Hypromellose
Cellulose,2-hydroxypropyl methyl ether.
Cellulose hydroxypropyl methyl ether [9004-65-3].
»Hypromellose is a propylene glycol ether of methylcellulose.When dried at 105
for 2hours,it contains methoxy (–OCH3)and hydroxypropoxy (–OCH2CHOHCH3)groups conforming to the limits for the types of Hypromellose (hydroxypropyl methylcellulose)set forth in the accompanying table.
for 2hours,it contains methoxy (–OCH3)and hydroxypropoxy (–OCH2CHOHCH3)groups conforming to the limits for the types of Hypromellose (hydroxypropyl methylcellulose)set forth in the accompanying table.| Methoxy (percent) |
Hydroxypropoxy (percent) | |||
| Substitution Type | Min. | Max. | Min. | Max. |
| 1828 | 16.5 | 20.0 | 23.0 | 32.0 |
| 2208 | 19.0 | 24.0 | 4.0 | 12.0 |
| 2906 | 27.0 | 30.0 | 4.0 | 7.5 |
| 2910 | 28.0 | 30.0 | 7.0 | 12.0 |
Packaging and storage—
Preserve in well-closed containers.
Labeling—
Label it to indicate its substitution type and its viscosity type [viscosity of a solution (1in 50)].
Identification—
A:
Gently add 1g of Hypromellose to the top of 100mLof water in a beaker,and allow to disperse over the surface,tapping the top of the container to ensure an even dispersion of the substance.Allow the beaker to stand until the substance becomes transparent and mucilaginous (about 5hours),and then swirl the beaker to wet the remaining substance.Add a stirring bar,and stir until solution is complete:the mixture remains stable when an equal volume of 1Nsodium hydroxide or 1Nhydrochloric acid is added.
B:
Add 1g of Hypromellose to 100mLof boiling water,and stir the mixture:a slurry is formed,but the powdered material does not dissolve.Cool the slurry to 20,and stir:the resulting liquid is a clear or opalescent mucilaginous colloidal mixture.
,and stir:the resulting liquid is a clear or opalescent mucilaginous colloidal mixture.
C:
Pour a few mLof the mixture prepared for Identificationtest Bonto a glass plate,and allow the water to evaporate:a thin,self-sustaining film results.
Viscosity—
Place a quantity,accurately weighed and equivalent to 2g of solids on the dried basis,in a tared,wide-mouth,250-mLcentrifuge bottle,and add 98g of water previously heated to 80to 90.Stir with a propeller-type stirrer for 10minutes,place the bottle in an ice bath,continue the stirring,and allow to remain in the ice bath for 40minutes to ensure that hydration and solution are complete.Adjust the weight of the solution to 100g,if necessary,and centrifuge the solution to expel any entrapped air.Adjust the temperature of the solution to 20±0.1,and determine the viscosity in a suitable viscosimeter of the Ubbelohde type as directed for Procedure for Cellulose Derivativesunder Viscosity á911ñ.Its apparent viscosity is not less than 80.0%and not more than 120.0%of that stated on the label for viscosity types of 100centipoises or less,and not less than 75.0%and not more than 140.0%of that stated on the label for viscosity types higher than 100centipoises.
to 90.Stir with a propeller-type stirrer for 10minutes,place the bottle in an ice bath,continue the stirring,and allow to remain in the ice bath for 40minutes to ensure that hydration and solution are complete.Adjust the weight of the solution to 100g,if necessary,and centrifuge the solution to expel any entrapped air.Adjust the temperature of the solution to 20±0.1,and determine the viscosity in a suitable viscosimeter of the Ubbelohde type as directed for Procedure for Cellulose Derivativesunder Viscosity á911ñ.Its apparent viscosity is not less than 80.0%and not more than 120.0%of that stated on the label for viscosity types of 100centipoises or less,and not less than 75.0%and not more than 140.0%of that stated on the label for viscosity types higher than 100centipoises.
Loss on drying á731ñ—
Dry it at 105for 2hours:it loses not more than 5.0%of its weight.
for 2hours:it loses not more than 5.0%of its weight.
Residue on ignition á281ñ:
not more than 1.5%for Hypromellose having a labeled viscosity of greater than 50centipoises,not more than 3%for Hypromellose having a labeled viscosity of 50centipoises or less,and not more than 5%for Hypromellose 1828of all labeled viscosities.
Heavy metals,Method IIá231ñ:
0.001%,1mLof hydroxylamine hydrochloride solution (1in 5)being added to the solution of the residue.
Organic volatile impurities,Method IVá467ñ:
meets the requirements.
Assay—
[Caution—Hydriodic acid and its reaction byproducts are highly toxic.Perform all steps of the Assay preparation and the Standard preparation in a properly functioning hood.Specific safety practices to be followed are to be identified to the analyst performing this test.
]
Hydriodic acid—
Use a reagent having a specific gravity of at least 1.69,equivalent to 55%HI.
Internal standard solution—
Transfer about 2.5g of toluene,accurately weighed,to a 100-mLvolumetric flask containing 10mLof o-xylene,dilute with o-xylene to volume,and mix.
Standard preparation—
Into a suitable serum vial weigh about 135mg of adipic acid and 4.0mLof Hydriodic acid,pipet 4mLof Internal standard solutioninto the vial,and close the vial securely with a suitable septum stopper.Weigh the vial and contents accurately,add 30µLof isopropyl iodide through the septum with a syringe,again weigh,and calculate the weight of isopropyl iodide added,by difference.Add 90µLof methyl iodide similarly,again weigh,and calculate the weight of methyl iodide added,by difference.Shake,and allow the layers to separate.
Assay preparation—
Transfer about 0.065g of dried Hypromellose,accurately weighed,to a 5-mLthick-walled reaction vial equipped with a pressure-tight septum-type closure,add an amount of adipic acid equal to the weight of the test specimen,and pipet 2mLof Internal standard into the vial.Cautiously pipet 2mLof Hydriodic acidinto the mixture,immediately cap the vial tightly,and weigh accurately.Mix the contents of the vial continuously,while heating at 150for 60minutes.Allow the vial to cool for about 45minutes,and again weigh.If the weight loss is greater than 10mg,discard the mixture,and prepare another Assay preparation.
for 60minutes.Allow the vial to cool for about 45minutes,and again weigh.If the weight loss is greater than 10mg,discard the mixture,and prepare another Assay preparation.
Chromatographic system
(see Chromatography á621ñ)—The gas chromatograph is equipped with a thermal conductivity detector and a 4-mm ×1.8-m glass column packed with 20%liquid phase G28on 100-to 120-mesh support S1Cthat is not silanized.Helium is used as the carrier gas and the temperature of the column is maintained at 130.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative retention times are about 1.0,2.2,3.6,and 8.0for methyl iodide,isopropyl iodide,toluene,and o-xylene,respectively;and the resolution,R,between toluene and isopropyl iodide is not less than 2.0.
.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative retention times are about 1.0,2.2,3.6,and 8.0for methyl iodide,isopropyl iodide,toluene,and o-xylene,respectively;and the resolution,R,between toluene and isopropyl iodide is not less than 2.0.
Calibration—
Inject about 2µLof the upper layer of the Standard preparationinto the gas chromatograph,and record the chromatogram.Calculate the relative response factor,FM,of equal weights of toluene and methyl iodide taken by the formula:
QM/RSM,
in which QMis the quantity ratio of methyl iodide to toluene in the Standard preparation,and RSMis the peak area ratio of methyl iodide to toluene obtained from the Standard preparation.Similarly,calculate the relative response factor,FI,of equal weights of toluene and isopropyl iodide taken by the formula:
QI/RSI,
in which QIis the quantity ratio of isopropyl iodide to toluene in the Standard preparation,and RSIis the peak area ratio of isopropyl iodide to toluene obtained from the Standard preparation.
Procedure—
Inject about 2µLof the upper layer of the Assay preparationinto the gas chromatograph,and record the chromatogram.Calculate the percentage of methoxy (–OCH3)in the Hypromellose taken by the formula:
2(31/142)FMRUM(WT/WU),
in which 31/142is the ratio of the formula weights of methoxy and methyl iodide;FMis defined under Calibration;RUMis the ratio of the area of the methyl iodide peak to that of the toluene peak obtained from the Assay preparation;WTis the weight,in g,of toluene in the Internal standard solution;and WUis the weight,in g,of Hypromellose taken for the Assay.Similarly,calculate the percentage of hydroxypropoxy (–OCH2CHOHCH3)in the Hypromellose taken by the formula:
2(75/170)FIRUI(WT/WU),
in which 75/170is the ratio of the formula weights of hydroxypropoxy and isopropyl iodide;FIis defined under Calibration;RUIis the ratio of the area of the isopropyl iodide peak to that of the toluene peak obtained from the Assay preparation;WTis the weight,in g,of toluene in the Internal standard solution;and WUis the weight,in g,of Hypromellose taken for the Assay.
Auxiliary Information—
Staff Liaison:Justin Lane,B.S.,Scientific Associate
Expert Committee:(EMC)Excipients:Monograph Content
USP28–NF23Page 989
Phone Number:1-301-816-8323