{"id":2693,"date":"2025-09-22T15:13:47","date_gmt":"2025-09-22T08:13:47","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=2693"},"modified":"2025-10-02T13:43:24","modified_gmt":"2025-10-02T06:43:24","slug":"benzydamine-hydrochloride","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/benzydamine-hydrochloride\/","title":{"rendered":"Benzydamine Hydrochloride"},"content":{"rendered":"

(Ph. Eur. monograph 2759)<\/p>\n

C_{19<\/sub>H_{24<\/sub>ClN_{3<\/sub>O\u00a0 \u00a0345.9\u00a0 \u00a0132-69-4<\/p>\n}}}

Action and use<\/strong><\/p>\n

Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory.<\/p>\n

Preparations<\/strong><\/p>\n

Benzydamine Cream<\/p>\n

Benzydamine Mouthwash<\/p>\n

Benzydamine Oromucosal Spray<\/p>\n

DEFINITION<\/h2>\n
3-[(1-Benzyl-1H-indazol-3-yl)oxy]-N,N-dimethylpropan-1-amine hydrochloride.<\/p>\n
Content<\/h3>\n
99.0 per cent to 101.0 per cent (dried substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or almost white, hygroscopic, crystalline powder.<\/p>\n
Solubility<\/h3>\n
Very soluble in water, freely soluble in ethanol (96 per cent) and in methylene chloride, slightly soluble in acetone, practically insoluble in heptane.<\/p>\n
IDENTIFICATION<\/h2>\n
A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison benzydamine hydrochloride CRS.<\/p>\n
B. It gives reaction (a) of chlorides (2.3.1).<\/p>\n
TESTS<\/h2>\n
Impurity G<\/h3>\n
Liquid chromatography (2.2.29) coupled with mass spectrometry (2.2.43).<\/p>\n
Solvent mixture: Mobile phase A, mobile phase B (8:92 V\/V).<\/p>\n
Test solution: Dissolve 25.0 mg of the substance to be examined in the solvent mixture and dilute to 25.0 mL with the solvent mixture.<\/p>\n
Reference solution: Dissolve 5.0 mg of benzydamine impurity G CRS in methanol R and dilute to 1000.0 mL with methanol R. Dilute 1.0 mL of this solution to 1000.0 mL with the solvent mixture.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.10 m, \u00d8 = 3.0 mm;<\/p>\n
\u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography compatible with 100 per cent aqueous mobile phases R (2.5 \u03bcm);<\/p>\n
\u2014 temperature: 40 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: in 1000 mL of methanol R3 mix 500 \u03bcL of formic acid R and 130 \u03bcL of heptafluorobutyric acid R;<\/p>\n
\u2014 mobile phase B: in 1000 mL of water for chromatography R mix 500 \u03bcL of formic acid R and 130 \u03bcL of heptafluorobutyric acid R;<\/p>\n\n\n\n\n\n\n\n
Time
\n(min)<\/td>\n Mobile phase A
\n(per cent V\/V)<\/td>\n Mobile phase B
\n(per cent V\/V)<\/td>\n<\/tr>\n
0 – 9<\/td>\n 8<\/td>\n 92<\/td>\n<\/tr>\n
9 – 15<\/td>\n 8 \u2192 26<\/td>\n 92 \u2192 74<\/td>\n<\/tr>\n
15 – 15.1<\/td>\n \u00a026 \u2192 80<\/td>\n 74 \u2192 20<\/td>\n<\/tr>\n
15.1 – 20<\/td>\n 80<\/td>\n 20<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate 0.3 mL\/min.<\/p>\n
Detection Mass detector: the following settings have been found to be suitable for triple-quadrupole mass spectrometer and are given as examples; if the detector has different setting parameters, adjust the detector settings so as to comply with the system suitability criteria:<\/p>\n
\u2014 ionisation: ESI-positive;<\/p>\n
\u2014 ion spray voltage: 5.5 kV;<\/p>\n
\u2014 ion source temperature: 350 \u00b0C;<\/p>\n
\u2014 declustering potential: 67 V;<\/p>\n
\u2014 Q1\/Q3 resolution: unit resolution;<\/p>\n
\u2014 dwell time: 500 ms;<\/p>\n
\u2014 acquisition starting time: 4 min;<\/p>\n
\u2014 acquisition ending time: 16 min;<\/p>\n
\u2014 ion transition: 122.1 m\/z to 46.0 m\/z;<\/p>\n
\u2014 collision energy: 30 eV.<\/p>\n
Injection 6 \u03bcL.<\/p>\n
Retention time: Impurity G = about 7 min.<\/p>\n
System suitability: Reference solution:<\/p>\n
\u2014 repeatability: maximum relative standard deviation of 5.0 per cent for the area of the peak due to impurity G determined on 6 injections using the extracted ion chromatogram showing the total ion current of the ion transition used for quantification.<\/p>\n
Calculation of content:<\/p>\n
\u2014 use the concentration of impurity G in the reference solution.<\/p>\n
Limit:<\/p>\n
\u2014 impurity G: maximum 5 ppm.<\/p>\n
Related substances<\/p>\n
Liquid chromatography (2.2.29).<\/p>\n
Solvent mixture methanol R, water R (50:50 V\/V).<\/p>\n
Test solution: Dissolve 25.0 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 benzydamine for system suitability CRS (containing impurities A, B and D) in 5 mL of the solvent mixture.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase: amidoalkylsilyl silica gel for chromatography R (5 \u03bcm).<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: dissolve 1.36 g of potassium dihydrogen phosphate R in 900 mL of water for chromatography R, adjust to pH 3.0 with phosphoric acid R, add 1.16 g of sodium octanesulfonate R and dilute to 1000 mL with water for chromatography R;<\/p>\n
\u2014 mobile phase B: methanol R;<\/p>\n\n\n\n\n\n\n
Time
\n(min)<\/td>\n Mobile phase A
\n(per cent V\/V)<\/td>\n Mobile phase B
\n(per cent V\/V)<\/td>\n<\/tr>\n
0 – 2<\/td>\n 50<\/td>\n 50<\/td>\n<\/tr>\n
2 – 22<\/td>\n 50 \u2192 35<\/td>\n 50 \u2192 65<\/td>\n<\/tr>\n
22 – 29<\/td>\n 35<\/td>\n 65<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate 1.5 mL\/min.<\/p>\n
Detection: Spectrophotometer at 320 nm.<\/p>\n
Equilibration: At least 10 min with the mobile phase at the initial composition.<\/p>\n
Injection 20 \u03bcL.<\/p>\n
Identification of impurities: Use the chromatogram supplied with benzydamine for system suitability CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A, B and D.<\/p>\n
Relative retention: With reference to benzydamine (retention time = about 12 min): impurity A = about 1.36; impurity D = about 1.43; impurity B = about 2.0.<\/p>\n
System suitability:<\/p>\n
\u2014 resolution: minimum 1.5 between the peaks due to impurities A and D in the chromatogram obtained with reference solution (b);<\/p>\n
\u2014 signal-to-noise ratio: minimum 38 for the principal peak in the chromatogram obtained with reference solution (a). Calculation of percentage contents:<\/p>\n
\u2014 correction factors: multiply the peak areas of the following impurities by the corresponding correction factor: impurity A = 1.9; impurity D = 1.4;<\/p>\n
\u2014 for each impurity, use the concentration of benzydamine hydrochloride in reference solution (a).<\/p>\n
Limits:<\/p>\n
\u2014 impurity B: maximum 0.5 per cent;<\/p>\n
\u2014 impurity A: maximum 0.2 per cent;<\/p>\n
\u2014 impurity D: maximum 0.15 per cent;<\/p>\n
\u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n
\u2014 total: maximum 1.0 per cent;<\/p>\n
\u2014 reporting threshold: 0.05 per cent.<\/p>\n
Loss on drying (2.2.32)<\/h4>\n
Maximum 1.0 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C for 3 h.<\/p>\n
Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n
ASSAY<\/h2>\n
Dissolve 0.300 g in 50 mL of ethanol (96 per cent) R. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20).<\/p>\n
1 mL of 0.1 M sodium hydroxide is equivalent to 34.59 mg of C_{19<\/sub>H_{24<\/sub>ClN_{3<\/sub>O.<\/p>\n}}}
STORAGE<\/h2>\n
In an airtight container.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities A, B, D, G.<\/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) C, E, F.<\/p>\n
$\"Benzydamine$ <\/p>\n
A. 3-(dimethylamino)propyl 2-(benzylamino)benzoate,<\/p>\n
$\"Benzydamine$ <\/p>\n
B. 3-[(1,5-dibenzyl-1H-indazol-3-yl)oxy]-N,N-dimethylpropan-1-amine,<\/p>\n
$\"Benzydamine$ <\/p>\n
C. 1-benzyl-1,2-dihydro-3H-indazol-3-one,<\/p>\n
$\"Benzydamine$ <\/p>\n
D. N -[3-[(1-benzyl-1H-indazol-3-yl)oxy]propyl]-N ,N ,N -trimethylpropane-1,3-diamine,<\/p>\n
$\"Benzydamine$ <\/p>\n
E. 1-benzyl-2-[3-(dimethylamino)propyl]-1,2-dihydro-3H-indazol-3-one,<\/p>\n
$\"Benzydamine$ <\/p>\n
F. 3-(dimethylamino)propyl 2-aminobenzoate,<\/p>\n
$\"Benzydamine$ <\/p>\n
G. 3-chloro-N,N-dimethylpropan-1-amine.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 2759) C19H24ClN3O\u00a0 \u00a0345.9\u00a0 \u00a0132-69-4 Action and use Cyclo-oxygenase inhibitor; analgesic; anti-inflammatory. Preparations Benzydamine Cream Benzydamine Mouthwash Benzydamine Oromucosal Spray DEFINITION 3-[(1-Benzyl-1H-indazol-3-yl)oxy]-N,N-dimethylpropan-1-amine hydrochloride. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white, hygroscopic, crystalline powder. Solubility Very soluble in water, freely soluble in ethanol (96 per…<\/p>\n","protected":false},"author":3,"featured_media":2777,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-2693","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\/2693","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=2693"}],"version-history":[{"count":5,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/2693\/revisions"}],"predecessor-version":[{"id":7794,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/2693\/revisions\/7794"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/2777"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=2693"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=2693"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=2693"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Content<\/h3>\n99.0 per cent to 101.0 per cent (dried substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\nWhite or almost white, hygroscopic, crystalline powder.<\/p>\n

Solubility<\/h3>\nVery soluble in water, freely soluble in ethanol (96 per cent) and in methylene chloride, slightly soluble in acetone, practically insoluble in heptane.<\/p>\n

IDENTIFICATION<\/h2>\nA. Infrared absorption spectrophotometry (2.2.24).<\/p>\nComparison benzydamine hydrochloride CRS.<\/p>\nB. It gives reaction (a) of chlorides (2.3.1).<\/p>\n

TESTS<\/h2>\n

Loss on drying (2.2.32)<\/h4>\nMaximum 1.0 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C for 3 h.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\nMaximum 0.1 per cent, determined on 1.0 g.<\/p>\n

ASSAY<\/h2>\nDissolve 0.300 g in 50 mL of ethanol (96 per cent) R. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20).<\/p>\n1 mL of 0.1 M sodium hydroxide is equivalent to 34.59 mg of C19<\/sub>H24<\/sub>ClN3<\/sub>O.<\/p>\n

STORAGE<\/h2>\nIn an airtight container.<\/p>\n

Content<\/h3>\n
99.0 per cent to 101.0 per cent (dried substance).<\/p>\n

Appearance<\/h3>\n
White or almost white, hygroscopic, crystalline powder.<\/p>\n

Solubility<\/h3>\n
Very soluble in water, freely soluble in ethanol (96 per cent) and in methylene chloride, slightly soluble in acetone, practically insoluble in heptane.<\/p>\n

IDENTIFICATION<\/h2>\n
A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison benzydamine hydrochloride CRS.<\/p>\n
B. It gives reaction (a) of chlorides (2.3.1).<\/p>\n

Loss on drying (2.2.32)<\/h4>\n
Maximum 1.0 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C for 3 h.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n

ASSAY<\/h2>\n
Dissolve 0.300 g in 50 mL of ethanol (96 per cent) R. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20).<\/p>\n
1 mL of 0.1 M sodium hydroxide is equivalent to 34.59 mg of C_{19<\/sub>H_{24<\/sub>ClN_{3<\/sub>O.<\/p>\n}}}

STORAGE<\/h2>\n
In an airtight container.<\/p>\n