» 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 21.0 percent and not more than 35.0 percent 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.
Identification, Infrared Absorption 197K Do not dry specimens.
Viscosity 911 Dissolve 10 g, previously dried at 105 for 1 hour, in 90 g 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 Derivatives under Viscosity 911), is not less than 80% and not more than 120% of that indicated by the label.
Water, Method I 921: not more than 5.0%.
Residue on ignition 281: not more than 0.20%.
Chloride 221 Dissolve 1.0 g in 40 mL of 0.2 N sodium hydroxide, add 1 drop of phenolphthalein TS, and add 2 N nitric acid dropwise, with stirring, until the red color is discharged. Add an additional 20 mL of 2 N nitric 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-mL portions of water, separating the washings by centrifuging. Dilute the combined liquids with water to 200 mL, mix, and filter. A 50-mL portion of the filtrate so obtained shows no more chloride than a control solution made by treating 0.50 mL of 0.01 N hydrochloric acid with 10 mL of 0.2 N sodium hydroxide, adding 7 mL of 2 N nitric acid, and diluting with water to 50 mL (0.07%).
Heavy metals, Method II 231: 0.001%.
Limit of free phthalic acid
Mobile phase Prepare a filtered and degassed mixture of 0.1 M cyanoacetic acid and acetonitrile (85:15). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solution Transfer about 12.5 mg of phthalic acid, accurately weighed, to a 250-mL volumetric flask, add about 125 mL of acetonitrile, and mix to dissolve. Add 25 mL of water, dilute with acetonitrile to volume, and mix.
Test solution Transfer about 200 mg of Hypromellose Phthalate, accurately weighed, to a 100-mL volumetric flask, add about 50 mL of acetonitrile, and sonicate to dissolve partially. Add 10 mL of 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 L1 with a high carbon load. The flow rate is about 2.0 mL per 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 10 µL) of the Standard solution and the Test solution into 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 C is the concentration, in µg per mL, of phthalic acid in the Standard solution; W is the weight, in mg, on the anhydrous basis, of Hypromellose Phthalate taken to prepare the Test solution; and rU and rS are the phthalic acid peak responses obtained from the Test solution and the Standard solution, respectively: not more than 1.0% is found.
Phthalyl content Transfer about 1 g, accurately weighed, to a conical flask, dissolve in 50 mL of a mixture of alcohol, acetone, and water (2:2:1), add phenolphthalein TS, and titrate with 0.1 N sodium 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 149.1 and 166.1 are the molecular weights of the phthalyl group and phthalic acid, respectively; V is the volume, in mL, of 0.1 N sodium hydroxide consumed after correction for the blank; W is the weight, in g, calculated on the anhydrous basis, of Hypromellose Phthalate taken; and P is the percentage of free phthalic acid found as directed in the test for Limit of free phthalic acid.
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USP32NF27 Page 1257Pharmacopeial Forum: Volume No. 30(3) Page 984