Add the following:
Polyglyceryl Dioleate
R–O–(CH2–CH(OR)–CH2–O)3–R
R = H, or CO–C17H33
1,2,3-Propanetriol, homotrimer, di[(9Z)-9-octadecenoate];
Triglyceril dioleate;
Polyglyceryl 3 dioleate
[9007-48-1].R–O–(CH2–CH(OR)–CH2–O)6–R
R = H, or CO–C17H33
1,2,3-Propanetriol, homohexamer, di[(9Z)-9-octadecenoate];
Hexaglyceril dioleate;
Polyglyceryl 6 dioleate
[76009-37-5].DEFINITION
Polyglyceryl Dioleate is a mixture of polyglyceryl diesters of mainly oleic acid, obtained by esterification of polyglycerin and oleic acid. The polyglycerin consists mainly of triglycerin or hexaglycerin.
IDENTIFICATION
• B.
Meets the requirements of the test for Content of Fatty Acids
• C.
Meets the requirements of the test for Fats and Fixed Oils 
401
, Hydroxyl Value. [Note—This test will differentiate for Polyglyceryl 3 Dioleate and Polyglyceryl 6 Dioleate. ]
401, Hydroxyl Value. [Note—This test will differentiate for Polyglyceryl 3 Dioleate and Polyglyceryl 6 Dioleate. ]
ASSAY
• Content of Fatty Acids
0.5 N methanolic sodium hydroxide solution:
Dissolve 20 g of sodium hydroxide in 50 mL of water, and mix. Cool to room temperature, and add 950 mL of methanol.
Boron trifluoride methanol solution:
Dissolve 14 g of boron trifluoride in methanol to make 100 mL, and mix well.1
Saturated sodium chloride solution:
Dissolve about 375 g of sodium chloride in water to make 1000 mL.
Standard solution:
Prepare the calibration ester mixture by mixing up each individual ester component (see Table 1 for the component’s composition). Dissolve 500 mg of the calibration ester mixture in n-heptane, and dilute with n-heptane to 50 mL. [Note—Commercially available mixtures of fatty acid methyl esters may also be used. ]
Table 1
| Component in the Calibration Ester Mixture |
Composition (%) |
|---|---|
| USP Methyl Myristate RS (C14:0) | 5 |
| USP Methyl Palmitate RS (C16:0) | 15 |
| USP Methyl Palmitoleate RS (C16:1) | 10 |
| USP Methyl Stearate RS (C18:0) | 10 |
| USP Methyl Oleate RS (C18:1) | 20 |
| USP Methyl Linoleate RS (C18:2) | 15 |
| USP Methyl Linolenate RS (C18:3) | 10 |
| Methyl arachidate (C20:0) | 10 |
| Methyl gadoleate (C20:1) | 5 |
Sample solution:
Introduce 100 mg of Polyglyceryl Dioleate into a 25-mL conical flask fitted with a suitable water-cooled reflux condenser and a magnetic stir bar. Add 2 mL of 0.5 N methanolic sodium hydroxide solution, mix, and reflux for about 30 min. Add 2 mL of Boron trifluoride methanol solution through the condenser and reflux for about 30 min. Add 4 mL of n-heptane through the condenser, and reflux for 5 min. Cool, remove the condenser, add about 10 mL of Saturated sodium chloride solution, shake, add a quantity of Saturated sodium chloride solution to bring the upper layer up to the neck of the flask, and allow the layers to separate. Collect 2 mL of the n-heptane layer (upper layer), wash with three quantities, each at 2 mL of water, and dry the n-heptane phase over anhydrous sodium sulfate.
Chromatographic system
Mode:
GC
Detector:
Flame ionization
Column:
0.32-mm × 30-m fused-silica capillary; 0.25-µm layer of phase G16
Temperature
Detector:
250
Injection port:
240
Column:
See temperature program table below.
| Initial Temperature ( ) |
Temperature Ramp ( /min) |
Final Temperature ( ) |
Hold Time at Final Temperature (min) |
|---|---|---|---|
| 150 | 6 | 250 | 6 |
Carrier gas:
Nitrogen
Flow rate:
1.0–1.2 mL/min
Injection size:
1 µL
Injection type:
Split injection. The split ratio is about 1:80.
System suitability
Sample:
Standard solution
[Note—See the relative retention time table below. ]
| Component | Relative Retention Time |
|---|---|
| Methyl myristate | 0.74 |
| Methyl palmitate | 1.00 |
| Methyl palmitoleate | 1.03 |
| Methyl stearate | 1.29 |
| Methyl oleate | 1.33 |
| Methyl linoleate | 1.37a |
| Methyl linolenate | 1.46b |
| Methyl arachidate | 1.55 |
| Methyl gadoleate | 1.58 |
|
a
There could be an isomer eluting at a relative retention time of 1.39.
b
There could be two isomers eluting at relative retention times of 1.45 and 1.48.
|
|
Suitability requirements
Resolution:
NLT 1.5 between the peaks due to methyl stearate and methyl oleate
Relative standard deviation:
NMT 6.0% for the palmitate and stearate peak areas
Analysis
Samples:
Standard solution and Sample solution
Identify the fatty acid ester peaks of the Sample solution by comparing the retention times of these peaks with those of the Standard solution, and measure the peak areas for all of the fatty acid esters in the Sample solution.
Calculate the percentage of each fatty acid ester component in the test specimen:
Result = (A/B) × 100
| A | = | = peak area of each individual fatty acid ester component |
| B | = | = sum of the peak areas, excluding the solvent peak, of the Sample solution |
Acceptance criteria:
Polyglyceryl Dioleate exhibits the following composition profile of fatty acids.
5.0IMPURITIES
Inorganic Impurities
• Residue on Ignition
Analysis:
Heat a silica crucible to redness for 30 min, allow to cool in a desiccator, and weigh. Evenly distribute about 1.0 g of Polyglyceryl Dioleate in the crucible, and weigh. Dry at 100–105 for 1 h, and ignite in a muffle furnace at 600 ± 25, until the test substance is thoroughly charred. Perform the test for Residue on Ignition 281 on the residue obtained, starting with “Moisten the sample with a small amount (usually 1 mL) of sulfuric acid.”
–105 for 1 h, and ignite in a muffle furnace at 600 ± 25, until the test substance is thoroughly charred. Perform the test for Residue on Ignition 281 on the residue obtained, starting with “Moisten the sample with a small amount (usually 1 mL) of sulfuric acid.”
Acceptance criteria:
NMT 1%
• Heavy Metals, Method II 231:
NMT 10 ppm
231:
NMT 10 ppm
SPECIFIC TESTS
• Acid Value
Analysis:
Accurately weigh (to within 0.1 mg) 5–10 g of Polyglyceryl Dioleate, add 10 mL of alcohol and 3 drops of phenolphthalein TS, and titrate with 0.1 N potassium hydroxide VS or 0.1 N sodium hydroxide VS until the solution remains faintly pink after shaking for 30 s. Proceed as directed in Fats and Fixed Oils 401, Acid Value to perform the calculation.
401, Acid Value to perform the calculation.
Acceptance criteria
Polyglyceryl 3 dioleate:
NMT 6
Polyglyceryl 6 dioleate:
NMT 6
• Fats and Fixed Oils, Hydroxyl Value 401
401
Acceptance criteria
Polyglyceryl 3 dioleate:
195–245, determined on a 0.7-g to 1.0-g specimen
Polyglyceryl 6 dioleate:
270–320, determined on 0.5-g to 0.7-g specimen
• Iodine Value
Analysis:
Accurately weigh 0.15 g of Polyglyceryl Dioleate, transfer to a dry 250-mL flask with a ground-glass stopper, and add 25 mL of methylene chloride. Add 20 mL of the Wijs’ solution.2 Close the flask, and keep it in the dark for 1 h while shaking frequently. Perform the test in Fats and Fixed Oils 401, Iodine Value, starting with “Then add, in the order named, 30 mL of potassium iodide TS and 100 mL of water.”
401, Iodine Value, starting with “Then add, in the order named, 30 mL of potassium iodide TS and 100 mL of water.”
Acceptance criteria
Polyglyceryl 3 dioleate:
60–80
Polyglyceryl 6 dioleate:
50–70
• Fats and Fixed Oils, Peroxide Value 401:
Use 30 mL of a mixture of glacial acetic acid and methylene chloride (3:2) to replace 30 mL of a mixture of glacial acetic acid and chloroform (3:2).
401:
Use 30 mL of a mixture of glacial acetic acid and methylene chloride (3:2) to replace 30 mL of a mixture of glacial acetic acid and chloroform (3:2).
Acceptance criteria
Polyglyceryl 3 dioleate:
NMT 12.5
Polyglyceryl 6 dioleate:
NMT 12.5
• Fats and Fixed Oils, Saponification Value 401:
Determined on 1-g specimen
401:
Determined on 1-g specimen
Acceptance criteria
Polyglyceryl 3 dioleate:
135–155
Polyglyceryl 6 dioleate:
110–140
• Water, Method I 921:
NMT 1%, determined on a 2.0-g specimen
921:
NMT 1%, determined on a 2.0-g specimen
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers, protected from heat and moisture.
• Labeling:
Label to indicate whether it is Polyglyceryl 3 Dioleate or Polyglyceryl 6 Dioleate.
• USP Reference Standards 11
11
USP Methyl Linoleate RS
USP Methyl Linolenate RS
USP Methyl Myristate RS
USP Methyl Oleate RS
USP Methyl Palmitate RS
USP Methyl Palmitoleate RS
USP Methyl Stearate RS
USP Polyglyceryl 3 Dioleate RS
USP Polyglyceryl 6 Dioleate RS
NF30
1
Boron trifluoride–methanol solution (14% in methanol) is also commercially available from Sigma, B-1252, or equivalent quality.
2
Wijs’ reagent RPE for analysis from Carlo Erba Reference 491902; Wijs’ solution from www.sigmaaldrich.com, or equivalent quality.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Hong Wang, Ph.D.
Senior Scientific Liaison 1-301-816-8351 |
(EXC2010) Monographs - Excipients |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 1907
Pharmacopeial Forum: Volume No. 36(5) Page 1234