Legend: + will adopt and implement; - will not stipulate.

Nonharmonized attributes: Packaging and storage.

Specific local attributes: Appearance of solution (EP), Description (JP), Limit of glyoxal (EP).

A: Gently add 1 g of Hypromellose to the top of 100 mL of 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 for 1 to 2 minutes; the powdered material aggregates on the surface.

B: Add 1 g of Hypromellose to 100 mL of boiling water, and stir the mixture using a magnetic stirrer with a bar that is 25 mm long: a slurry is formed, but the powdered material does not dissolve. Cool the slurry to 10, and stir using a magnetic stirrer: the resulting liquid is a clear or slightly turbid solution with thickness dependent on the viscosity grade.

C:

for hypromellose samples having a viscosity type of less than 600 mPa·s— Transfer an accurately weighed quantity of Hypromellose, equivalent to 4 g of solids, calculated on the dried basis, to a tared, wide-mouth centrifuge bottle. Add hot water to obtain a total weight of the sample and water of 200.0 g. Capping the bottle, stir by mechanical means at 400 ± 50 rpm for 10 to 20 minutes until the particles are thoroughly dispersed and wetted out. Scrape down the walls of the bottle with a spatula, if necessary, to ensure that there is no undissolved material on the sides of the bottle, and continue the stirring in a cooling water bath equilibrated at a temperature below 10 for another 20 to 40 minutes. Adjust the solution weight, if necessary, to 200.0 g using cold water. Centrifuge the solution to expel any entrapped air. If any foam is present, remove with a spatula. Determine the viscosity in a suitable viscosimeter of the Ubbelohde type as directed for Procedure for Cellulose Derivatives under Viscosity 911: the viscosity is not less than 80% and not more than 120% of that stated on the label.

for hypromellose samples having a viscosity type of 600 mPa·s or higher— Transfer an accurately weighed quantity of Hypromellose, equivalent to 10 g of solids, calculated on the dried basis, to a tared, wide-mouth centrifuge bottle, and add hot water to obtain a total weight of the sample and water of 500.0 g. Capping the bottle, stir by mechanical means at 400 ± 50 rpm for 10 to 20 minutes until the particles are thoroughly dispersed and wetted out. Scrape down the walls of the bottle with a spatula, if necessary, to ensure that there is no undissolved material on the sides of the bottle, and continue the stirring in a cooling water bath equilibrated at a temperature below 10 for another 20 to 40 minutes. Adjust the solution weight if necessary to 500.0 g using cold water. Centrifuge the solution, if necessary, to expel any entrapped air. If any foam is present, remove with a spatula. Equip a suitable single cylinder type rotational viscosimeter (Brookfield type LV Model, or equivalent), and determine the viscosity of this solution at 20 ± 0.1 under the following operating conditions specified in the table below.

(Official until July 1, 2008)

Apparatus— For the reaction vial, use a 5-mL pressure-tight serum vial, 50 mm in height, 20 mm in outside diameter, and 13 mm in inside diameter at the mouth. The vial is equipped with a pressure-tight septum having a polytetrafluoroethylene-faced butyl rubber and an air-tight seal using an aluminum crimp or any sealing system that provides a sufficient air-tightness. Use a heater having a heating module that has a square-shape aluminum block with holes 20 mm in diameter and 32 mm in depth, into which the reaction vial fits. The heating module is also equipped with a magnetic stirrer capable of mixing the contents of the vial, or use a reciprocal shaker that performs a reciprocating motion of approximately 100 times per minute.

Hydriodic acid— Use a reagent having a typical concentration of HI about 57%.

Internal standard solution— Transfer about 3 g of n-octane, accurately weighed, to a 100-mL volumetric flask containing 10 mL of o-xylene, dilute with o-xylene to volume, and mix.

Standard preparation— Into a suitable serum vial weigh between 60 and 100 mg of adipic acid and add 2.0 mL of Hydriodic acid and 2.0 mL of Internal standard solution into the vial. Close the vial securely with a suitable septum stopper. Weigh the vial and contents accurately, add between 15 µL to 22 µL of isopropyl iodide through the septum with a syringe, weigh again, and calculate the weight of isopropyl iodide added, by difference. Add 45 µL of methyl iodide similarly, weigh again, and calculate the weight of methyl iodide added, by difference. Shake the reaction vial well, and allow the layers to separate. Use the upper layer as the Standard preparation.

Assay preparation— Transfer about 0.065 g of dried Hypromellose, accurately weighed, to a 5-mL thick-walled reaction vial equipped with a pressure-tight septum-type closure, add between 60 and 100 mg of adipic acid, and pipet 2.0 mL of Internal standard solution into the vial. Cautiously pipet 2.0 mL of Hydriodic acid into the mixture, immediately cap the vial tightly, and weigh accurately. Using the magnetic stirrer equipped in the heating module, or using a reciprocal shaker, mix the contents of the vial continuously, heating and maintaining the temperature of the contents at 130 ± 2 for 60 minutes. If a reciprocal shaker or magnetic stirrer cannot be used, shake the vial well by hand at 5-minute intervals during the initial 30 minutes of the heating time. Allow the vial to cool, and weigh accurately. If the weight loss is greater than or equal to 0.50% of the contents or there is evidence of a leak, discard the mixture, and prepare another Assay preparation.

Chromatographic system (see Chromatography 621)—The gas chromatograph is equipped with a thermal conductivity detector or hydrogen flame-ionization detector and a 3- to 4-mm × 1.8- to 3-m glass column packed with 20% liquid phase G28 on 100- to 120-mesh support S1C that is not silanized. Helium is used as the carrier gas for use with the thermal conductivity detector; helium or nitrogen can be used for the hydrogen flame-ionization detector. The temperature of the column is maintained at 100. Chromatograph the Standard preparation, and adjust the flow rate so that the retention time of the internal standard is about 10 minutes. Use a column giving well resolved peaks of methyl iodide, isopropyl iodide, and the internal standard in this order.

Procedure— Separately inject about 1 to 2 µL of the upper layer of the Standard preparation and the Assay preparation into the gas chromatograph, and record the chromatograms. Calculate the following. which is the ratio of the peak areas of methyl iodide to n-octane in the Assay preparation; which is the ratio of the peak areas of isopropyl iodide to n-octane in the Assay preparation; which is the ratio of the peak areas of methyl iodide to n-octane in the Standard preparation; and which is the ratio of the peak areas of isopropyl iodide to n-octane in the Standard preparation. Calculate the percentage of methoxy (–OCH3) in the Hypromellose taken by the formula: in which WSa is the weight, in mg, of methyl iodide in the Standard preparation; and WU is the weight, in mg, of Hypromellose, calculated on the dried basis, taken for the Assay preparation. Similarly, calculate the percentage of hydroxypropoxy (–OC3H6OH) in the Hypromellose taken by the formula: in which WSb is the weight, in mg, of isopropyl iodide in the Standard preparation; and WU is the weight, in mg, of Hypromellose, calculated on the dried basis, taken for the Assay preparation.