»Glyceryl Distearate is a mixture of diglycerides,mainly glyceryl distearate,together with variable quantities of monoglycerides and triglycerides.It contains not less than 8.0percent and not more than 22.0percent of monoglycerides,not less than 40.0percent and not more than 60.0percent of diglycerides,and not less than 25.0percent and not more than 35.0percent of triglycerides.It is obtained by partial glycerolysis of vegetable oil that consists mainly of triglycerides of palmitic or stearic acid or by esterification of glycerol with stearic acid.The fatty acids may be of vegetable or animal origin.
Packaging and storage Preserve in tight containers.Store at room temperature.Protect from light,freezing,and excessive heat.
USP Reference standards á11ñ USP Glyceryl Distearate RS.
A: It meets the requirements of the test for Melting range.
B: Thin-Layer Chromatographic Identification Test á201ñ
Test solution: a solution in methylene chloride containing about 50mg per mL.
Developing solvent: a mixture of ether and hexane (70:30).
Spray reagent: a solution containing 20mg of rhodamine Bin 200mLof alcohol.
Procedure Proceed as directed in the chapter.Spray with the Spray reagent,and locate the spots on the plate by examination under UVlight at a wavelength of 365nm:the principal spot obtained from the Test solutioncorresponds in color,size,and RFvalue to that obtained from the Standard solution.
Melting range,Class IIá741ñ: between 50and 70.
Acid value á401ñ: not more than 6.0,determined on 1.0g,using a mixture of alcohol and toluene (1:1,v/v)as the solvent and with gentle heating.
Iodine value á401ñ: not more than 3.0.
Saponification value á401ñ: between 165and 195,determined on 2.0g;carry out the titration with heating.
Fatty acid composition á401ñ The fatty acid fraction of it contains not less than 40.0%of stearic acid;and the sum of the contents of palmitic and stearic acids,determined as directed in the chapter,is not less than 90.0%.
Water,Method Iá921ñ: not more than 1.0%,using pyridine in place of methanol in the titration vessel.
Total ash á561ñ: not more than 0.1%.
Limit of nickel [CautionWhen using closed high-pressure digestion vessels and microwave laboratory equipment,be familiar with the safety and operating instructions given by the manufacturer.]
Magnesium nitrate solution Transfer 2.5g of magnesium nitrate to a 500-mLvolumetric flask,and dissolve in and dilute with water to volume.
Test solution Transfer an accurately weighed quantity of about 0.1g of Glyceryl Distearate into a suitable high-pressure resistant digestion vessel (fluoropolymer or quartz),add 6.0mLof nitric acid and 2.0mLof 30%hydrogen peroxide.Place the closed vessel in a laboratory microwave oven,and digest using an appropriate program (e.g.,250Wfor 10minutes;600Wfor 5minutes;400Wfor 5minutes;and 250Wfor 7minutes.)Allow the digestion vessel to cool before opening.Quantitatively transfer the contents to a 25-mLvolumetric flask,dilute with water to volume,and mix.
Blank solution Add 6.0mLof nitric acid and 2.0mLof 30%hydrogen peroxide to a high-pressure resistant digestion vessel and proceed as directed for the Test solution.
Calibration solutions Transfer 5.0mLof nickel standard solution TSto a 10-mLvolumetric flask,add 0.5mLof nitric acid,1.0mLof 30percent hydrogen peroxide,and dilute with water to volume (stock solution).Into four identical 25-mLvolumetric flasks,each containing 6mLof nitric acid,transfer respectively 20,50,100,and 150µLof the stock solution obtained above,and dilute with water to volume.These solutions contain 4ng per mL,10ng per mL,20ng per nL,and 30ng per mLof nickel,respectively.
Zero solution Transfer 6.0mLof nitric acid to a 25-mLvolumetric flask,add a small amount of water,mix,and then dilute with water to volume.
Procedure Into seven separate 25-mLflasks,each containing 5.0mLof Magnesium nitrate solution,transfer respectively 10.0mLof each of the following:the Test solution,the Blank solution,the four Calibration solutions,and the Zero solution.Concomitantly determine the absorbances of these solutions at least three times each,at the wavelength of maximum absorbance at 232.0nm,with a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light-Scattering á851ñ)equipped with a pyrolytically-coated tube with a platform,graphite furnace,and a nickel hollow-cathode lamp.Maintain the drying temperature of the furnace at 100for 10seconds after a 10-second ramp,the ashing temperature at 1400for 10seconds after a 20-second ramp,and the atomization temperature at 2500for 5seconds.Use the Zero solutionto set the instrument to zero.Record the average of the steady readings for each of the solutions.[NOTEIf necessary,dilute the Test solutionwith theZero solutionto obtain a reading within the calibrated absorbance range]:not more than 1µg per g is found.
Limit of free glycerin
Mobile phase and Chromatographic system Proceed as directed in the Assay.
Standard solutions Prepare four solutions by dissolving accurately weighed quantities of glycerin in tetrahydrofuran,and diluting each with tetrahydrofuran,as necessary,to obtain solutions having known concentrations of about 0.2,0.4,1.0,and 2.0mg per mL.
Test solution Use the Assay preparation,prepared as directed in the Assay.
Procedure Separately inject equal volumes (about 40µL)of the Standard solutionsand the Test solutioninto the chromatograph,record the chromatograms,and measure the responses for the glycerin peaks.Plot the glycerin peak responses obtained versus the concentration,in mg per mL,of glycerin in the Standard solutions.From the standard curve so obtained,determine the glycerin concentration,C,in mg per mL,in the Test solution.Calculate the percentage of free glycerin in the portion of Glyceryl Distearate taken by the formula:
500(C/W),in which Cis as obtained above;and Wis the amount,in mg,of Glyceryl Distearate taken to prepare the Test solution:not more than 1.0%of free glycerin is found.
Mobile phase: tetrahydrofuran.
Assay preparation Transfer about 200mg of Glyceryl Distearate,accurately weighed,to a 5-mLvolumetric flask,dissolve in and dilute with tetrahydrofuran to volume,and mix.
Chromatographic system (see Chromatography á621ñ) The liquid chromatograph is equipped with a refractive index detector and a 7.5-mm ×60-cm column containing 5-µm 100Åpacking L21.The column and the detector temperatures are maintained at 40.[NOTETwo or three 7.5-mm ×30-cm L21columns may be used in place of the one 60-cm column provided that system suitability requirements are met;and the column temperature may be lowered to ambient temperature,although working at 40provides stable separation conditions and ensures better sample solubility.]The flow rate is about 1mLper minute.Chromatograph the Assay preparation,and record the peak responses as directed for Procedure:the relative retention times are about 1.0for glycerin,0.84for monoglycerides,0.78for diglycerides,and 0.75for triglycerides;the resolution,R,between the diglycerides and monoglycerides is not less than 1.0;and the relative standard deviation for replicate injections determined from the monoglycerides peak is not more than 2.0%.
Procedure Inject a volume (about 40µL)of the Assay preparation into the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the percentage of monoglycerides,diglycerides,and triglycerides in the portion of Glyceryl Distearate taken by the formula:
100(ri/rs),in which riis the individual peak response for the monoglycerides,diglycerides,and triglycerides,as appropriate;and rsis the sum of the responses for all of the glyceride peaks.
Auxiliary Information Staff Liaison:Elena Gonikberg,Ph.D.,Scientist
Expert Committee:(EMC)Excipients:Monograph Content
USP28NF23Page 3012Pharmacopeial Forum:Volume No.30(3)Page 975