Silicified Microcrystalline Cellulose
» Silicified Microcrystalline Cellulose is composed of intimately associated microcrystalline cellulose and colloidal silicon dioxide particles, derived from aqueous coprocessing prior to drying the material during manufacture. The microcrystalline cellulose component is purified, partially depolymerized cellulose, prepared by treating alpha cellulose, obtained as a pulp from fibrous plant material, with mineral acids. The colloidal silicon dioxide is a submicroscopic fumed silica prepared by the vapor-phase hydrolysis of a silicon compound. The Residue on ignition result indicates the percentage of colloidal silicon dioxide; the remainder is microcrystalline cellulose.
Packaging and storage— Preserve in tight containers. No storage requirements specified.
Labeling— Label it to indicate the nominal Loss on drying, Bulk density, and Degree of polymerization values. Where the particle size distribution is stated in the labeling, proceed as directed under Particle size distribution. The labeling indicates the technique with which the particle size distribution was determined, if a technique other than analytical sieving was used. The labeling also indicates the d10, d50, and d90 values and the range for each.
USP Reference standards 11
USP Silicified Microcrystalline Cellulose RS
Identification—
B: Prepare iodinated zinc chloride solution by dissolving 20 g of zinc chloride and 6.5 g of potassium iodide in 10.5 mL of water. Add 0.5 g of iodine, and shake for 15 minutes. Place about 10 mg of Silicified Microcrystalline Cellulose on a watch glass, and disperse in 2 mL of iodinated zinc chloride solution: the substance takes on a violet-blue color.
C: Transfer about 5 mg of residue from the test for Residue on ignition to a platinum crucible, and mix with about 200 mg of anhydrous potassium carbonate. Ignite at a red heat over a burner for about 10 minutes, and cool. Dissolve the melt in 2 mL of freshly distilled water, warming if necessary, and slowly add 2 mL of ammonium molybdate TS to the solution: a deep yellow color is produced.
D: Silica dispersion uniformity test
Conditioned test substance— Pass Silicified Microcrystalline Cellulose through an 850-µm sieve, disperse it into a suitable scale blender1, and tumble/mix the test substance for a minimum of 20 minutes to condition the material in preparation.
Procedure— Assemble a sieve stack composed of the following nested sieves: 60-, 80-, 120-, 200-, 325-, and 400-US mesh, plus pan. Tare each sieve to the nearest 0.1 g. Accurately weigh 200.0 g of the Conditioned test substance, and transfer to the top sieve. Agitate the sieve stack on a suitable sieve shaker for 20 minutes. Separate and record the weight of each sieve, including the Conditioned test substance fraction. Determine the Conditioned test substance fraction mass by difference. Analyze a test substance from each sieve fraction following Residue on ignition 281. Obtain the Residue on ignition (ROI) value in percentage, Pi, for each sieve fraction, excluding any fraction weighing less than 0.5 g. Calculate the average percentage of ROI value, PA, for Pi (i = 1–6). Calculate the variance for the sieve fraction, excluding the pan and any fraction weighing less than 0.5 g, by the formula:
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The variance should not exceed 0.02.
Microbial enumeration tests 61 and Tests for specified microorganisms 62 The total aerobic microbial count does not exceed 1000 cfu per g, and the total combined molds and yeasts count does not exceed 100 cfu per g.
Conductivity— Shake about 5 g with 40 mL of water for 20 minutes, and centrifuge. Retain the supernatant for use in the pH test. Using an appropriate conductivity meter that has been standardized with a potassium chloride conductivity calibration standard having a conductivity of 100 µS per cm, measure the conductivity of the supernatant after a stable reading is obtained, and measure the conductivity of the water used to prepare the test specimen. The conductivity of the supernatant does not exceed the conductivity of the water by more than 75 µS per cm.
pH 791: between 5.0 and 7.5 in the supernatant obtained in the Conductivity test.
Loss on drying 731 Dry it at 105 for 3 hours: it loses not more than 7.0% of its weight, within a percentage range, as specified in the labeling.
Residue on ignition 281: between 1.8% and 2.2%.
Bulk density— Use a volumeter that has been fitted with a 10-mesh screen. The volumeter is freestanding of the brass or stainless steel cup, which is calibrated to a capacity of 25.0 ± 0.05 mL, and has an inside diameter of 30.0 ± 2.0 mm. Weigh the empty cup, position it under the chute, and slowly pour the powder from a height of 5.1 cm (2 inches) above the funnel through the volumeter, at a rate suitable to prevent clogging, until the cup overflows. [note—If excessive clogging of the screen occurs, remove the screen. ] Level the excess powder, and weigh the filled cup. Calculate the Bulk density by dividing the weight of the powder in the cup by the volume of the cup: the Bulk density is within the labeled specification.
Degree of polymerization— Transfer 1.3 g of Silicified Microcrystalline Cellulose, accurately weighed to 0.1 mg, to a 125-mL conical flask. Add 25.0 mL of water and 25.0 mL of 1.0 M cupriethylenediamine hydroxide solution. Immediately purge the solution with nitrogen, insert the stopper, and shake on a wrist action shaker or other suitable mechanical shaker until completely dissolved. Transfer an appropriate volume of the solution to a calibrated number 150 Cannon-Fenske, or equivalent, viscometer. Allow the solution to equilibrate at 25 ± 0.1 for not less than 5 minutes. Time the flow between the two marks on the viscometer, and record the flow time, t1, in seconds. Calculate the kinematic viscosity, v1, of the Silicified Microcrystalline Cellulose taken by the formula:
t1(k1)
in which k1 is the viscometer constant (see Viscosity 911). Obtain the flow time, t2, for a 0.5 M cupriethylenediamine hydroxide solution using a number 100 Cannon-Fenske, or equivalent, viscometer. Calculate the kinematic viscosity, v2, of the solvent by the formula:
t2(k2)
in which k2 is the viscometer constant. Determine the relative viscosity, rel, of the Silicified Microcrystalline Cellulose specimen taken by the formula:
v1 / v2
Determine the intrinsic viscosity, []c, by interpolation, using the Intrinsic Viscosity Table in the Reference Tables section. Calculate the degree of polymerization, P, by the formula:
(95)[]c / {WS [(100 ROI)/100][(l00 LOD)/100]}
in which WS is the weight, in g, of the Silicified Microcrystalline Cellulose taken; ROI is the value, in percentage, obtained from the test for Residue on ignition; and LOD is the value, in percentage, obtained from the test for Loss on drying. The degree of polymerization is not greater than 350.
Particle size distribution— Where the labeling states the particle size distribution, determine the particle size distribution as directed in a suitable validated procedure.
Water-soluble substances— Shake 5.0 g with about 80 mL of water for 10 minutes, and filter with the aid of vacuum through filter paper (Whatman No. 42 or equivalent) into a vacuum flask. Transfer the filtrate to a tared beaker, evaporate to dryness without charring, dry at 105 for 1 hour, cool in a desiccator, and weigh: the difference between the weight of the residue and the weight obtained from a blank determination does not exceed 12.5 mg (0.25%).
Ether-soluble substances— Place 10.0 g in a chromatographic column having an internal diameter of about 20 mm, and pass 50 mL of peroxide-free ether through the column. Evaporate the eluate to dryness in a previously dried and tared evaporating dish with the aid of a current of air in a fume hood. After all of the ether has evaporated, dry the residue at 105 for 30 minutes, cool in a desiccator, and weigh: the difference between the weight of the residue and the weight obtained from a blank determination does not exceed 5.0 mg (0.05%).
Heavy metals, Method II 231: not more than 0.001%.

1  Planetary mixer, Turbula T2F mixer, or V-blender.
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