Microcrystalline Cellulose
Cellulose.
Cellulose [9004-34-6].
»Microcrystalline Cellulose is purified,partially depolymerized cellulose prepared by treating alpha cellulose,obtained as a pulp from fibrous plant material,with mineral acids.
Packaging and storage—
Preserve in tight containers.
Labeling—
The labeling indicates the nominal loss on drying,bulk density,and degree of polymerization values.Degree of polymerization compliance is determined using Identificationtest B.Where the particle size distribution is stated in the labeling,the labeling indicates the d10,d50,and d90values and the range for each.
Identification—
A:
Prepare iodinated zinc chloride solution by dissolving 20g of zinc chloride and 6.5g of potassium iodide in 10.5mLof water.Add 0.5g of iodine,and shake for 15minutes.Place about 10mg of Microcrystalline Cellulose on a watch glass,and disperse in 2mLof iodinated zinc chloride solution:the substance takes on a violet-blue color.
B:
Transfer 1.3g of Microcrystalline Cellulose,accurately weighed to 0.1mg,to a 125-mLconical flask.Add 25.0mLof water and 25.0mLof 1.0Mcupriethylenediamine 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 7.0mLof the solution to a calibrated number 150Cannon-Fenske or equivalent1viscosimeter.Allow the solution to equilibrate at 25±0.1
for not less than 5minutes.Time the flow between the 2marks on the viscosimeter,and record the flow time,t1,in seconds.Calculate the kinematic viscosity,(KV)1,of the Microcrystalline Cellulose taken by the formula:
for not less than 5minutes.Time the flow between the 2marks on the viscosimeter,and record the flow time,t1,in seconds.Calculate the kinematic viscosity,(KV)1,of the Microcrystalline Cellulose taken by the formula:
t1(k1),
in which k1is the viscosimeter constant (see Viscosity á911ñ).Obtain the flow time,t2,for a 0.5Mcupriethylenediamine hydroxide solution using a number 100Cannon-Fenske or equivalent1viscosimeter.Calculate the kinematic viscosity,(KV)2,of the solvent by the formula:
t2(k2),
in which k2is the viscosimeter constant.Determine the relative viscosity,hrel,of the Microcrystalline Cellulose specimen taken by the formula:
(KV)1/(KV)2.
Determine the intrinsic viscosity,[h]c,by interpolation,using the Intrinsic Viscosity Tablein the Reference Tablessection.Calculate the degree of polymerization,P,by the formula:
((95)[h]c)/(WS[(100-%LOD)/100]),
in which WSis the weight,in g,of the Microcrystalline Cellulose taken;and %LODis the value obtained from the test for Loss on drying.The degree of polymerization is not greater than 350,and is within the labeled specification.
Microbial limits á61ñ—
The total aerobic microbial count does not exceed 1000cfu per g,the total combined molds and yeasts count does not exceed 100cfu per g,and it meets the requirements of the tests for absence of Staphylococcus aureusand Pseudomonas aeruginosaand for absence of Escherichia coliand Salmonellaspecies.
Conductivity—
Shake about 5g with 40mLof water for 20minutes,and centrifuge.Retain the supernatant for use in the pHtest.Using an appropriate conductivity meter that has been standardized with a potassium chloride conductivity calibration standard2having a conductivity of 100µSper 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 75µSper cm.
pHá791ñ:
between 5.0and 7.0in the supernatant obtained in the Conductivitytest.
Loss on drying á731ñ—
Dry it at 105for 3hours:it loses not more than 7.0%of its weight,or some other lower percentage,or is within a percentage range,as specified in the labeling.
for 3hours:it loses not more than 7.0%of its weight,or some other lower percentage,or is within a percentage range,as specified in the labeling.
Residue on ignition á281ñ:
not more than 0.05%.
Bulk density—
Use a volume meter3that has been fitted with a 10-mesh screen.The volume meter is freestanding of the brass or stainless steel cup,which is calibrated to a capacity of 25.0±0.05mLand has an inside diameter of 30.0±2.0mm.Weigh the empty cup,position it under the chute,and slowly pour the powder from a height of 5.1cm (2inches)above the funnel through the volume meter,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.
Water-soluble substances—
Shake 5.0g with about 80mLof water for 10minutes,filter with the aid of vacuum through filter paper (Whatman No.42or equivalent)into a vacuum flask.Transfer the filtrate to a tared beaker,evaporate to dryness without charring,dry at 105for 1hour,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 12.0mg (0.24%).
for 1hour,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 12.0mg (0.24%).
Ether-soluble substances—
Place 10.0g in a chromatography column having an internal diameter of about 20mm,and pass 50mLof 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 105for 30minutes,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 5.0mg (0.05%).
for 30minutes,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 5.0mg (0.05%).
Heavy metals,Method IIá231ñ:
0.001%.
Organic volatile impurities,Method IVá467ñ:
meets the requirements.
1
A Ubbelohde 1Cviscosimeter is equivalent to a Cannon-Fenske 150viscosimeter.A Ubbelohde 1viscosimeter is equivalent to a Cannon-Fenske 100viscosimeter.
2
Commercially available conductivity calibration solutions for conductivity meter standardization,standardized by methods traceable to the National Institute of Science and Technology (NIST),may be used.Solutions prepared according to instructions given in ASTM Standard D1125may be used provided the conductivity of the resultant solution is the same as that of the solution prepared from the NIST-certified material.
3
Asuitable apparatus is described as the Scott Volumeter in ASTM B329,available from the American Society for Testing and Materials,100Barr Harbor Drive,West Conshohocken,PA19429-2959.
Auxiliary Information—
Staff Liaison:Justin Lane,B.S.,Scientific Associate
Expert Committee:(EMC)Excipients:Monograph Content
USP28–NF23Page 2982
Pharmacopeial Forum:Volume No.30(4)Page 1433
Phone Number:1-301-816-8323