Hydroxypropyl Cellulose
Cellulose,2-hydroxypropyl ether [9004-64-2].
»Hydroxypropyl Cellulose is a partially substituted poly(hydroxypropyl)ether of cellulose.It may contain not more than 0.60percent of silica or other suitable anticaking agents.When dried at 105
for 1hour,it contains not more than 80.5percent of hydroxypropoxy groups.
for 1hour,it contains not more than 80.5percent of hydroxypropoxy groups.
Packaging and storage—
Store in well-closed containers.
Labeling—
Label it to indicate the viscosity in an aqueous solution of stated concentration and temperature.The indicated viscosity may be in the form of a range encompassing 50%to 150%of the average value.
Identification—
A:
Add about 1g to 100mLof water,previously heated to 60,and stir:a slurry is formed that swells and disperses on cooling to form a colloidal solution.
,and stir:a slurry is formed that swells and disperses on cooling to form a colloidal solution.
B:
Heat 10mLof the solution prepared in Identificationtest Aon a water bath while stirring:at a temperature of 45the solution becomes cloudy,or a flocculant precipitate is formed,which disappears on cooling.
the solution becomes cloudy,or a flocculant precipitate is formed,which disappears on cooling.
C:
Place 1mLof the solution prepared in Identificationtest Aon a glass plate,and allow the water to evaporate:a thin,self-sustaining film is formed.
Viscosity á911ñ—
Determine the apparent viscosity at the concentration and temperature specified on the label with a suitable rotational viscosimeter (see Labeling).
pHá791ñ:
between 5.0and 8.0,in a solution (1in 100).
Loss on drying á731ñ—
Dry it at 105for 3hours:it loses not more than 5.0%of its weight.
for 3hours:it loses not more than 5.0%of its weight.
Residue on ignition á281ñ—
[Caution—Perform the mixing and heating of the mixtures containing hydrofluoric acid in a well-ventilated hood.
]Proceed as directed for Residue on Ignition á281ñ,using a platinum crucible if silica may be present.If more than 0.2%residue is found,and silica is present,moisten the residue with water,and add about 5mLof hydrofluoric acid,in small portions.Evaporate on steam bath to dryness,and cool.Add about 5mLof hydrofluoric acid and about 0.5mLof sulfuric acid,and evaporate to dryness.Slowly increase the temperature until all of the acids have been volatilized,and ignite at 1000±25.Cool in a desiccator,and weigh:the difference between the final weight and the weight of the initially ignited portion represents the weight of silica,and the final weight is not more than 0.2%of the weight of test specimen taken for the ignition.
.Cool in a desiccator,and weigh:the difference between the final weight and the weight of the initially ignited portion represents the weight of silica,and the final weight is not more than 0.2%of the weight of test specimen taken for the ignition.
Lead á251ñ:
0.001%.
Heavy metals,Method IIá231ñ:
20µg per g.
Organic volatile impurities,Method IVá467ñ:
meets the requirements.
Assay for hydroxypropoxy groups—
Apparatus—
The apparatus for hydroxypropoxy group determinations is shown diagrammatically in Fig.1.
The boiling or reaction flask,consisting of a 125-mLconical-bottom boiling flask modified to provide a thermocouple (or thermometer)well and an inlet with a 1.0-mm capillary tip for nitrogen and water (see Fig.2),is fitted with a distillation head that leads to a condenser.The reaction flask is immersed in an oil bath equipped with an electric heater capable of heating the bath at the desired rate and maintaining the temperature at 155.The distillate is collected in a flask.[NOTE—The tube from the condenser to the flask must be below the surface of the liquid in the flask to ensure the capture of all of the acetic acid formed.See Fig.1.]
;)
Fig.1.Apparatus for hydroxypropoxy determination.
.The distillate is collected in a flask.[NOTE—The tube from the condenser to the flask must be below the surface of the liquid in the flask to ensure the capture of all of the acetic acid formed.See Fig.1.]
;)
Fig.2.Boiling flask
Procedure—
Transfer about 65mg of Hydroxypropyl Cellulose,previously dried at 105for 1hour and accurately weighed,into the reaction flask.Add 5mLof water,and swirl gently for 5minutes.Add 10mLof chromium trioxide solution (30g in 70mL).Assemble the apparatus as shown in Figures 1and 2,and immerse the reaction flask in the oil bath slightly above the level of the chromium trioxide solution.Start the condenser cooling water,and pass nitrogen gas through the flask at a rate of about 70to 75mLper minute.Raise the temperature of the oil bath to 155during a 30-minute period,and maintain it at this temperature throughout the determination.[NOTE—Too rapid an initial rise in temperature results in high blank determinations.]Monitor the temperature of the reaction mixture in the reaction flask using a thermocouple or thermometer in a well,as shown in Figures 1and 2.When a reaction mixture temperature of 102±1is reached,add water through the water inlet until the reaction mixture temperature drops to 97±1.Continue this 97to 102temperature cycle until 100mLof distillate has been collected.Detach the condenser from the distillation head,and wash with water,collecting the washings in the flask containing the distillate.Titrate the solution with 0.02Nsodium hydroxide VSto a pHof 7.0±0.1,using an expanded-scale pHmeter equipped with glass and calomel electrodes.Record the volume,V,of the 0.02Nsodium hydroxide used,then add 500mg of sodium bicarbonate and 10mLof 2Nsulfuric acid.After evolution of carbon dioxide has ceased,add 1g of potassium iodide,insert the stopper in the flask,shake the mixture,and allow the solution to stand in the dark for 5minutes.Titrate the liberated iodine with 0.02Nsodium thiosulfate VSto the sharp disappearance of the yellow iodine color,adding a few drops of starch TSto confirm the endpoint.Record the volume,Y,required.This titration,YmL,multiplied by the empirical factor,K,appropriate to the particular apparatus and reagents in use (see calculation below),gives the acid equivalent not caused by acetic acid.The acetic acid equivalent is (V-KY)mLof 0.02Nsodium hydroxide.
for 1hour and accurately weighed,into the reaction flask.Add 5mLof water,and swirl gently for 5minutes.Add 10mLof chromium trioxide solution (30g in 70mL).Assemble the apparatus as shown in Figures 1and 2,and immerse the reaction flask in the oil bath slightly above the level of the chromium trioxide solution.Start the condenser cooling water,and pass nitrogen gas through the flask at a rate of about 70to 75mLper minute.Raise the temperature of the oil bath to 155during a 30-minute period,and maintain it at this temperature throughout the determination.[NOTE—Too rapid an initial rise in temperature results in high blank determinations.]Monitor the temperature of the reaction mixture in the reaction flask using a thermocouple or thermometer in a well,as shown in Figures 1and 2.When a reaction mixture temperature of 102±1is reached,add water through the water inlet until the reaction mixture temperature drops to 97±1.Continue this 97to 102temperature cycle until 100mLof distillate has been collected.Detach the condenser from the distillation head,and wash with water,collecting the washings in the flask containing the distillate.Titrate the solution with 0.02Nsodium hydroxide VSto a pHof 7.0±0.1,using an expanded-scale pHmeter equipped with glass and calomel electrodes.Record the volume,V,of the 0.02Nsodium hydroxide used,then add 500mg of sodium bicarbonate and 10mLof 2Nsulfuric acid.After evolution of carbon dioxide has ceased,add 1g of potassium iodide,insert the stopper in the flask,shake the mixture,and allow the solution to stand in the dark for 5minutes.Titrate the liberated iodine with 0.02Nsodium thiosulfate VSto the sharp disappearance of the yellow iodine color,adding a few drops of starch TSto confirm the endpoint.Record the volume,Y,required.This titration,YmL,multiplied by the empirical factor,K,appropriate to the particular apparatus and reagents in use (see calculation below),gives the acid equivalent not caused by acetic acid.The acetic acid equivalent is (V-KY)mLof 0.02Nsodium hydroxide.
Obtain the empirical factor,K,for the apparatus by performing a blank determination in which the Hydroxypropyl Cellulose is omitted.The acidity of the blank for a given apparatus and given reagents is in a fixed ratio to the oxidizing equivalent of the distillate in terms of sodium thiosulfate:
Kfactor =(VB×N1)/(YB×N2),
in which VBis the volume,in mL,of 0.02Nsodium hydroxide required in blank run;N1is the normality of the 0.02Nsodium hydroxide;YBis the volume,in mL,of 0.02Nsodium thiosulfate required in blank run;and N2is equal to the normality of the 0.02Nsodium thiosulfate.
Calculate the percentage of hydroxypropoxy groups (–OCH2CHOHCH3)by the formula:
100(VAN1-KYAN2)(0.079/W),
in which VAis the volume,in mL,of 0.02Nsodium hydroxide required for titration of the sample;N1is the normality of the 0.02Nsodium hydroxide;Kis the empirical factor;YAis the volume,in mL,of 0.02Nsodium thiosulfate required for titration of the sample;N2is the normality of the 0.02Nsodium thiosulfate;and Wis the quantity,in g,of sample used.Each mLof 0.02Nsodium hydroxide is equivalent to 1.502mg of hydroxypropoxy groups (–OCH2CHOHCH3).
The results obtained as a percentage of hydroxypropoxy content may be converted to terms of average molecular substitution of glucose units by means of the accompanying graph (see Fig.3).
;)
Fig.3.Graph for converting percentage of substitution,by weight,of hydroxypropoxy groups to molecular substitution per glucose unit.
Auxiliary Information—
Staff Liaison:Justin Lane,B.S.,Scientific Associate
Expert Committee:(EMC)Excipients:Monograph Content
USP28–NF23Page 3017
Pharmacopeial Forum:Volume No.30(1)Page 335
Phone Number:1-301-816-8323