Caprylocaproyl Polyoxylglycerides
(kap ril'' oh kap' roil pol'' ee ox'' il glis' er ides).
Former title:Caprylocaproyl Macrogolglycerides
» Caprylocaproyl Polyoxylglycerides is a mixture of monoesters, diesters, and triesters of glycerol and monoesters and diesters of polyethylene glycols. The polyethylene glycols used have a mean molecular weight between 200 and 400. It is produced by partial alcoholysis of medium-chain triglycerides with polyethylene glycol, by esterification of glycerol and polyethylene glycol with caprylic acid and capric acid, or as a mixture of glycerol esters and ethylene oxide condensate with caprylic acid and capric acid. It may contain free polyethylene glycols.
Packaging and storage— Preserve in tight containers, protected from light and moisture. Store at controlled room temperature.
Labeling— Label it to indicate the type and the average nominal molecular weight of polyethylene glycol used, as part of the official title.
USP Reference standards 11
USP Caprylocaproyl Polyoxylglycerides RS
Identification—
B: Thin-Layer Chromatographic Identification Test 201
Test solution: 50 mg per mL in methylene chloride.
Standard solution: 50 mg per mL of USP Caprylocaproyl Polyoxylglycerides RS in methylene chloride.
Application volume: 50 µL.
Developing solvent system: a mixture of ether and hexanes (7:3).
Spray reagent— Prepare 0.1 mg per mL of solution of rhodamine B in alcohol.
Procedure— Proceed as directed in the chapter. Then spray the plate with Spray reagent, and locate the spots on the plate by examination under UV light at a wavelength of 365 nm: the RF values of the principle spots obtained from the Test solution correspond to those obtained from the Standard solution.
C: It meets the requirements of the test for Fatty acid composition.
Acid value 401: not more than 2.0, determined on a 2.0-g specimen.
Hydroxyl value 401 The hydroxyl value is within the range specified in Table 1 for the labeled type, when determined on a 1.0-g specimen, accurately weighed.
Table 1
Type of Polyethylene
Glycol
Hydroxyl Value
200 80–120
300 140–180
400 170–205
Iodine value 401: not more than 2.0.
Peroxide value 401: not more than 6.0, determined on a 2.0-g specimen.
Saponification value 401 The saponification value is within the range specified in Table 2 for the labeled type, determined on a 2.0-g specimen.
Table 2
Type of Polyethylene
Glycol
Saponification Value
200 265–285
300 170–190
400 85–105
Fatty acid composition 401 Caprylocaproyl Polyoxylglycerides exhibits the following composition profile of fatty acids, as determined in the section Fatty Acid Composition under Fats and Fixed Oils 401 (See Table 3.):
Table 3
Carbon-Chain
Length
Number of Double
Bonds
Percentage (%)
6 0 2.0
8 0 50.0–80.0
10 0 20.0–50.0
12 0 3.0
14 0 1.0
Water, Method I 921: not more than 1.0%, determined on a 1.0-g specimen. Instead of using methanol as the solvent, two solvent systems can be used: a mixture of anhydrous methanol and methylene chloride (3:7 (v/v)) or anhydrous pyridine.
Total ash 561: not more than 0.1%.
Heavy metals, Method II 231: not more than 0.001%.
Alkaline impurities— Weigh 5.0 g of Caprylocaproyl Polyoxylglycerides, add 10 mL of alcohol and 0.05 mL of bromophenol blue TS, and mix well. Titrate with 0.01 N hydrochloric acid VS to change the color to yellow: not more than 1.0 mL of 0.01 N hydrochloric acid is required.
Limit of free ethylene oxide and dioxane—
[Caution—Ethylene oxide is toxic and flammable. Prepare all solutions in a well-ventilated hood. The operator must protect hands and face by wearing polyethylene protective gloves and an appropriate face mask. Store all solutions in hermetic containers, and refrigerate at a temperature between 4 and 8. ]
[note—Perform all determinations three times. ]
Ethylene oxide stock solution— Into a dry, clean test tube, cooled in a mixture of 1 part of sodium chloride and 3 parts of crushed ice, introduce a slow current of ethylene oxide gas, allowing condensation onto the inner wall of the test tube. Using a glass syringe, previously cooled to 10, transfer about 300 µL of liquid ethylene oxide, equivalent to about 0.25 g, to 50 mL of polyethylene glycol 200. Determine the absorbed quantity of ethylene oxide by weighing before and after absorption. Dilute with polyethylene glycol 200 to 100.0 mL, and mix. This is the Ethylene oxide stock solution.
Transfer 10.0 mL of magnesium chloride solution, prepared by adding 5 g of magnesium chloride to 10 mL of alcohol, to a volumetric flask. Add 20.0 mL of 0.1 M alcoholic hydrochloric acid VS. Insert the stopper, shake to obtain a saturated solution, and allow to equilibrate overnight. Transfer 5.00 mL of Ethylene oxide stock solution, accurately measured, to the flask, and allow to stand for 30 minutes. Titrate with 0.1 M alcoholic potassium hydroxide VS, determining the endpoint potentiometrically. Perform a blank titration, using the same quantity of polyethylene glycol 200 instead of Ethylene oxide stock solution, and note the difference in volumes required. Each mL of the difference in volumes of 0.1 M alcoholic potassium hydroxide VS consumed is equivalent to 4.404 mg of ethylene oxide. Calculate the concentration of ethylene oxide, in mg per g, in the Ethylene oxide stock solution.
Ethylene oxide solution— Quantitatively dilute a volume of Ethylene oxide stock solution, accurately measured, with polyethylene glycol 200 to obtain a solution containing about 50 µg of ethylene oxide per g. Dilute 1.0 mL of this solution with water to 5.0 mL to obtain a solution having a known concentration of about 10 µg of ethylene oxide per mL. [note—Prepare immediately before use. ]
Dioxane stock solution— Dissolve about 1.00 g of dioxane, accurately weighed, in water, and dilute quantitatively, and stepwise if necessary, with water to obtain a solution having a known concentration of about 1.0 mg per mL.
Dioxane solution— Quantitatively dilute a volume of the Dioxane stock solution, accurately measured, with water to obtain a solution having a known concentration of about 0.5 mg of dioxane per mL.
Standard solution 1— Transfer about 1.0 g of the substance under test, accurately weighed, to a 10-mL vial, and add 1.0 mL of N,N-dimethylacetamide, 0.1 mL of Ethylene oxide solution, and 0.1 mL of Dioxane solution. Close the vial, and mix to obtain a homogenous solution. Allow to stand at 90 for 45 minutes.
Standard solution 2— Transfer 0.1 mL of Ethylene oxide solution to a 10-mL vial, add 0.1 mL of a freshly prepared solution of acetaldehyde, containing about 10 mg of acetaldehyde per L, and add 0.1 mL of Dioxane solution. Close the vial, and mix to obtain a homogenous solution.
Test solution— Transfer about 1.0 g of the substance under test, accurately weighed, to a 10-mL vial, and add 1.0 mL of N,N-dimethylacetamide and 0.2 mL of water. Close the vial, and mix to obtain a homogenous solution. Allow to stand at 90 for 45 minutes.
Chromatographic system (see Chromatography 621)— [note—Headspace apparatus that automatically transfers a measured amount of headspace may be used. ] The gas chromatograph is equipped with a flame-ionization detector and contains a 0.32-mm × 30-m glass or quartz capillary column bonded with a 1.0-µm layer of phase G1. The carrier gas is helium, flowing at a rate of about 1 mL per minute. The detector and injection port temperatures are maintained at 250 and 150, respectively. The column temperature is programmed as follows. Initially it is maintained at 50 for 5 minutes after injection, then increased to 180 at a rate of 5 per minute, further increased to 230 at a rate of 30 per minute, and maintained at this temperature for 5 minutes. Chromatograph the gaseous phase of Standard solution 2, and record the peak responses as directed for Procedure, adjusting the sensitivity of the system so that the peak heights of the two principal peaks in the chromatogram are not less than 15% of the full scale of the recorder: the relative retention times are about 0.94 for acetaldehyde and 1.0 for ethylene oxide; the resolution, R, between acetaldehyde and ethylene oxide is not less than 2.0; and the relative standard deviation for replicate injections is not more than 15.0%.
Procedure— Using a heated, gas-tight gas chromatographic syringe, separately inject equal volumes (about 1 mL) of the gaseous headspace of Standard solution 1 and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses: the mean areas of the ethylene oxide and dioxane peaks in the chromatogram obtained from the Test solution are not greater than half the mean areas of the corresponding peaks in the chromatogram obtained from Standard solution 1, equivalent to about 1 µg of ethylene oxide per g and 50 µg of dioxane per g. Calculate the concentration of ethylene oxide, in µg per g, in the test specimen taken by the formula:
CrU /(rS MU rU MS)
in which C is the concentration, in µg per mL, of ethylene oxide in Standard solution 1; rU and rS are the peak responses of ethylene oxide obtained from the Test solution and Standard solution 1, respectively; and MU and MS are the quantities, in g, of the substance under test taken to prepare the Test solution and Standard solution 1, respectively: not more than 1 µg per g is found. Calculate the concentration of dioxane, in µg per g, in the test specimen taken by the formula:
CD dU / 5(dS MU dU MS)
in which CD is the concentration, in µg, of dioxane in Standard solution 1; dU and dS are the peak responses of dioxane obtained from the Test solution and Standard solution 1, respectively; and MU and MS are as defined above: not more than 10 µg per g is found.
Limit of free glycerol— Dissolve 1.20 g of the substance under test in 25 mL of methylene chloride, heating if necessary. Cool, and add 100 mL of water and 25.0 mL of periodic acetic acid solution, prepared by dissolving 0.446 g of sodium periodate in 2.5 mL of a 25% (v/v) solution of sulfuric acid, and diluting to 100.0 mL with glacial acetic acid. Shake, and allow to stand for 30 minutes. Add 40 mL of potassium iodide solution, prepared by dissolving 3 g of potassium iodide in 40 mL of water, and allow to stand for 1 minute. Add 1 mL of starch TS, and titrate the liberated iodine with 0.1 M sodium thiosulfate. Perform a blank determination, and make any necessary correction (see Titrimetry 541). Each mL of 0.1 M sodium thiosulfate is equivalent to 2.3 mg of glycerol: not more than 5.0% is found.
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