Accessed from 10.6.1.1 by correct6 on Wed Apr 15 13:21:49 EDT 2015
6136 Polysorbate / Official Monographs
NF 32
• USP REFERENCE STANDARDS 〈11〉
USP Polysorbate 20 RS
•
•
.
Polysorbate 40
The ratio of OH group to C15H31COO group is mainly 3:1.
Polyethylene glycol 20 sorbitan ether monopalmitate;
Polyoxyethylene 20 sorbitan monohexadecanoate;
Polyoxyethylene 20 sorbitan monopalmitate [9005-66-7].
DEFINITION
Polysorbate 40 is a palmitate ester of sorbitol and its anhydrides copolymerized with about 20 moles of ethylene oxide for each mole of sorbitol and sorbitol anhydrides. The
fatty acids may be of vegetable, animal, or synthetic
origin.
IDENTIFICATION
• A. INFRARED ABSORPTION 〈197F〉
• B. It meets the requirements in the Assay for Composition
of Fatty Acids.
ASSAY
• COMPOSITION OF FATTY ACIDS
Polysorbate 40 exhibits the composition profiles of fatty
acids shown in Table 1, as determined in Fats and Fixed
Oils 〈401〉, Fatty Acid Composition.
Table 1
NF Monographs
Carbon-Chain
Length
16
Number of
Double Bonds
0
•
•
the mouth of the flask, cool under running water, and
add 5 drops of phenolphthalein TS. Titrate with 0.1 N
sodium hydroxide VS. Calculate the acid value as directed in the chapter.
Acceptance criteria: NMT 2.0
FATS AND FIXED OILS, Hydroxyl Value 〈401〉: 89–105
FATS AND FIXED OILS, Peroxide Value 〈401〉
Sample: 10.0 g
Saturated potassium iodide solution: Prepare a saturated solution of potassium iodide in carbon dioxidefree water. Make sure the solution remains saturated as
indicated by the presence of undissolved crystals.
Analysis: Introduce the Sample into a 100-mL beaker,
and dissolve with 20 mL of glacial acetic acid. Add 1 mL
of Saturated potassium iodide solution, mix, and allow to
stand for 1 min. Add 50 mL of carbon dioxide-free
water and a magnetic stirring bar. Titrate with 0.01 M
sodium thiosulfate VS, determining the endpoint potentiometrically (see Titrimetry 〈541〉). Perform a blank
titration.
Calculate the peroxide value as directed in the chapter.
Acceptance criteria: NMT 10.0
For Polysorbate 40 intended for use in the manufacture of injectable dosage forms: NMT 5.0
FATS AND FIXED OILS, Saponification Value 〈401〉: 41–52
WATER DETERMINATION, Method I 〈921〉: NMT 3.0%
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight containers,
protected from light and moisture. Store at room temperature.
• LABELING: Label it to indicate whether the fatty acids are
derived from animal, vegetable, or synthetic sources.
Where Polysorbate 40 is intended for use in the manufacture of injectable dosage forms, it is so labeled.
• USP REFERENCE STANDARDS 〈11〉
USP Polysorbate 40 RS
.
Polysorbate 60
Percentage
(%)
≥92.0
IMPURITIES
• RESIDUE ON IGNITION 〈281〉: NMT 0.25%
• HEAVY METALS, Method II 〈231〉: NMT 10 ppm
• ETHYLENE OXIDE AND DIOXANE, Method II 〈228〉
Acceptance criteria
Ethylene oxide: NMT 1 ppm
Dioxane: NMT 10 ppm
SPECIFIC TESTS
• BACTERIAL ENDOTOXINS TEST 〈85〉
For Polysorbate 40 intended for use in the manufacture of injectable dosage forms: The level of bacterial
endotoxins is such that the requirement in the relevant
dosage form monograph(s) in which Polysorbate 40 is
used can be met. Where the label states that Polysorbate 40 must be subjected to further processing during
the preparation of injectable dosage forms, the level of
bacterial endotoxins is such that the requirement in the
relevant dosage form monograph(s) in which Polysorbate 40 is used can be met.
• FATS AND FIXED OILS, Acid Value 〈401〉
Sample: 10.0 g
Analysis: Transfer the Sample to a wide-mouth, 250-mL
conical flask, and add 50 mL of neutralized alcohol.
Heat on a steam bath nearly to boiling, shaking thoroughly occasionally while heating. Invert a beaker over
The ratio of OH group to the sum of C15H31COO and
C17H35COO groups is mainly 3:1.
Polyethylene glycol 20 sorbitan ether monostearate;
Polyoxyethylene 20 sorbitan monooctadecanoate;
Polyoxyethylene 20 sorbitan monostearate [9005-67-8].
DEFINITION
Polysorbate 60 is a mixture of stearate and palmitate esters
of sorbitol and its anhydrides copolymerized with about
20 moles of ethylene oxide for each mole of sorbitol and
sorbitol anhydrides. The fatty acids may be of vegetable,
animal, or synthetic origin.
IDENTIFICATION
• A. INFRARED ABSORPTION 〈197F〉
• B. It meets the requirements in the Assay for Composition
of Fatty Acids.
Official from December 1, 2014
Copyright (c) 2015 The United States Pharmacopeial Convention. All rights reserved.
Accessed from 10.6.1.1 by correct6 on Wed Apr 15 13:21:49 EDT 2015
NF 32
Official Monographs / Polysorbate 6137
ASSAY
• COMPOSITION OF FATTY ACIDS
Polysorbate 60 exhibits the composition profiles of fatty
acids shown in Table 1, as determined in Fats and Fixed
Oils 〈401〉, Fatty Acid Composition.
Table 1
Carbon-Chain
Number of
Length
Double Bonds
18
0
Sum of stearic acid (C18:0)
and palmitic acid (C16:0)
Percentage
(%)
40.0–60.0
EP
+
+
+
+
+
+
+
+
JP
+
+
+
+
+
+
+
+
USP
+
+
+
+
+
+
+
+
Legend: + will adopt and implement; − will not stipulate
Nonharmonized attributes: Characters, Identification by IR
(EP), Heavy Metals (USP)
Each pharmacopeia will adapt the text to take account of
local reference substances and spectra and reagent
specifications.
Sorbitan, mono-9-octadecenoate, poly(oxy-1,2-ethanediyl)
derivs., (Z)-;
Polyoxyethylene 20 sorbitan monooleate [9005-65-6].
≥90.0
IMPURITIES
• RESIDUE ON IGNITION 〈281〉: NMT 0.25%
• HEAVY METALS, Method II 〈231〉: NMT 10 ppm
• ETHYLENE OXIDE AND DIOXANE, Method II 〈228〉
Acceptance criteria
Ethylene oxide: NMT 1 ppm
Dioxane: NMT 10 ppm
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight containers,
protected from light and moisture. Store at room temperature.
• LABELING: Label to indicate whether the fatty acids are
derived from animal, vegetable, or synthetic sources.
• USP REFERENCE STANDARDS 〈11〉
USP Polysorbate 60 RS
.
Polysorbate 80
EP
+
+
JP
+
+
USP
+
+
+
+
+
DEFINITION
Polysorbate 80 is a mixture of partial esters of fatty acids,
mainly oleic acid, with sorbitol and its anhydrides ethoxylated with approximately 20 moles of ethylene oxide for
each mole of sorbitol and sorbitol anhydrides.
IDENTIFICATION
• It complies with the test for Composition of Fatty Acids.
ASSAY
• COMPOSITION OF FATTY ACIDS
Diluent: 20 g/L of sodium hydroxide in methanol
Saturated sodium chloride solution: Sodium chloride
and water (1:2). Before use, decant the solution from
any undissolved substance and filter, if necessary.
Reference solution A: Prepare 0.50 g of the mixture of
calibrating substances with the composition described
in Table 1. Dissolve in heptane, and dilute with heptane
to 50.0 mL.
Reference solution B: Reference solution A in heptane
(1 in 10)
Reference solution C: Prepare 0.50 g of a mixture of
fatty acid methyl esters, which corresponds to the composition of the substance to be examined. Dissolve in
heptane, and dilute with heptane to 50.0 mL. [NOTE—
Commercially available mixtures of fatty acid methyl esters may also be used.]
Sample solution: Dissolve 0.10 g of Polysorbate 80 in
2 mL of Diluent in a 25-mL conical flask, and boil under
a reflux condenser for 30 min. Add 2.0 mL of 14% boron trifluoride–methanol through the condenser, and
boil for 30 min. Add 4 mL of heptane through the condenser, and boil for 5 min. Cool and add 10.0 mL of
Saturated sodium chloride solution, shake for about 15 s,
and add a quantity of Saturated sodium chloride solution
such that the upper phase is brought into the neck of
the flask. Collect 2 mL of the upper phase, wash with
three quantities, each of 2 mL, of water, and dry over
anhydrous sodium sulfate.
Table 1
Mixture of the Following
Substances
Methyl myristate
Methyl palmitate
Methyl stearate
Methyl arachidate
Methyl oleate
Methyl eicosenoate
Methyl behenate
Methyl lignocerate
Composition (%)
5
10
15
20
20
10
10
10
Official from December 1, 2014
Copyright (c) 2015 The United States Pharmacopeial Convention. All rights reserved.
NF Monographs
SPECIFIC TESTS
• FATS AND FIXED OILS, Acid Value 〈401〉
Sample: 10.0 g of Polysorbate 60
Analysis: Transfer the Sample to a wide-mouth, 250-mL
conical flask, and add 50 mL of neutralized alcohol.
Heat on a steam bath nearly to boiling, shaking thoroughly occasionally while heating. Invert a beaker over
the mouth of the flask, cool under running water, and
add 5 drops of phenolphthalein TS. Titrate with 0.1 N
sodium hydroxide VS. Calculate the acid value as directed in the chapter.
Acceptance criteria: NMT 2.0
• FATS AND FIXED OILS, Hydroxyl Value 〈401〉: 81–96
• FATS AND FIXED OILS, Peroxide Value 〈401〉
Sample: 10.0 g
Saturated potassium iodide solution: Prepare a saturated solution of potassium iodide in carbon dioxidefree water. Make sure the solution remains saturated as
indicated by the presence of undissolved crystals.
Analysis: Introduce the Sample into a 100-mL beaker,
and dissolve with 20 mL of glacial acetic acid. Add 1 mL
of Saturated potassium iodide solution, mix, and allow to
stand for 1 min. Add 50 mL of carbon dioxide-free
water and a magnetic stirring bar. Titrate with 0.01 M
sodium thiosulfate VS, determining the endpoint potentiometrically (see Titrimetry 〈541〉). Perform a blank
titration.
Calculate the peroxide value as directed in the chapter.
Acceptance criteria: NMT 10.0
• FATS AND FIXED OILS, Saponification Value 〈401〉: 45–55
• WATER DETERMINATION, Method I 〈921〉: NMT 3.0%
Attributes
Definition
Identification (Composition of Fatty
Acids)
Acid Value
Attributes
Hydroxyl Value
Peroxide Value
Saponification Value
Composition of Fatty Acids
Ethylene Oxide and Dioxane
Water
Residue on Ignition
Storage