 Test 1

Medium: Water: 500 mL

Apparatus 2: 50 rpm

Time: 20 min

Analyze the sample under test using either the Instrumental procedure or Chromatographic procedure.

Instrumental procedure (USP 1-May-2021)

Standard solution: (L/400) mg/mL of USP Galantamine Hydrobromide RS in Medium, where L is the label claim in mg/Tablet (USP 1-May-2021)

Sample solution: Passa portion (USP 1-May-2021) of the solution through a suitable filter of 0.2-µm pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 288 nm

Cell: 5-cm for 4-mg and 8-mg Tablets; 1-cm for 12-mg Tablets

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of galantamine (C₁₇H₂₁NO₃) dissolved in the portion of Tablets taken:

Result = (A_U/A_S) x (C_S/L) x (M_r1/M_r2) x V x 100

A_U = absorbance of galantamine from the Sample solution

A_S = absorbance of galantamine from the Standard solution

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

L = label claim (mg/Tablet)

M_r1 = molecular weight of galantamine, 287.35

M_r2 = molecular weight of galantamine hydrobromide, 368.27

V = volume of Medium, 500 mL

Chromatographic procedure

Buffer: 3.45 g/L of monobasic sodium phosphate in water. To each liter, add 1 mL of triethylamine. Adjust with phosphoric acid to a pH of 4.5.

Mobile phase: Acetonitrile, methanol, and Buffer (10:10:80), filtered and deaerated

Standard solution: (L/400) mg/mL of USP Galantamine Hydrobromide RS in water, where L is the label claim in mg/Tablet

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

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 230 nm

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

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention time of galantamine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Analysis

Relative standard deviation: NMT 2.0%

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of galantamine (C₁₇H₂₁NO₃) dissolved in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/L) x (M_r1/M_r2) x V x 100

r_U = peak area of galantamine from the Sample solution

r_S = peak area of galantamine from the Standard solution

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

L = label claim (mg/Tablet)

M_r1 = molecular weight of galantamine, 287.35

M_r2 = molecular weight of galantamine hydrobromide, 368.27

V = volume of Medium, 500 mL (USP 1-May-2021)

Tolerances: NLT 80% (Q) of the labeled amount of galantamine (C₁₇H₂₁NO₃) is dissolved.

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

Medium: Water; 500 mL

Apparatus 2: 50 rpm

Time: 20 min

Standard solution: (L/400) mg/mL of USP Galantamine Hydrobromide RS in Medium, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution through a suitable filter of 0.2-µm pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 288 nm

Cell: 5-cm for 4-mg and 8-mg Tablets; 1-cm for 12-mg Tablets

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of galantamine (C₁₇H₂₁NO₃) dissolved in the portion of Tablets taken:

Result = (A_U/A_S) x (C_S/L) x (M_r1/M_r2) x V x 100

A_U = absorbance of galantamine from the Sample solution

A_S = absorbance of galantamine from the Standard solution

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

L = label claim (mg/Tablet)

M_r1 = molecular weight of galantamine, 287.35

M_r2 = molecular weight of galantamine hydrobromide, 368.27

V = volume of Medium, 500 mL (USP 1-May-2021)

Tolerances: NLT 70% (Q) of the labeled amount of galantamine (C₁₇H₂₁NO₃) is dissolved.

4.1.3 Test 3: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 3

Medium: Water: 500 mL

Apparatus 2: 50 rpm. Use apex vessels and adjust the position of the paddle so that the distance between the tip of the peak and the bottom of the paddle is 1 cm.

Time: 20 min

Buffer: 3.45 g/L of monobasic sodium phosphate in water. To each liter, add 1 mL of triethylamine (USP 1-May-2021) Adjust with phosphoric acid to a pH of 4.5.

Mobile phase: Acetonitrile, methanol (USP 1-May-2021) and Buffer (10:10:80), filtered and deaerated

Standard solution: (L/400) mg/mL of USP Galantamine Hydrobromide RS in water, where L is the label claim in mg/Tablet (USP 1-May-2021)

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

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 230 nm

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

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 2 (USP 1-May-2021) times the retention time of galantamine

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 galantamine (C₁₇H₂₁NO₃) dissolved in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/L) x (M_r1/M_r2) x V x 100

r_U = peak area of galantamine from (USP 1-May-2021) the Sample solution

r_S = peak area of galantamine from (USP 1-May-2021) the Standard solution

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

L = label claim (mg/Tablet)

M_r1 = molecular weight of galantamine, 287.35

M_r2 = molecular weight of galantamine hydrobromide, 368.27

V = volume of Medium, 500 mL

Tolerances: NLT 80% (Q) of the labeled amount of galantamine (C₁₇H₂₁NO₃) is dissolved.

Change to read:

4.2 UNIFORMITY OF DOSAGE UNITS (905), Content Uniformity

Meet the requirements (USP 1-May-2021)

5 IMPURITIES

Change to read:

5.1 ORGANIC IMPURITIES

Buffer solution, Solution A, Solution B, Mobile phase, Diluent, System suitability solution, (USP 1-May-2021) Standard solution, and

Sample solution: Prepare as directed in the Assay.

Sensitivity solution: 0.6 µg/mL of USP Galantamine Hydrobromide RS (equivalent to 0.5 µg/mL of galantamine) from the Standard solution in Diluent (USP 1-May-2021)

5.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Injection volume: 20 µL

5.3 System suitability

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

[NOTE- See Table 2 for the relative retention times.) (USP 1-MAY-2021)

Suitability requirements

Resolution: NLT 1.5 between galantamine N-oxide and dihydrogalantamine, (USP 1-May-2021) System suitability solution

Relative standard deviation: NMT 2.0% for galantamine, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution (USP 1-May-2021)

5.4 Analysis

Samples: Standard solution and Sample solution

(USP 1-May-2021)

Calculate the percentage of any unspecified impurity (USP 1-May-2021) in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x (M_r1/M_r2) x (100/F)

r_U = peak area of each impurity from the Sample solution

r_S = peak area of galantamine from the Standard solution

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

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

M_r1 = molecular weight of galantamine, 287.35

M_r2 = molecular weight of galantamine hydrobromide, 368.27

F = relative response factor for each of the impurities relative to galantamine (see Table 2)

Acceptance criteria: See Table 2. Disregard the bromide peak near the void volume. The reporting threshold is 0.1%. (USP 1-May-2021)

Table 2

^a (4aS,6R,8aS)-3-Methoxy-4a,5,9,10,11,12-hexahydro-6H-benzo[2,3]benzofuro [4,3-cd]azepin-6-ol. (USP May 1, 2021)

^b (4aS,6R,8aS)-6-Hydroxy-3-methoxy-11-methyl-4a,5,9,10,11,12-hexahydro-6H-benzo[2,3]benzofuro[4,3-cd)azepine 11-oxide. (USP 1-May-2021)

^c (4aS,6R,8aS)-3-Methoxy-11-methyl-4a,5,7,8,9,10,11,12-octahydro-6H-benzo[2,3]benzofuro[4,3-cd]azepin-6-ol. (USP 1-May-2021)

^d This is a process impurity and is listed for information only. It is controlled in the drug substance.

^e (4aS,6S,8aS)-3-Methoxy-11-methyl-4a,5,9,10,11,12-hexahydro-6H-benzo[2,3]benzofuro[4,3-cd]azepin-6-ol. (USP 1-May-2021)

^f (4aS,8aS)-3-Methoxy-11-methyl-9,10,11,12-tetrahydro-4aH-benzo[2,3]benzofuro[4,3-cd]azepine. (USP 1-May-2021)

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed containers, and store at controlled room temperature.

Change to read:

6.2 LABELING

(USP 1-May-2021) The labeling states the Dissolution test used only if Test 1 is not used.

Change to read:

6.3 USP REFERENCE STANDARDS (11)

USP Galantamine Hydrobromide RS

USP Galantamine Hydrobromide Related Compounds Mixture RS

Contains a mixture of the following 5 compounds:

Galantamine hydrobromide.

Galantamine N-oxide;

(4aS,6R,8aS)-6-Hydroxy-3-methoxy-11-methyl-4a,5,9,10,11,12-hexahydro-6H-benzo[2,3]benzofuro[4,3-cd]azepine 11-oxide.

C₁₇H₂₁NO₄ 303.35

Dihydrogalantamine;

(4aS,6R,8aS)-3-Methoxy-11-methyl-4a,5,7,8,9,10,11,12-octahydro-6H-benzo[2,3]benzofuro[4,3-cd]azepin-6-ol.

C₁₇H₂₃NO₃ 289.37

6S-Galantamine;

(4aS,6S,8aS)-3-Methoxy-11-methyl-4a,5,9,10,11,12-hexahydro-6H-benzo[2,3]benzofuro[4,3-ca]azepin-6-ol.

C₁₇H₂₁NO₃ 287.35

Anhydrogalantamine;

(4aS,8aS)-3-Methoxy-11-methyl-9,10,11,12-tetrahydro-4aH-benzo[2,3]benzofuro[4,3-cd]azepine.

C₁₇H₁₉NO₂ 269.34

[NOTE-The contents have previously been referred to as galantamine hydrobromide, 6β-hexahydrogalantamine, 6β-octahydrogalantamine, 6α-hexahydrogalantamine, and tetrahydrogalantamine, respectively.] (USP 1-MAY-2021)