Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n
Preparation<\/strong><\/p>\n Paediatric Vitamins A, C and D Oral Drops<\/p>\n Vitamin A Refers to a number of substances of very similar structure (including (Z)-isomers) found in animal tissues and possessing similar activity. The principal and biologically most active substance is all-(E)-retinol (all-(E)-3,7-dimethyl-9- (2,6,6-trimethylcyclohex-1-enyl)nona-2,4,6,8-tetraen-1-ol; C20H30O). Vitamin A is generally used in the form of esters such as the acetate, propionate and palmitate.<\/p>\n Synthetic retinol ester\u00a0 Refers to an ester (acetate, propionate or palmitate) or a mixture of synthetic retinol esters.<\/p>\n The activity of vitamin A is expressed in retinol equivalents (R.E.). 1 mg R.E. corresponds to the activity of 1 mg of all-(E)- retinol. The activity of the other retinol esters is calculated stoichiometrically, so that 1 mg R.E. of vitamin A corresponds to the activity of:<\/p>\n \u2014 1.147 mg of all-(E)-retinol acetate,<\/p>\n \u2014 1.195 mg of all-(E)-retinol propionate,<\/p>\n \u2014 1.832 mg of all-(E)-retinol palmitate.<\/p>\n International Units (IU) are also used to express the activity of vitamin A. 1 IU of vitamin A is equivalent to the activity of 0.300 \u00b5g of all-(E)-retinol. The activity of the other retinol esters is calculated stoichiometrically, so that 1 IU of vitamin A is equivalent to the activity of:<\/p>\n \u2014 0.344 \u00b5g of all-(E)-retinol acetate,<\/p>\n \u2014 0.359 \u00b5g of all-(E)-retinol propionate,<\/p>\n \u2014 0.550 \u00b5g of all-(E)-retinol palmitate,<\/p>\n 1 mg of retinol equivalent is equivalent to 3333 IU.<\/p>\n Retinol acetate: pale-yellow crystals (mp: about 60 \u00b0C). Once melted retinol acetate tends to yield a supercooled melt. Retinol propionate: reddish-brown oily liquid.<\/p>\n Retinol palmitate: a fat-like, light yellow solid or a yellow oily liquid, if melted (mp: about 26 \u00b0C).<\/p>\n All retinol esters are practically insoluble in water, soluble or partly soluble in anhydrous ethanol and miscible with organic solvents.<\/p>\n Vitamin A and its esters are very sensitive to the action of air, oxidising agents, acids, light and heat.<\/p>\n Carry out the assay and all tests as rapidly as possible, avoiding exposure to actinic light and air, oxidising agents, oxidation catalysts (e.g. copper, iron), acids and heat; use freshly prepared solutions.<\/p>\n A. Thin-layer chromatography (2.2.27).<\/p>\n Test solution\u00a0 Prepare a solution containing about 3.3 IU of vitamin A per microlitre in cyclohexane R containing 1 g\/L of butylhydroxytoluene R.<\/p>\n Reference solution\u00a0 Prepare a 10 mg\/mL solution of retinol esters CRS (i.e. 3.3 IU of each ester per microlitre) in cyclohexane R containing 1 g\/L of butylhydroxytoluene R. Plate TLC silica gel F254 plate R.<\/p>\n Mobile phase ether R, cyclohexane R (20:80 V\/V). Application 3 \u00b5L.<\/p>\n Development\u00a0 Over 2\/3 of the plate.<\/p>\n Drying\u00a0 In air.<\/p>\n Detection\u00a0 Examine in ultraviolet light at 254 nm.<\/p>\n System suitability\u00a0 Reference solution:<\/p>\n \u2014 the chromatogram shows the individual spots of the corresponding esters. The elution order from bottom to top is: retinol acetate, retinol propionate and retinol palmitate.<\/p>\n Results The composition of esters is confirmed by the correspondence of the principal spot or spots of the test solution with those obtained with the reference solution.<\/p>\n B. Related substances (see Tests).<\/p>\n Thin-layer chromatography (2.2.27).<\/p>\n Test solution Prepare a solution in cyclohexane R, stabilised with a solution containing 1 g\/L of butylhydroxytoluene R, containing about 330 IU of vitamin A per microlitre.<\/p>\n Reference solution Shake 1 mL of the test solution with 20 mL of 0.1 M tetrabutylammonium hydroxide in 2-propanol for 2 min and dilute to 100 mL with cyclohexane R, stabilised with a solution containg 1 g\/L of butylhydroxytoluene R.<\/p>\n Plate\u00a0 TLC silica gel F254 plate R.<\/p>\n Mobile phase ether R, cyclohexane R (20:80 V\/V). Application 3 \u00b5L.<\/p>\n Development\u00a0 Over a path of 15 cm.<\/p>\n Drying\u00a0 In air.<\/p>\n Detection\u00a0 Examine in ultraviolet light at 254 nm.<\/p>\n System suitability\u00a0 Reference solution:<\/p>\n \u2014 in the chromatogram obtained no or only traces of the retinol esters are seen.<\/p>\n Limit Any spot corresponding to retinol in the chromatogram obtained with the test solution is not more intense than the spot in the chromatogram obtained with the reference solution (1.0 per cent).<\/p>\n Ultraviolet and visible absorption spectrophotometry (2.2.25).<\/p>\n Test solution\u00a0 The solution described under Activity.<\/p>\n Absorption maximum\u00a0 At 325 nm to 327 nm.<\/p>\n Absorbance ratios:<\/p>\n \u2014 A300\/A326 = maximum 0.60;<\/p>\n \u2014 A350\/A326 = maximum 0.54;<\/p>\n \u2014 A370\/A326 = maximum 0.14.<\/p>\n The thresholds indicated under Related substances (Table 2034.-1) in the general monograph Substances for pharmaceutical use (2034) do not apply.<\/p>\n The activity of the substance is determined in order to be taken into account for the production of concentrates.<\/p>\n Dissolve 25-100 mg, weighed with an accuracy of 0.1 per cent, in 5 mL of pentane R and dilute with 2-propanol R1 to a presumed concentration of 10 IU\/mL to 15 IU\/mL. Measure the absorbance (2.2.25) at the absorption maximum at 326 nm. Calculate the activity of vitamin A in International Units per gram from the expression:<\/p>\n (A326<\/sub>\u00d7V \u00d71900)\/(100\u00d7m)<\/p>\n A326<\/sub> = absorbance at 326 nm,<\/p>\n m = mass of the substance to be examined, in grams,<\/p>\n V = total volume to which the substance to be examined is diluted to give 10 IU\/mL to 15 IU\/mL,<\/p>\n 1900 = factor to convert the specific absorbance of esters of retinol into International Units per gram.<\/p>\n In an airtight container, protected from light.<\/p>\n Once the container has been opened, its contents are to be used as soon as possible; any part of the contents not used at once should be protected by an atmosphere of inert gas.<\/p>\n The label states:<\/p>\n \u2014 the number of International Units per gram,<\/p>\n \u2014 the name of the ester or esters.<\/p>\n A. R = H, CO-CH3: kitols (Diels-Alder dimers of vitamin A),<\/p>\n B. (3E,5E,7E)-3,7-dimethyl-9-[(1Z)-2,6,6-trimethylcyclohex-2-enylidene]nona-1,3,5,7-tetraene (anhydro-vitamin A),<\/p>\n C. (3E,5E,7E)-3,7-dimethyl-9-[(1Z)-2,6,6-trimethylcyclohex-2-enylidene]nona-3,5,7-trien-1-ol (retro-vitamin A),<\/p>\n D. oxidation products of vitamin A.<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Preparation Paediatric Vitamins A, C and D Oral Drops DEFINITION Vitamin A Refers to a number of substances of very similar structure (including (Z)-isomers) found in animal tissues and possessing similar activity. The principal and biologically most active substance is all-(E)-retinol (all-(E)-3,7-dimethyl-9- (2,6,6-trimethylcyclohex-1-enyl)nona-2,4,6,8-tetraen-1-ol; C20H30O). Vitamin A is generally…<\/p>\n","protected":false},"author":5,"featured_media":31487,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-31486","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\/31486","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\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=31486"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/31486\/revisions"}],"predecessor-version":[{"id":31491,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/31486\/revisions\/31491"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/31487"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=31486"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=31486"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=31486"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}DEFINITION<\/h2>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
Solubility<\/h3>\n
IDENTIFICATION<\/h2>\n
TESTS<\/h2>\n
Retinol<\/h3>\n
Related substances<\/h3>\n
ACTIVITY<\/h2>\n
STORAGE<\/h2>\n
LABELLING<\/h2>\n
IMPURITIES<\/h2>\n