Microcrystalline cellulose (MCC) HiCelTM is native from cellulose, which is manufactured from wood pulp. Microcrystalline cellulose is made by hydrolysis reaction at temperature and pressure in presence of catalyst, which acts as reaction process increment. It is neutralized after completion of hydrolysis and intended to be used as to make microcrystalline cellulose powder. HiCelTM MCC is white crystalline, free flowing powder and medium in particles size. MCC is free flowing with having physical & chemical properties as per limit and widely used as a pharmaceuticals aid for direct compression & wet granulation. MCC is employed for the production of solid dosage form due to its good compressibility, compatibility, and loading capacity of drugs. HiCelTM is very essential for direct compression because of its all parameter support to direct compression.
Keywords: Hydrolysis of wood pulp; Study of different grades of HiCelTM; Physical and Chemical parameter of microcrystalline cellulose HiCelTM
Microcrystalline cellulose is native from cellulose [1]. In pharmaceuticals industries most commonly source of microcrystalline cellulose is fibrous wood pulp [2]. Pulp is hydrolyzed under heat and pressure. In hydrolysis cellulose polymers breaks in presence of water and acid. The cellulose polymers in pulp are reduced to small chain polymers or microcrystals. Beta and gamma cellulose, hemicelluloses and lignin are dissolved with acid and water, and separate out during of washing and filtration; pure alpha cellulose neutralized and makes slurry [3]. A large amount of ยฉ cellulose present in wood pulp [4]. In TM market MCC HiCel grades are used in bulk for solid dosage form, food products and cosmeticโs products. Now days it used in manufacturing of cosmetics products such as face powder, creams, lotions and shampoos etc. It is use as fat substitute, thickener and as binder in cosmetics products. MCC TM HiCel broadly use in food product as a stabilizer, anti-caking agent, fat substitute and emulsifier [5][6]. This slurry is dried with the help of spray dryer and makes powder of microcrystalline cellulose TM HiCel . Behalf of little change of spray drier
Medium particle size standard MCC grades, suit for direct Fine particle standard MCC grades, granulation and now days used for direct compression also. Very fine particle size grade, Coars particle size MCC compatibility & high binding capacity. Its providing good content uniformity at low weight variation.
It is less Coars particle size than HiCel flow ability Its providing good content uniformity at low weight variation. It is medium particle size with extra low moisture grade MCC, It is It is fine particle size with extra low moisture grade MCC. It is large particle size with extra low moisture gr used for good binding with water sensitivity activity, It is medium particle size with high density grade MCC. It is used for improve the weight It fine particle size with high density grade MCC. It is used for improve the weight setting made different grads of MCC look like TM TM TM HiCel 90M, HiCel 50M, HiCel XLM, and TM HiCel LP200, these grades are differ-cent behalf of only physical parameters and TM various grade of HiCel MCC mention are in the Table no. 1. Physical parameters are changed grade vise and chemical parameters are mostly same of all grades. There are TM many grades of MCC HiCel used in
TM 1 HiCel 90M TM
TM 3 HiCel 25M TM Equal to HiCel TM 4 HiCel 14 TM 5 HiCel 12 TM
excellent TM 7 HiCel XLM 90M TM 8 HiCel XLM 50M TM
TM 10 HiCel HD 90 M TM
The amorphous regions are more flat to hydrolysis so partial depolymerized by acid hydrolysis results in shorter and more different formulation for makes differentdifferent solid dosages form which is employed as binder, filler (diluents), lubricant and as a disintegrant [7]. MCC TM HiCel microcrystalline cellulose powder has low bulk density and broad particle size distribution [7].
TM
compressible activities.
especially suit for wet gives a pleasant mouth feel, masks better tastes &supports flavors.
12 and with low moisture content, it is used for sensitivity activity grade, outstanding flow ability, good it can be used with low concentration of fine activity.
TM 12 MCC grade, it is , good compatibility & high binding capacity.
used for Water sensitivity activity.
ade MCC. It is variation of solid dosage form in direct compression formulation.
variation of solid dosage form in direct compression formulation crystalline fragments [8]. Flow ability of powder play a very important role in drug manufacturing process, in tablet 571 manufacturing process flow ability involved in mixing and compaction, such as powder flow in hoppers is a crucial factor for direct compression excipients in drug manufacturing to achieve constant and weight uniformity of tablets. Flow ability is affected by the physical properties of powder such as particle size, shape, bulk density [9]. Larger particle size is free flowing and smaller particle size (less than 100 ฮผ) is generally cohesive and flat to flow ability problems [9][10]. Small amounts of TM MCC HiCel are able to efficiently bind other materials, especially poorly tabletable active pharmaceutical ingredients [11]. In wood pulp cellulose chains are packed in layers held together by a crosslinking polymer (lignin) and strong hydrogen bonds. Dissolving pulps contains cellulose, hemicelluloses and lignin are present, and in cellulose contains alpha cellulose range is 92 % to 98 %, beta and gamma present 1% [12].
[13][14].
Fibrous Wood pulp is cut in to paces and hydrolyzed with acid (v/v) at temperature and pressure. Then slurry is transfer for washing and filtration after neutralization this wet MCC is further made to slurry (W/v) and is spray dried to evaporate water Flow chart of process is mention in the figure no. 1. Thus final MCC is obtained in powder form which is sifted to remove course material to meet the specified particle size requirements. Microcrystalline cellulose is white free flowing crystalline powder; it is shown in figure no. 2.
Fibrous wood pulp Hydrolysis Washing/ Filtration Wet MCC formed Drying TM HiCel MCC Packing TM
TM
Determination of yield value [14] A Yield (%) = X 100 (1) B Whereas; A= weight of obtained microcrystalline cellulose (kg), B= weight of fibrous wood pulp (kg) 572
celloulose [15] TM 10 mg of HiCel placed on watch glass 3 to 4 drops iodinated zinc chloride solution(20 gram of zinc chloride and 6.5 gram of potassium iodide in 10.5 ml of water, add 05 gram of iodine and shake for 15 to 20 mints (till it dissolved properly). Violet-blue color is changed.
Scanning electron microscopy [16] Scanning electron microscopy analysis screening was done outside laboratory in (Mumbai).
Average Particle size analysis [17] Average particle size was analyzed by (Retch-Japanese instrument). Take cleaned mesh sieve with bottom pan and top cover. Check sieve shaker and set mesh sieve with sample being analyzed on sieve jet. Arrange the sieve mesh sequence from top mesh +60, mesh +200 and bottom. Set the amplitude at 1.5 to 2.5 mm, timer at 5 to 7 minutes and interval time at 15 to 20 sec. Weight 10 gm of MCC powder with the help of weight blance (Mettler Toledo,Model no. ML802/A01) and put into top of sieve. After 5-7 minutes take out the sieves and weight the retention separately. Brush the mesh slowly from bottom and collect the all particles retained in between the mesh and consider as retention. Calculate the retention in percentage for each mesh sieve as per the following formula:- ๐(๐ ) Retention % = X 100 (2) ๐(๐) Whereas; S(R) = Sample retention weight (gram), S(W)= Sample taken weight (gram).
Bulk density [17][18] Untapped Density: Untapped density was analyzed through graduated measuring cylinder. Take 20 gm of dry MCC powder pours into a graduated A grade 100 ml capacity cylinder slowly from the sidewall. Level the surface of sample in cylinder by slow movement and note down the occupied volume and calculate the untapped density of MCC by using following formula.
Weight of powder in gram Untapped density (BD) = (3) Occupied volume in mL Tapped Density: Tapped density was anlaysed by using (Electro lab instrument, Model No. ETD1020), measuring cylinder placed in tapped density machine and fixed 100 tapped. After 100 tapped measured the volume of measuring cylinder and calculate TM the tapped density/porosity of HiCel using following formula.
Weight of powder in gram Tapped density (TD) = (4) Occupied volume in mL Hausnerโs Ratio [17][18] The flow of powder was measured by โHausner rationโ. Tapped density is divided by true density/untapped density.
๐๐ท Hausnerโs Ratio (H.R) = (5) ๐๐ต Whereas; TD- Tapped density of powder, TB- Untapped density of powder.
Angle of Repose [17][18] Pour 30gm of dry MCC through pour on powder flow tester (#10 mesh size), powder comes on the S.S cylinder surface until a pile build on the top of S.S cylinder. Measure the total height (S.S cylinder & pile) by scales. Using following formula find the calculated value this value check natural tangents chart for angle of repose and report angle of repose.
2๐ Angle of Repose = (6) ๐ 573 Whereas; h = height of S.S cylinder, d = diameter of S.S cylinder.
Moisture content (M.C) [17][18] Heat the shallow bottle in hot air oven (Model no. PNX-14) at 105ยฐC for 30 minutes after that cool it in desiccators at room temperature. Tare weight the Shallow bottle and take about 1 gm of TM HiCel MCC in shallow bottle, set oven at ๐ด๐๐ก๐๐ ๐๐๐ฆ๐๐๐ ๐ค๐๐๐ ๐๐ก ๐๐ ๐ ๐๐๐๐๐๐ค ๐๐๐ก๐ก๐๐ โ๐ธ๐๐ ๐ก๐ฆ (M.C) = ๐๐๐๐๐๐ ๐ค๐๐๐ ๐๐ก ๐๐ ๐๐๐๐ pH and conductivity Analysis [17][18] Take 5 gm of MCC powder add 40 ml of water mix 20 minutes with the help of glass rod and 20 minutes centrifuge(Remi elektrotechnik, Model no.-Remi-R-8CBL). Retain the supernatant for use analysis the pH by using pH meter (TOSHCON, Model no.-12/H/5563).
Same procedure was followed for conductivity test. Take retain supernatant and check conductivity with conductivity meter (TOSHCON, Model no.-13J1354). Conductivity meter was standardized with a potassium chloride conductivity calibration standard solution.
Degree of polymerization (DOP) [18] Transfer 1.3 gram of MCC sample accurately weighted to 0.1 mg to a 125 ml conical flask. Add 25 ml of water and 25 ml of 1 M cupriethylen diamine hydroxide solution. Insert the stopper and shake on wrist action shaker until completely dissolved. Transfer an appropriate volume of the solution to a calibrate number 150 Cannon-Fenske or equivalent viscosity meter. Allow the solution to equilibrate at 25 ยฐC ยฑ0.1 ยฐC for not less than 5 minutes. Time the flow between the two marks on viscosity meter and record the flow time, t in seconds. Calculate the kinematic 1 105ยฐC and kept for 3 hours. After 3 hours take out the shallow bottle, allow to cool in desiccators at room temperature. When the shallow bottle is cool take weight again, Calculate moisture content by using the following formula. This procedure repeats three times and takes the average value.
๐ค๐๐๐ ๐๐ก ๐๐ ๐ ๐๐๐๐๐๐ค ๐๐ ๐ก๐ก๐๐ X 100 (7) viscosity (KV)1 of MCC taken by the formula: t (K ).
1 1 In which, k1 is the viscosity meter constant. (See viscosity 911 in USP). Obtain the flow time t2 for a 0.5 M cupriethylene diamine hydroxide solution using a number 100 Cannon-Fenske or equivalent viscosity meter. Calculate the kinematic viscosity (kv)2 of the solvent by the formula, t2 (k2). In which k is the viscosity, (ฦ of MCC 2 rel specimen taken by the formula: (KV)1 / (KV)2.
(KV )1 ศ = (8) ๐พ๐ 2 Determine the intrinsic viscosity, (ฦ) c by interpolation, using the intrinsic viscosity table in reference table section. Calculate the DOP, it is denoted by โP โ.
95 ฦ ๐ถ P = (9) 100 โ%๐ฟ๐๐ท ๐๐ { } 100 Whereas; WS= weight of MCC powder, %LOD= Loss on drying of MCC powder Residue on ignition [18] Take a crucible and clean properly and Ignite in muffal furnace (Proto-tech, Model no.-PNX-14) at 600 ยฑ 50 ยฐC for 30 minutes. Placed in dissector and allow cool at room temperature. Tare weight of 574 crucible (CE) and take sample (SW) 1 to 2 TM gram HiCel MCC. Again weight the crucible with powder (CP) and add 2 ml of sulfuric acid, Heat on hot plate (Samiksha, Model No.-SI--12) at 100ยฐC. When white fumes is completely stop than crucible placed in muffal. After 3 hours switch off Muffal furnace and allow cool in dissector at room temperature. If it was not ignite properly again add 2 ml of sulfuric acid and process repeat again. Took weight of crucible with ignite residue (CI). Residue on ignition was calculated by using formula.
S = C -C (10) W P E (F ) = C -C (11) W I E ๐น๐ ROI = X 100 (12) ๐๐ Whereas; CE = Weight of empty crucible, C = Weight of Crucible with powder (MCC), P S = Weight of sample (MCC), W C = Weight if ignite residue with crucible, I FW = Final weight of ignite residue, ROI = Residue on ignition Water-soluble substances (WSS) [18] Properly clean, the evaporating dish(ED), and heat in hot air oven for 30 minutes, allow cool it in desiccators at room temperature. Took tare weight (AE) of evaporating dish. Weighed accurately 5 gram sample MCC powder (AP) and added 80 ml of water, stirred with glass rod till 10 minutes then filter by using filter paper (Whatman no.42) with the help of vacuum pump in to a vacuum flask. Transferred the filtrate to a tarred evaporating dish (ED), evaporated on water bath (Samiksh, Model No.-EI-13) and dry at 105 0C for about 1 hour. Cool evaporating dish in desiccators at room temperature. When it was cool take weight of ED (Ad). Found out the WSS value by using below formula. Same procedure was repeated for blank value. In blank only water was used, there was no other solvent used. Blank value (Bv) was calculated by using formula.
S = A โ A (13) W P E AF = AD - AE (14) ๐ด๐นโ๐ต๐ WSS = X 100 (15) ๐๐ Whereas; AE = Weight of empty evaporating dish (ED), AP = Weight of evaporating dish with sample (MCC), S = Weight of Sample MCC, W A = after drying weight of evaporating dish, D AF = Final weight of residue, BV = Blank value.
Yield: The yield of dissolving wood pulp is 90 to 92 % w/w. yield of three different batches mention in table no.3. Dissolving wood pulp contain high proportion of alpha cellulose, alpha cellulose is shiny white color. Yield was totally depending on grades and types of wood pulp.
TM Morphology of HiCel microcrystalline cellulose powder was studied through Scanning electron microscopy. The particles sizes were analyzed in micrometer, photomicrograph shown in figure no.3. Microcrystalline cellulose fibers were observed to be uniform in size and spherical in shape.
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Average Particle size analysis: Average TM particle size of HiCel microcrystalline cellulose was differentiated with different grades, it was shown in Table no.2 and HiCelTM 90 M average particle size (%) of three different batches were mentioned in table no.3.
Untapped density: Bulk density of TM HiCel microcrystalline cellulose was found to be 0.29 to 0.30 g/cc.
1 Yield (%) 90
2 55 (%) 3 Untapped density (g/cc) 0.29 4 Tapped density (g/cc) 0.39 5 Hausner ratio 1.34 6 Angle of repose 39 7 Moisture content 3.98 8 pH 6.14 9 Conductivity 52 10 DOP 233 11 ROI (%) 0.056 12 WSS (%) 0.13 Hausnerโs Ratio: Hausner ratio was TM presented the flow of powder, HiCel microcrystalline cellulose flow and hausnerโs ratio was reported 1.33 to 1.34.
Angle of repose: Angle of repose was represented the flow of powder. The flow TM ability of HiCel microcrystalline cellulose was very good; it was free flowing crystalline cellulose, Angle of repose was found to be 38ยฐ to 39ยฐ.
Moisture content: Moisture content of microcrystalline cellulose was found to be 3.98 to 4.00 %. In direct compression formulation less moisture content of
TM
TM 1 HiCel 90M 100 ฮผm TM 2 HiCel 50M 50 ฮผm TM 3 HiCel LP200 170 ฮผm TM 4 HiCel XLM 90M 100 ฮผm TM 5 HiCel XLM 50M 50 ฮผm Tapped density: Tapped density of TM HiCel microcrystalline cellulose was found to be 0.39 to 0.40 g/cc.
TM
92 92 56 55 0.29 0.30 0.39 0.40 1.34 1.33 38 39 4.00 4.00 6.15 6.20 50 50 235 233 0.056 .059 0.13 0.14 tablets was achieved as good hardness and disintegration time.
TM pH: pH of HiCel microcrystalline cellulose was maintained between 6.14 to 6.20. It was acceptable in all industries such as formulation, food and cosmetics also.
TM Conductivity: The Conductivity of HiCel microcrystalline cellulose was found to be 50 to 52 ฮผs/cm.
Degree of polymerization: Degree of TM polymerization of HiCel MCC was found to be 233 to 235. It was totally depend on 576 hydrolysis time, grade and types of wood pulp.
Residue on ignition: Residue on ignition TM of HiCel microcrystalline cellulose was found to be 0.056 to 0.059 % which was found in the range of 0.04 to 0.06 %.
Water soluble substances: Water soluble TM substances of HiCel microcrystalline cellulose was found to be 0.13 to 0.14 % which was found under the limits of IP not more than 0.2% and in USP not more than 0.25%.
TM Microcrystalline cellulose HiCel was spray dried cellulose; white crystalline, free flowing powder with excellent flow. Dissolving pulp was having very high MCC yield 87% to 92 %. It was found to be compatible for solid direct compression due to good properties of binding, lubrication and itself superdisintigrant.
The authors wish to thank chairman, managing director and general manager of ยฎ Sigachi Industries pvt. Ltd. Dahej Sez unit, for providing support and cooperation.