{"id":20624,"date":"2025-10-27T15:48:03","date_gmt":"2025-10-27T08:48:03","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=20624"},"modified":"2025-11-15T17:13:08","modified_gmt":"2025-11-15T10:13:08","slug":"salbutamol-pressurised-inhalation-suspension","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/salbutamol-pressurised-inhalation-suspension\/","title":{"rendered":"Salbutamol Pressurised Inhalation, Suspension"},"content":{"rendered":"

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

Beta2<\/sub>-adrenoceptor agonist; bronchodilator.<\/p>\n

DEFINITION<\/h2>\n

Salbutamol Pressurised Inhalation, Suspension is a suspension of Salbutamol Sulfate in a suitable liquid in a pressurised container fitted with a metering dose valve.<\/p>\n

The pressurised inhalation, suspension complies with the requirements stated under Preparations for Inhalation and with the following requirements.<\/p>\n

PRODUCTION<\/h2>\n

The size of aerosol particles to be inhaled is controlled so that a consistent portion is deposited in the lungs. The fine-particle characteristics of preparations for inhalation are determined using the method described in Appendix XII C7.<\/p>\n

Preparations for inhalation: Aerodynamic Assessment of Fine Particles. The test and limits should be agreed with the competent authority.<\/p>\n

The water content is controlled to ensure the performance of the product as justified and authorised by the competent authority.<\/p>\n

Content of salbutamol, C13<\/sub>H21<\/sub>NO3<\/sub><\/strong><\/p>\n

85.0 to 115.0% of the stated delivered dose (ex-actuator).<\/p>\n

IDENTIFICATION<\/h2>\n

Discharge the inhaler a sufficient number of times into a mortar to obtain the equivalent of 2 mg of salbutamol, grind the residue thoroughly with 0.1 g of potassium bromide, add a further 0.2 g of potassium bromide and mix thoroughly. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of salbutamol sulfate (RS 315).<\/p>\n

TESTS<\/h2>\n

Related substances<\/h3>\n

Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in mobile phase A.<\/p>\n

(1) Shake a quantity of the pressurised inhalation containing the equivalent of 1 mg of salbutamol with 10 mL of mobile phase A, mix with the aid of ultrasound and filter.<\/p>\n

(2) Dilute 1 volume of solution (1) to 20 volumes and further dilute 1 volume to 10 volumes.<\/p>\n

(3) 0.012% w\/v of salbutamol sulfate BPCRS, 0.00005% w\/v of salbutamol ketone BPCRS (impurity J) and 0.00002% w\/v of salbutamol impurity Q BPCRS.<\/p>\n

(4) 0.012% w\/v of salbutamol for peak identification EPCRS.<\/p>\n

(5) 0.012% w\/v of salbutamol impurity standard BPCRS.<\/p>\n

(6) Dilute 1 volume of solution (2) to 5 volumes.<\/p>\n

CHROMATOGRAPHIC CONDITIONS<\/h4>\n

(a) Use a stainless steel column (15 cm \u00d7 4.6 mm) packed with base-deactivated end-capped octylsilyl silica gel for chromatography (3 \u03bcm) (Hypersil BDS C8 is suitable).<\/p>\n

(b) Use gradient elution and the mobile phase described below.<\/p>\n

(c) Use a flow rate of 1.0 mL per minute.<\/p>\n

(d) Use a column temperature of 30\u00b0.<\/p>\n

(e) Use a detection wavelength of 273 nm.<\/p>\n

(f) Inject 50 \u03bcL of each solution.<\/p>\n

MOBILE PHASE<\/h4>\n

Mobile phase A 0.5 volumes of triethylamine and 1000 volumes of 0.025M sodium dihydrogen orthophosphate, adjust to pH 3.0 with 10% v\/v of orthophosphoric acid.<\/p>\n

Mobile phase B 350 volumes of methanol and 650 volumes of acetonitrile.<\/p>\n\n\n\n\n\n\n\n\n\n\n
Time (Minutes)\u00a0<\/strong><\/td>\nMobile phase A (% v\/v)\u00a0<\/strong><\/td>\nMobile phase B (% v\/v)\u00a0<\/strong><\/td>\nComment<\/strong><\/td>\n<\/tr>\n
0-5<\/td>\n95<\/td>\n5<\/td>\nisocratic<\/td>\n<\/tr>\n
5-18<\/td>\n95\u219270<\/td>\n5\u219230<\/td>\nlinear gradient<\/td>\n<\/tr>\n
18-20<\/td>\n70<\/td>\n30<\/td>\nisocratic<\/td>\n<\/tr>\n
20-20.1<\/td>\n70\u219210<\/td>\n30\u219290<\/td>\nlinear gradient<\/td>\n<\/tr>\n
20.1-25<\/td>\n10<\/td>\n90<\/td>\nisocratic<\/td>\n<\/tr>\n
25-25.1<\/td>\n10\u219295<\/td>\n90\u21925<\/td>\nlinear gradient<\/td>\n<\/tr>\n
25.1-33<\/td>\n95<\/td>\n5<\/td>\nre-equilibration<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

SYSTEM SUITABILITY<\/h4>\n

The test is not valid unless: in the chromatogram obtained with solution (3), the peak-to-valley ratio is at least 6.0, where Hp is the height above the baseline of the peak due to impurity J and Hv is the height above the baseline of the lowest point of the curve separating this peak from the peak due to salbutamol;
\nin the chromatogram obtained with solution (6), the signal-to-noise ratio for the peak due to salbutamol is at least 20.<\/p>\n

CALCULATION OF IMPURITIES<\/h4>\n

For impurities J and Q, use the concentration of each impurity in solution (3).<\/p>\n

For all other impurities, use the concentration of salbutamol in solution (2).<\/p>\n

For the reporting threshold, use the concentration of salbutamol in solution (6). For impurity N, apply the reporting threshold to the sum of impurity N peaks 1 and 2.<\/p>\n

For peak identification, use solutions (3), (4) and (5).<\/p>\n

Salbutamol retention time: about 8 minutes.<\/p>\n

Relative retention: impurity J, about 0.95; impurity Q, about 1.4; impurity D, about 1.7; impurity N (peak 1), about 1.77; impurity N (peak 2), about 1.79; impurity F, about 1.9.<\/p>\n

Correction factors: impurity D, multiply by 1.5.<\/p>\n

LIMITS<\/h4>\n

\u2014 impurities D and F: for each impurity, not more than 0.5%;<\/p>\n

\u2014 impurities N (sum of peaks 1 and 2) and Q: for each impurity, not more than 0.2%;<\/p>\n

\u2014 unspecified impurities: for each impurity, not more than 0.2%;<\/p>\n

\u2014 total impurities: not more than 1.5%;<\/p>\n

\u2014 reporting threshold: 0.1%.<\/p>\n

Uniformity of delivered dose<\/h3>\n

Complies with the requirements stated under Pressurised Metered-dose Preparations for Inhalation using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.<\/p>\n

(1) Collect single doses of the preparation being examined using the procedure described under Pressurised Metered-dose Preparations for Inhalation, Uniformity of delivered dose and dissolve the collected dose in sufficient methanol to produce a solution containing the equivalent of 0.000075% w\/v of salbutamol.<\/p>\n

(2) 0.000092% w\/v of salbutamol sulfate BPCRS in methanol.<\/p>\n

CHROMATOGRAPHIC CONDITIONS<\/h4>\n

(a) Use a stainless steel column (10 cm \u00d7 3 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 \u03bcm) (Spherisorb ODS is suitable).<\/p>\n

(b) Use isocratic elution and the mobile phase described below.<\/p>\n

(c) Use a flow rate of 0.85 mL per minute.<\/p>\n

(d) Use a column temperature of 50\u00b0.<\/p>\n

(e) Use a detection wavelength of 276 nm.<\/p>\n

(f) Inject 150 \u03bcL of each solution.<\/p>\n

MOBILE PHASE<\/h4>\n

238 volumes of 0.1% w\/v of ammonium acetate solution and 762 volumes of methanol.<\/p>\n

When the chromatograms are recorded under the prescribed conditions, the retention time of salbutamol is about 2 minutes.<\/p>\n

SYSTEM SUITABILITY<\/h4>\n

The test is not valid, unless in the chromatogram obtained with solution (2), the symmetry factor for the peak due to salbutamol is between 0.8 to 2.5.<\/p>\n

DETERMINATION OF CONTENT<\/h4>\n

Calculate the content of salbutamol, C13<\/sub>H21<\/sub>NO3<\/sub>, per delivered dose using the declared content of C13<\/sub>H21<\/sub>NO3<\/sub> in salbutamol sulfate BPCRS. Repeat the procedure as described under Pressurised Metered-dose Preparations for Inhalation, Uniformity of delivered dose.<\/p>\n

ASSAY<\/h2>\n

Use the average of the individual results determined in the test for Uniformity of delivered dose.<\/p>\n

LABELLING<\/h2>\n

The quantity of active ingredient is stated in terms of the equivalent amount of salbutamol.<\/p>\n

IMPURITIES<\/h2>\n

The impurities limited by the requirements of this monograph include impurity C, D, F, J, K, M, N, O and Q listed under Salbutamol Sulfate and:<\/p>\n

\"Salbutamol<\/p>\n

1. 2,2-dihydroxy-1-[4-hydroxy-3-(hydroxymethyl)phenyl]ethanone (glyoxal impurity)<\/p>\n

\"Salbutamol<\/p>\n

2. 2-[4-hydroxy-3-(hydroxymethyl)benzyl]-4-{1-hydroxy-2-[(2-methyl-2-propanyl)amino]ethyl}phenol (head-to-tail dimer impurity).<\/p>\n","protected":false},"excerpt":{"rendered":"

Action and use Beta2-adrenoceptor agonist; bronchodilator. DEFINITION Salbutamol Pressurised Inhalation, Suspension is a suspension of Salbutamol Sulfate in a suitable liquid in a pressurised container fitted with a metering dose valve. The pressurised inhalation, suspension complies with the requirements stated under Preparations for Inhalation and with the following requirements. PRODUCTION The size of aerosol particles…<\/p>\n","protected":false},"author":4,"featured_media":20655,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[175],"tags":[],"class_list":["post-20624","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-formulated-preparations-specific-monographs"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/20624","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\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=20624"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/20624\/revisions"}],"predecessor-version":[{"id":20657,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/20624\/revisions\/20657"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/20655"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=20624"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=20624"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=20624"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}