Action and use<\/strong><\/p>\n Cholinesterase inhibitor; treatment of Alzheimer\u2019s disease.<\/p>\n Preparations<\/strong><\/p>\n Galantamine Oral Solution<\/p>\n Galantamine Prolonged-release Capsules<\/p>\n Galantamine Tablets<\/p>\n (4aS,6R,8aS)-3-Methoxy-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-ol hydrobromide.<\/p>\n It is isolated from natural sources or produced by a synthetic process.<\/p>\n 99.0 per cent to 101.0 per cent (dried substance).<\/p>\n White or almost white, crystalline or amorphous powder.<\/p>\n Sparingly soluble in water, very slightly soluble in anhydrous ethanol. It dissolves in dilute solutions of alkali hydroxides.<\/p>\n A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n Comparison galantamine hydrobromide CRS.<\/p>\n B. Specific optical rotation or enantiomeric purity (see Tests).<\/p>\n C. It gives reaction (a) of bromides (2.3.1).<\/p>\n Dissolve 0.60 g in carbon dioxide-free water R and dilute to 30.0 mL with the same solvent.<\/p>\n 4.0 to 5.5 for solution S.<\/p>\n For galantamine from natural sources: -100 to -90 (dried substance), determined on solution S.<\/p>\n For galantamine produced by a synthetic process. Capillary electrophoresis (2.2.47). Prepare the solutions immediately before use.<\/p>\n Buffer electrolyte 8.9 g\/L solution of disodium hydrogen phosphate dihydrate R adjusted to pH 3.0 with phosphoric acid R.<\/p>\n Test solution: Dissolve 25.0 mg of the substance to be examined in 50.0 mL of water R and filter through a membrane filter (nominal pore size 0.22 \u03bcm).<\/p>\n Reference solution (a): Dissolve 5 mg of galantamine racemic mixture CRS in water R and dilute to 10 mL with the same solvent. Dilute 1 mL of the solution to 100 mL with water R and filter through a membrane filter (nominal pore size 0.22 \u03bcm).<\/p>\n Reference solution (b): Dilute 1.0 mL of the test solution to 100.0 mL with water R. Dilute 1.0 mL of this solution to 10.0 mL with water R and filter through a membrane filter (nominal pore size 0.22 \u03bcm).<\/p>\n Blank solution Filter water R through a membrane filter (nominal pore size 0.22 \u03bcm).<\/p>\n Capillary:<\/p>\n \u2014 material: uncoated fused silica;<\/p>\n \u2014 size: effective length = about 0.50 m, \u00d8 = 75 \u03bcm.<\/p>\n Temperature 20 \u00b0C.<\/p>\n CZE buffer: Dissolve 0.196 g of \u03b1-cyclodextrin R in 10.0 mL of buffer electrolyte and filter through a membrane filter (nominal pore size 0.22 \u03bcm).<\/p>\n Detection: Spectrophotometer at 214 nm.<\/p>\n Preconditioning of the capillary At 137.9 kPa, rinse the capillary for 5 min with water R and for 5 min with CZE buffer.<\/p>\n Injection Under pressure (3.45 kPa) for 4 s.<\/p>\n Migration Apply a voltage of 15 kV.<\/p>\n Run time 35 min.<\/p>\n Relative migration times: With reference to galantamine (migration time = about 18 min): impurity F = about 1.05.<\/p>\n System suitability Reference solution (a):<\/p>\n \u2014 resolution: minimum 2.5 between the peaks due to galantamine and impurity F.<\/p>\n Limit:<\/p>\n \u2014 impurity F: not more than 1.5 times the area of the principal peak in the electropherogram obtained with reference solution (b) (0.15 per cent).<\/p>\n Liquid chromatography (2.2.29).<\/p>\n A. Galantamine from natural sources<\/p>\n Solvent mixture: Mobile phase B, mobile phase A (10:90 V\/V).<\/p>\n Test solution: Dissolve 12 mg of the substance to be examined in the solvent mixture and dilute to 10.0 mL with the solvent mixture.<\/p>\n Reference solution (a): Dilute 1.0 mL of the test solution to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 10.0 mL with the solvent mixture.<\/p>\n Reference solution (b) Dissolve 5 mg of galantamine natural for system suitability CRS (containing impurities A and E) in the solvent mixture and dilute to 5 mL with the solvent mixture.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n \u2014 stationary phase: octylsilyl silica gel for chromatography R (5 \u03bcm);<\/p>\n \u2014 temperature: 30 \u00b0C.<\/p>\n Mobile phase:<\/p>\n \u2014 mobile phase A: dissolve 3.15 g of ammonium formate R in 900 mL of water for chromatography R, adjust to pH 3.8 with anhydrous formic acid R and dilute to 1000 mL with water for chromatography R;<\/p>\n \u2014 mobile phase B: acetonitrile R;<\/p>\n Flow rate 1.0 mL\/min.<\/p>\n Detection Spectrophotometer at 287 nm.<\/p>\n Injection 10 \u03bcL.<\/p>\n Identification of impurities Use the chromatogram supplied with galantamine natural for system suitability CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A and E.<\/p>\n Relative retention With reference to galantamine (retention time = about 12 min): impurity E = about 0.8; System suitability Reference solution (b):<\/p>\n \u2014 resolution: minimum 5.0 between the peaks due to impurity E and galantamine.<\/p>\n Limits:<\/p>\n \u2014 impurity E: not more than 6 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.6 per cent);<\/p>\n \u2014 impurity A: not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.15 per cent);<\/p>\n \u2014 unspecified impurities: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.10 per cent);<\/p>\n \u2014 total: not more than 8 times the area of the principal peak in the chromatogram obtained with reference \u2014 disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).<\/p>\n B. Galantamine produced by a synthetic process<\/p>\n Solvent mixture Dilute 50 mL of methanol R to 1000 mL with water R.<\/p>\n Test solution Dissolve 0.10 g of the substance to be examined in 50.0 mL of the solvent mixture and dilute to 100.0 mL with the solvent mixture.<\/p>\n Reference solution (a) Dilute 1.0 mL of the test solution to 100.0 mL with the solvent mixture. Dilute 5.0 mL of this solution to 10.0 mL with the solvent mixture.<\/p>\n Reference solution (b) Dissolve 2.5 mg of galantamine synthetic for system suitability CRS (containing impurities C and D) in the solvent mixture and dilute to 5 mL with the solvent mixture.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.10 m, \u00d8 = 4.6 mm;<\/p>\n \u2014 stationary phase: end-capped octadecylsilyl amorphous organosilica polymer for chromatography R (3.5 \u03bcm);<\/p>\n \u2014 temperature: 55 \u00b0C.<\/p>\n Mobile phase:<\/p>\n \u2014 mobile phase A: dissolve 0.79 g of disodium hydrogen phosphate dihydrate R and 2.46 g of sodium dihydrogen phosphate R in water for chromatography R and dilute to 1000 mL with the same solvent; to 950 mL of the solution add 50 mL of methanol R1;<\/p>\n \u2014 mobile phase B: acetonitrile for chromatography R;<\/p>\n Flow rate 1.5 mL\/min.<\/p>\n Detection: Spectrophotometer at 230 nm.<\/p>\n Injection 20 \u03bcL.<\/p>\n Identification of impurities: Use the chromatogram supplied with galantamine synthetic for system suitability CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities C and D.<\/p>\n Relative retention: With reference to galantamine (retention time = about 16 min): impurity C = about 0.8; System suitability Reference solution (b):<\/p>\n \u2014 resolution: minimum 4.5 between the peaks due to impurity C and galantamine.<\/p>\n Limits:<\/p>\n \u2014 impurities C, D: for each impurity, not more than 0.8 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.4 per cent);<\/p>\n \u2014 unspecified impurities: for each impurity, not more than 0.2 times the area of the principal peak in the \u2014 total: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a) (1.0 per cent);<\/p>\n \u2014 disregard limit: 0.1 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).<\/p>\n Maximum 1.0 per cent, determined on 1.000 g in an oven at 105 \u00b0C for 4 h.<\/p>\n Maximum 0.1 per cent, determined on 2.0 g.<\/p>\n Dissolve 0.275 g in 40 mL of water R. Add 40 mL of ethanol (96 per cent) R. Add 5 mL of 0.01 M hydrochloric acid. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20). Read the volume added between the 2 points of inflexion.<\/p>\n 1 mL of 0.1 M sodium hydroxide is equivalent to 36.83 mg of C17<\/sub>H22<\/sub>BrNO3<\/sub>.<\/p>\n The label states the origin of the substance:<\/p>\n \u2014 isolated from natural sources;<\/p>\n \u2014 produced by a synthetic process.<\/p>\n Test A for related substances A, B, E.<\/p>\n Specified impurities A, E. Other detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other\/unspecified impurities and\/or by the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10. Control of impurities in substances for pharmaceutical use) B.<\/p>\n Test B for related substances A, B, C, D, E, F.<\/p>\n Specified impurities C, D, F.<\/p>\n Other detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other\/unspecified impurities and\/or by the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10. Control of impurities in substances for pharmaceutical use) A, B, E.<\/p>\n A. (4aS,8aS)-3-methoxy-11-methyl-4a,5,9,10,11,12-hexahydro-6H-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-one (narwedine),<\/p>\n B. (4aS,6S,8aS)-3-methoxy-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-ol (epi-galantamine),<\/p>\n C. (4aS,6S,8aR)-3-methoxy-11-methyl-5,6,7,8,9,10,11,12-octahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-ol (dihydrogalantamine),<\/p>\n D. (4aS,8aS)-3-methoxy-11-methyl-9,10,11,12-tetrahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepine E. (4aS,6R,8aS)-3-methoxy-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-ol (N- F. (4aR,6S,8aR)-3-methoxy-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-ol (ent-galantamine).<\/p>\n","protected":false},"excerpt":{"rendered":" (Ph. Eur. monograph 2366) C17H22BrNO3\u00a0\u00a0 368.3\u00a0 \u00a01953-04-4 Action and use Cholinesterase inhibitor; treatment of Alzheimer\u2019s disease. Preparations Galantamine Oral Solution Galantamine Prolonged-release Capsules Galantamine Tablets DEFINITION (4aS,6R,8aS)-3-Methoxy-11-methyl-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-ol hydrobromide. It is isolated from natural sources or produced by a synthetic process. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost…<\/p>\n","protected":false},"author":3,"featured_media":12633,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-12606","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicinal-substances"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12606","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=12606"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12606\/revisions"}],"predecessor-version":[{"id":12636,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12606\/revisions\/12636"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/12633"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=12606"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=12606"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=12606"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}DEFINITION<\/h2>\n
Content<\/h3>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
Solubility<\/h3>\n
IDENTIFICATION<\/h2>\n
TESTS<\/h2>\n
Solution S<\/h3>\n
pH (2.2.3)<\/h3>\n
Specific optical rotation (2.2.7)<\/h3>\n
Enantiomeric purity<\/h3>\n
Related substances<\/h2>\n
\n\n
\n Time
\n(min)<\/td>\nMobile phase A
\n(per cent V\/V)<\/td>\nMobile phase B
\n(per cent V\/V)<\/td>\n<\/tr>\n\n 0 – 5<\/td>\n 95<\/td>\n 5<\/td>\n<\/tr>\n \n 5 – 20<\/td>\n 95 \u2192 80<\/td>\n 5 \u2192 20<\/td>\n<\/tr>\n \n 20 – 23<\/td>\n 80 \u2192 50<\/td>\n 20 \u2192 50<\/td>\n<\/tr>\n \n 23 – 31<\/td>\n 50 \u2192 20<\/td>\n 50 \u2192 80<\/td>\n<\/tr>\n \n 31 – 35<\/td>\n 20<\/td>\n 80<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
\nimpurity A = about 1.5.<\/p>\n
\nsolution (a) (0.8 per cent);<\/p>\n\n\n
\n Time
\n(min)<\/td>\nMobile phase A
\n(per cent V\/V)<\/td>\nMobile phase B
\n(per cent V\/V)<\/td>\n<\/tr>\n\n 0 – 6<\/td>\n 100<\/td>\n 0<\/td>\n<\/tr>\n \n 6 – 20<\/td>\n 100 \u2192 95<\/td>\n 0 \u2192 5<\/td>\n<\/tr>\n \n 20 – 35<\/td>\n 95 \u2192 85<\/td>\n 5 \u2192 15<\/td>\n<\/tr>\n \n 35 – 50<\/td>\n 85 \u2192 80<\/td>\n 15 \u2192 20<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
\nimpurity D = about 2.1.<\/p>\n
\nchromatogram obtained with reference solution (a) (0.10 per cent);<\/p>\nLoss on drying (2.2.32)<\/h4>\n
Sulfated ash (2.4.14)<\/h4>\n
ASSAY<\/h2>\n
LABELLING<\/h2>\n
IMPURITIES<\/h2>\n
![\"Galantamine](\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/1-132-300x163.jpg\")
<\/p>\n![\"Galantamine](\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/2-131-300x163.jpg\")
<\/p>\n![\"Galantamine](\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/3-122-300x163.jpg\")
<\/p>\n![\"Galantamine](\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/4-111-300x163.jpg\")
<\/p>\n
\n(anhydrogalantamine),<\/p>\n![\"Galantamine](\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/5-87-300x163.jpg\")
<\/p>\n
\ndemethylgalantamine),<\/p>\n![\"Galantamine](\"https:\/\/nhathuocngocanh.com\/bp\/wp-content\/uploads\/2025\/10\/6-74-300x163.jpg\")
<\/p>\n