11/7/2020 USP-NF Silicified Microcrystalline Cellulose

Printed on: Sat Nov 07 2020, 10:02:02 am

Printed by: Shruti Kharidia
O cial Status: Currently O cial on 07-Nov-2020
O cial Date: O cial as of 1-May-2020
Document Type: NF
DocId: 1_GUID-9A791BB6-EC13-4CAE-A3C4-81DFA0D76878_4_en-US
Printed from: https://online.uspnf.com/uspnf/document/1_GUID-9A791BB6-EC13-4CAE-A3C4-81DFA0D76878_4_en-US
© 2020 USPC

Silici ed Microcrystalline Cellulose

DEFINITION
Silici ed 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 puri ed, partially depolymerized cellulose, prepared by treating alpha cellulose, obtained as a pulp from brous 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.

IDENTIFICATION

Change to read:
• A. ▲SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉, Infrared Spectroscopy: 197K▲ (CN 1-MAY-2020)

• B.
Sample: 10 mg
Iodinated zinc chloride solution: Dissolve 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 min.
Analysis: Place the Sample on a watch glass, and disperse in 2 mL of Iodinated zinc chloride solution.
Acceptance criteria: The substance takes on a violet-blue color.
• C.
Sample: 5 mg of residue from the test for Residue on Ignition L
Analysis: Transfer the Sample to a platinum crucible, and mix with about 200 mg of anhydrous potassium carbonate. Ignite at a red
IA
heat over a burner for about 10 min, 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.
Acceptance criteria: A deep yellow color is produced.
• D. SILICA DISPERSION UNIFORMITY TEST
IC

Conditioned test substance: Pass Silici ed Microcrystalline Cellulose through an 850-µm sieve, disperse it into a suitable scale
blender,1 and tumble/mix the test substance for a minimum of 20 min to condition the material in preparation.
Analysis: 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. Weigh 200.0 g of the Conditioned test substance, and transfer to the top sieve. Agitate the sieve
FF

stack on a suitable sieve shaker for 20 min. 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,
using 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:
O

Result = Σ (Pi − PA)2/(n − 1)

i = 1

Acceptance criteria: NMT 0.02

SPECIFIC TESTS
• RESIDUE ON IGNITION 〈281〉: 1.8%–2.2%

• MICROBIAL ENUMERATION TESTS 〈61〉and TESTS FOR SPECIFIED MICROORGANISMS 〈62〉: The total aerobic microbial count does not exceed 103
cfu/g, and the total combined molds and yeasts count does not exceed 102 cfu/g.
• CONDUCTIVITY
Sample: 5 g
Analysis: Shake the Sample with 40 mL of water for 20 min, 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/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.
Acceptance criteria: The conductivity of the supernatant does not exceed the conductivity of the water by more than 75 µS/cm.
• PH 〈791〉: 5.0–7.5 for the supernatant obtained in the Conductivity test
• LOSS ON DRYING 〈731〉
Analysis: Dry at 105° for 3 h.
https://online.uspnf.com/uspnf/document/1_GUID-9A791BB6-EC13-4CAE-A3C4-81DFA0D76878_4_en-US?source=TOC 1/3
11/7/2020 USP-NF Silicified Microcrystalline Cellulose

Acceptance criteria: NMT 7.0%, within a percentage range, as speci ed in Labeling

• DEGREE OF POLYMERIZATION
Sample: 1.3 g, weighed to 0.1 mg
Analysis: Transfer the Sample to a 125-mL conical ask. 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 NLT 5 min. Time the ow between the two marks
on the viscometer.
Calculate the kinematic viscosity of the Sample taken:

ν1 = t1 × k1

t1 = time of ow between the two marks on the viscometer (s)

k1 = viscometer constant (see Viscosity—Capillary Methods 〈911〉)

Obtain the ow time for a 0.5 M cupriethylenediamine hydroxide solution, using a number 100 Cannon-Fenske, or equivalent,
viscometer.
Calculate the kinematic viscosity of the solvent:

ν2 = t2 × k2

t2 = time of ow for a 0.5 M cupriethylenediamine hydroxide solution (s)

k2 = viscometer constant

Determine the relative viscosity of the Silici ed Microcrystalline Cellulose taken:

Result = ν1/ν2
Calculate the degree of polymerization:
L
Result = 95 × [η]c/{WS × [(100 − ROI)/100] × [(100 − LOD)/100]}
IA
[η]c = value from interpolation of the relative viscosity, using the Intrinsic Viscosity Table in the Reference Tables section

WS = weight of the sample taken (g)

IC

ROI = value from the test for Residue on Ignition (%)

LOD = value from the test for Loss on Drying (%)

Acceptance criteria: NMT 350

FF

• BULK DENSITY
Sample: Silici ed Microcrystalline Cellulose powder
Analysis: Use a volumeter that has been tted 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 over ows. [NOTE—If excessive clogging of the screen occurs, remove the screen.] Level the
O

excess powder, and weigh the lled cup. Calculate the bulk density by dividing the weight of the powder in the cup by the volume of
the cup.
Acceptance criteria: Within the labeled speci cation
• 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
Sample: 5.0 g
Analysis: Shake the Sample with 80 mL of water for 10 min, and lter with the aid of vacuum through lter paper (Whatman No. 42 or
equivalent) into a vacuum ask. Transfer the ltrate to a tared beaker, evaporate to dryness without charring, dry at 105° for 1 h, cool
in a desiccator, and weigh.
Acceptance criteria: NMT 0.25%; the difference between the weight of the residue and the weight obtained from a blank
determination is NMT 12.5 mg.
• ETHER-SOLUBLE SUBSTANCES
Sample: 10.0 g
Analysis: Place the Sample 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 the ether has evaporated, dry the residue at 105° for 30 min, cool in a desiccator, and weigh.

https://online.uspnf.com/uspnf/document/1_GUID-9A791BB6-EC13-4CAE-A3C4-81DFA0D76878_4_en-US?source=TOC 2/3
11/7/2020 USP-NF Silicified Microcrystalline Cellulose

Acceptance criteria: NMT 0.05%; the difference between the weight of the residue and the weight obtained from a blank
determination is NMT 5.0 mg.

ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight containers. No storage requirements speci ed.
• 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 in 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 Silici ed Microcrystalline Cellulose RS

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

Auxiliary Information- Please check for your question in the FAQs before contacting USP.

Topic/Question Contact Expert Committee

SILICIFIED MICROCRYSTALLINE Sean P Delaney CE2020 Complex Excipients

CELLULOSE Assistant Scienti c Liaison

Chromatographic Database Information: Chromatographic Database

Most Recently Appeared In:

Pharmacopeial Forum: Volume No. 34(5)

L
IA
Page Information:

USP43-NF38 - 5699
USP42-NF37 - 5652
USP41-NF36 - 5279

Current DocID: GUID-9A791BB6-EC13-4CAE-A3C4-81DFA0D76878_4_en-US

IC
FF
O

https://online.uspnf.com/uspnf/document/1_GUID-9A791BB6-EC13-4CAE-A3C4-81DFA0D76878_4_en-US?source=TOC 3/3