Hypromellose Phthalate
»Hypromellose Phthalate is a monophthalic acid ester of hydroxypropyl methylcellulose.It contains methoxy (–OCH3),hydroxypropoxy (–OCH2CHOHCH3),and phthalyl (o-carboxybenzoyl,C8H5O3)groups.It contains not less than 21.0percent and not more than 35.0percent of phthalyl groups,calculated on the anhydrous basis.
Packaging and storage—
Preserve in tight containers.
Labeling—
Label it to indicate its viscosity and its nominal phthalyl content.
USP Reference standards á11ñ—
USP Hydroxypropyl Methylcellulose Phthalate RS.
Identification,Infrared Absorption á197Kñ—
Do not dry specimens.
Viscosity á911ñ—
Dissolve 10g,previously dried at 105
for 1hour,in 90g of a mixture of equal weights of methanol and methylene chloride by mixing and shaking:the viscosity,determined at 20±0.1,(see Procedure for Cellulose Derivativesunder Viscosity á911ñ)is not less than 80%and not more than 120%of that indicated by the label.
for 1hour,in 90g of a mixture of equal weights of methanol and methylene chloride by mixing and shaking:the viscosity,determined at 20±0.1,(see Procedure for Cellulose Derivativesunder Viscosity á911ñ)is not less than 80%and not more than 120%of that indicated by the label.
Water,Method Iá921ñ:
not more than 5.0%.
Residue on ignition á281ñ:
not more than 0.20%.
Chloride á221ñ—
Dissolve 1.0g in 40mLof 0.2Nsodium hydroxide,add 1drop of phenolphthalein TS,and add 2Nnitric acid dropwise,with stirring,until the red color is discharged.Add an additional 20mLof 2Nnitric acid with stirring.Heat on a water bath,with stirring,until the gel-like precipitate formed becomes granular.Cool the mixture,and centrifuge.Separate the liquid phase,and wash the residue with three successive 20-mLportions of water,separating the washings by centrifuging.Dilute the combined liquids with water to 200mL,mix,and filter.A50-mLportion of the filtrate so obtained shows no more chloride than a control solution made by treating 0.50mLof 0.01Nhydrochloric acid with 10mLof 0.2Nsodium hydroxide,adding 7mLof 2Nnitric acid,and diluting with water to 50mL(0.07%).
Heavy metals,Method IIá231ñ:
0.001%.
Limit of free phthalic acid—
Mobile phase—
Prepare a filtered and degassed mixture of 0.1Mcyanoacetic acid and acetonitrile (85:15).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard solution—
Transfer about 12.5mg of phthalic acid,accurately weighed,to a 250-mLvolumetric flask,add about 125mLof acetonitrile,and mix to dissolve.Add 25mLof water,dilute with acetonitrile to volume,and mix.
Test solution—
Transfer about 200mg of Hypromellose Phthalate,accurately weighed,to a 100-mLvolumetric flask,add about 50mLof acetonitrile,and sonicate to dissolve partially.Add 10mLof water,and sonicate to dissolve.Cool to room temperature,dilute with acetonitrile to volume,and mix.
Chromatographic system—
The liquid chromatograph is equipped with a 235-nm detector and a 4.6-mm ×25-cm column that contains packing L1with a high carbon load.The flow rate is about 2.0mLper minute.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 1.0%.
Procedure—
Separately inject equal volumes (about 10µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the peak responses.Calculate the percentage of phthalic acid in the portion of Hypromellose Phthalate taken by the formula:
10(C/W)(rU/rS),
in which Cis the concentration,in µg per mL,of phthalic acid in the Standard solution;Wis the weight,in mg,on the anhydrous basis,of Hypromellose Phthalate taken to prepare the Test solution;and rUand rSare the phthalic acid peak responses obtained from the Test solutionand the Standard solution,respectively:not more than 1.0%is found.
Organic volatile impurities,Method IVá467ñ:
meets the requirements.
Phthalyl content—
Transfer about 1g,accurately weighed,to a conical flask,dissolve in 50mLof a mixture of alcohol,acetone,and water (2:2:1),add phenolphthalein TS,and titrate with 0.1Nsodium hydroxide VS.Perform a blank determination,and make any necessary correction.Calculate the percentage of phthalyl taken by the formula:
0.01(149.1)(V/W)-2(149.1/166.1)(P),
in which 149.1and 166.1are the molecular weights of the phthalyl group and phthalic acid,respectively;Vis the volume,in mL,of 0.1Nsodium hydroxide consumed after correction for the blank;Wis the weight,in g,calculated on the anhydrous basis,of Hypromellose Phthalate taken;and Pis the percentage of free phthalic acid found as directed in the test for Limit of free phthalic acid.
Auxiliary Information—
Staff Liaison:Justin Lane,B.S.,Scientific Associate
Expert Committee:(EMC)Excipients:Monograph Content
USP28–NF23Page 3020
Pharmacopeial Forum:Volume No.30(3)Page 984
Phone Number:1-301-816-8323