Compendium of the most significant studies with reference to properties, intake, effects.

Thoorens G, Krier F, Leclercq B, Carlin B, Evrard B. Microcrystalline cellulose, a direct compression binder in a quality by design environment--a review. Int J Pharm. 2014 Oct 1;473(1-2):64-72. doi: 10.1016/j.ijpharm.2014.06.055.

Abstract. Microcrystalline cellulose (MCC) is one of the most important tableting excipients thanks to its outstanding dry binding properties, enabling the manufacture of tablets by direct compression (DC). DC remains the most economical technique to produce large batches of tablets, however its efficacy is directly impacted by the raw material attributes.

Santos JMD, Ignácio EO, Bis-Souza CV, Silva-Barretto ACD. Performance of reduced fat-reduced salt fermented sausage with added microcrystalline cellulose, resistant starch and oat fiber using the simplex design. Meat Sci. 2021 May;175:108433. doi: 10.1016/j.meatsci.2021.108433.

Abstract.  The aim of this study was to evaluate fermented sausages with simultaneous reduction of fat (25%) and salt (25% KCl; 75% NaCl) using up to 2% of three different dietary fiber: microcrystalline cellulose (MCC), resistant starch (RS) and oat fiber (OF). Technological and sensory evaluations used the simplex-centroid mixture design.

Butler DC, Presnell SE, Bruner E, Page T, Cuff R, Phillips A. Microcrystalline Cellulose and Crospovidone Identified in Placentas With Vaginal Misoprostol Use. Am J Forensic Med Pathol. 2020 Sep;41(3):176-181. doi: 10.1097/PAF.0000000000000557.

Abstract. Microcrystalline cellulose and/or crospovidone was identified in 0 (0%) of 88 cases with no vaginal administration or low-dose vaginal administration and 29 (66%) of 44 placentas with high-dose vaginal administration. When identified, microcrystalline cellulose and/or crospovidone is most commonly present on the maternal surfaces of the extraplacental membranes.

Żelaziński T. Properties of Biocomposites from Rapeseed Meal, Fruit Pomace and Microcrystalline Cellulose Made by Press Pressing: Mechanical and Physicochemical Characteristics. Materials (Basel). 2021 Feb 13;14(4):890. doi: 10.3390/ma14040890.

Abstract. This paper presents the results of research on biocomposites made of the mixture of post-extraction rapeseed meal, microcrystalline cellulose and various fruit pomace (chokeberry, blackcurrant, apple and raspberry pomace). The biocomposites were made in the process of mechanical thickening by means of a heated mould (die and stamp) which is located between two heating elements installed on a hydraulic press. 

Casanova F, Pereira CF, Ribeiro AB, Freixo R, Costa E, E Pintado M, Fernandes JC, Ramos ÓL. Novel Micro- and Nanocellulose-Based Delivery Systems for Liposoluble Compounds. Nanomaterials (Basel). 2021 Oct 1;11(10):2593. doi: 10.3390/nano11102593.

Abstract. In this context, this review describes the fast-growing field of micro- and nanocellulose based delivery systems with a focus on the release of liposoluble bioactive compounds. The state of research on this field is reviewed in this article, which also covers the chemistry, preparation, properties, and applications of micro- and nanocellulose based delivery systems.

Alekseeva OV, Shibaeva VD, Noskov AV, Ivanov VK, Agafonov AV. Enhancing the Thermal Stability of Ionogels: Synthesis and Properties of Triple Ionic Liquid/Halloysite/MCC Ionogels. Molecules. 2021 Oct 14;26(20):6198. doi: 10.3390/molecules26206198.

Abstract.  In this study, an ionic liquid (IL), 1-butyl-3-methylimidazolium acetate, was used to prepare ionogels with microcrystalline cellulose (MCC) and halloysite (Hal). SEM, XRD, TG, DSC, FTIR spectroscopy, conductometry and mechanical tests were used to study the morphology, structure, thermal behaviour and electrophysical and mechanical characteristics of synthesised ionogels.

Portier C, Vigh T, Di Pretoro G, Leys J, Klingeleers D, De Beer T, Vervaet C, Vanhoorne V. Continuous twin screw granulation: Impact of microcrystalline cellulose batch-to-batch variability during granulation and drying - A QbD approach. Int J Pharm X. 2021 Mar 19;3:100077. doi: 10.1016/j.ijpx.2021.100077.

Abstract. This study assessed the impact of microcrystalline cellulose (MCC) batch-to-batch variability and process settings in a continuous twin screw wet granulation and semi-continuous drying line.

Klinger J, Daniels R. Assessing a Mass-Based Method for the Preparation of Low-Dosed Paediatric Capsules with Baclofen and Spironolactone. Pharmacy (Basel). 2021 Mar 8;9(1):56. doi: 10.3390/pharmacy9010056.

Abstract. The hard capsules were prepared using three different bulking agents consisting of either mannitol, lactose-monohydrate and microcrystalline cellulose mixed with 0.5% colloidal silica.

Microcrystalline Cellulose  (MCC) is an important linear carbohydrate polymer that is biodegradable, biocompatible, renewable, and a low-density compound. 

The name describes the structure of the molecule:

• Cellulose. This is an organic compound with the formula (C6H10O5)n, a polysaccharide consisting of a linear chain of several hundred to many thousands of β(1→4) linked D-glucose units. Cellulose is an important structural component of the primary cell wall of green plants, many forms of algae and the oomycetes. Some species of bacteria secrete it to form biofilms.
• Microcrystalline. This term refers to the small, crystalline structure of the material. Microcrystalline materials have crystals that are only visible under a microscope.

The synthesis process takes place in different steps:

• Preparation of cellulose, a natural polymer found in the cell walls of plants. It can be extracted from wood or cotton pulp through a process involving the removal of non-cellulosic impurities, typically using a combination of mechanical and chemical treatments.
• Hydrolysis. Cellulose is hydrolysed, typically using a mineral acid such as hydrochloric acid (HCl). This process breaks down cellulose into smaller crystalline fragments, hence the name "microcrystalline".
• Separation and washing. The resulting mixture is filtered to separate the microcrystalline cellulose from the acid and washed to remove any residual acid.
• Drying. The washed microcrystalline cellulose is then dried to remove residual water.

It commonly occurs as white crystal powder.

What it is used for and where

Microcrystalline cellulose is a term used to designate refined wood pulp and is used as a texturizer, anti-caking agent, fat substitute, emulsifier, extender, and bulking agent in food production. The most common form is used in vitamin supplements or tablets. It’s used in plaque analysis for virus count as an alternative to carboxymethylcellulose.

Food

Ingredient included in the list of European food additives as E460(i), stabiliser, thickener

Cosmetics

Abrasive agent. It contains abrasive particles to remove stains or biofilm that accumulate on the stratum corneum or teeth. Baking soda, kieselguhr, silica and many others have abrasive properties. Peeling or exfoliating products used in dermatology or cosmetic applications contain abrasive agents in the form of synthetic microspheres, however these microspheres or abrasive particles are not biodegradable and create pollution in aquatic ecosystems.

Absorbent. Absorbs substances dispersed or dissolved in aqueous solutions, water/oil, oil/water.

Anticaking agent. This compound facilitates free flow and prevents aggregation or clumping of substances in a formulation by reducing the tendency of certain particles to stick together.

Bulking agent. It regulates the water content, dilutes other solids, can increase the volume of a product for better flow, acts as a buffer against organic acids, helps to keep the pH of the mixture within a certain level.

Emulsion stabilizer. Emulsions are thermodynamically unstable. Emulsion stabilisers improve the formation and stability of single and double emulsions. It should be noted that in the structure-function relationship, molar mass plays an important role.

Light stabilizer. It prevents light from degrading light-sensitive components and slows down degradation reactions that have already begun. The mechanism is, in a way, similar to antioxidants and the effectiveness depends on the.complexity of the formulation and the density of the product.

Opacifying agent. It is useful into formulations that may be translucent or transparent to make them opaque and less permeable to light.

Viscosity control agent. It controls and adapts viscosity to the required level for optimal chemical and physical stability of the product and dosage in gels, suspensions, emulsions, solutions. 

Medical

In the pharmaceutical industry, t is inserted into the coating of medicinal tablets with a thickening and stabilizing function.

Studies

• Natural cellulose fibers contain crystalline and amorphous domains. Microcrystalline cellulose (MCC) can besynthesized by different processes such as reactive extrusion, enzyme mediated, and acid hydrolysis in that way the amorphous regions are removed and the crystalline domains remain. The hydroxyl groups covering the cellulose surface and orderly arrangement of molecules in MCC allows the cellulose to react well with a variety of materials, including conducting polymers. There are numerous composites of cellulose and its derivatives with synthetic polymers and biopolymers that have been used frequently in different applications such as biomedical applications, sensors and actuators and nanocomposites with good tensile strength (1).
• Considering its widespread usage in various fields, such as food,  pharmaceutical,  medical,cosmetic and polymer composites industries, microcrystalline cellulose (MCC) is becoming impellent due to increasing demand of alternatives to non-renewable and scarce fossil materials. Although it still suffers from some drawbacks, MCC has recently gained more interest owing to its renewability, non-toxicity, economic value, biodegradability, high mechanical properties, high surface area and biocompatibility. New sources, new isolation processes, and new treatments are currently under development to satisfy the increasing demand of producing new types of MCC-based materials on an industrial scale. Therefore, this review assembles the current knowledge on the isolation of MCC from different sources using various procedures, its characterization, and its application in bio-composites. Challenges and future opportunities of MCC-based composites are discussed as well as obstacles remaining for their extensive uses (2).
• The present study sheds light on the physical and chemical characteristics of microcrystalline cellulose (MCC) isolated from oil palm fronds (OPF) pulps. It was found that the OPF MCC was identified as cellulose II polymorph, with higher crystallinity index than OPF α-cellulose (CrIOPFMCC: 71%>CrIOPFα-cellulose: 47%). This indicates that the acid hydrolysis allows the production of cellulose that is highly crystalline. BET surface area of OPF MCC was found to be higher than OPF α-cellulose (SBETOPFMCC: 5.64m2g-1>SBETOPFα-cellulose:Qa0 2.04m2g-1), which corroborates their potential as an adsorbent. In batch adsorption studies, it was observed that the experimental data fit well with Langmuir adsorption isotherm in comparison to Freundlich isotherm. The monolayer adsorption capacity (Qa0) of OPF MCC was found to be around 51.811mgg-1 and the experimental data fitted well to pseudo-second-order kinetic model (3).
• Recycling of waste cotton fabrics (WCFs) and converting them into high value-added products have not been developed. In this study, a novel and green process was developed for the preparation of microcrystalline cellulose (MCC) from WCFs by the catalytic hydrolysis of phosphotungstic acid (H3PW12O40, HPW). The effects of hydrolysis conditions such as HPW concentration, reaction temperature, reaction time, and solid/liquid ratio were investigated. The optimum process conditions were determined as follows: HPW concentration of 3.47 mmol/L, a solid/liquid ratio of 1:40, reaction temperature of 140 °C, and reaction time of 6 h. The yield of MCC prepared was as high as 83.4% and exhibited better performance than commercial MCC such as a higher crystallinity (85.2%), smaller particle size (20.37 μm), and narrower particle size distribution (72.75%, 8.68-31.1 μm). Furthermore, the HPW could be extracted and recycled easily with diethyl ether for five times and used to prepare MCC with a high yield and crystallinity index (4).
• This study reports an inexpensive active filler of surface-modified microcrystalline cellulose (MCC) particle for reinforcement of polymer material. A commercial MCC powder with particle size of about 50 μm was mixed with urea and was then irradiated under microwave for the modification. The obtained urea-modified MCC (u-MCC) was able to be dispersed in a chitosan solution without precipitation for over 48 h, which provided a time window for its processing. After the mixture slurry was cast onto glass substrate and then coagulated in a NaOH aqueous solution, a full natural polymer composite film has been prepared. The mechanical properties of the obtained composite films have been carefully measured and discussed. Our results indicate that the mechanical properties reach the highest when the urea-modified MCC is 7 wt% in the composite film: the tensile strength, the breaking elongation, the Young's modulus and the fracture energy are respectively about 2.0, 2.1, 2.4 and 6.0 times those of the pure chitosan film. The reinforcement of the composite material with the u-MCC particles was studied through scanning electron microscopy, Fourier transform infrared spectroscopy and X-ray diffraction analyses, and has been attributed to the strong interaction between the surface-modified MCC particles and the neighboring chitosan chains in the film matrix. Moreover, the water vapor permeability and the transparency of the composite films have been determined to evaluate the potential applications such as gas impervious material and packaging material (5).
• Bio-inspired functionalization of microcrystalline cellulose aerogel with high adsorption performance toward dyes (6).
• In contrast to the conventional methods of improving interface and performances of plant fibre composites through fibre surface modification, this paper reports a novel approach based on the dispersion of microcrystalline cellulose (MCC) in the composite's matrix (7).
• The study describes the development of a vaccine using microcrystalline cellulose (Avicel PH-101) as a delivery carrier of recombinant protein-based antigen against erysipelas (8).

Microcrystalline Cellulose studies

Typical optimal characteristics of Microcrystalline Cellulose as a commercial product

• Molecular Formula : C₆H₁₀O₅  (C₆H₁₀O₅)n  (C₆H₁₀O₅)n=(162.06)n
• Molecular Weight:  342.2965
• CAS : 9004-34-6 
• UNII OP1R32D61U
• EC Number: 232-674-9
• DSSTox Substance ID: DTXSID3050492
• MDL number  MFCD00081512
• PubChem Substance ID 
• InChI Key    InChI=1S/C12H22O11/c13-1-3-5(15)6(16)9(19)12(22-3)23-10-4(2-14)21-11(20)8(18)7(10)17/h3-20H,1-2H2/t3?,4?,5?,6?,7?,8?,9?,10-,11?,12+/m1/s1
• SMILES    C(C1C(C(C(C(O1)OC2C(OC(C(C2O)O)O)CO)O)O)O)O
• IUPAC   (6S)-2-(hydroxymethyl)-6-[(3S)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol
• ChEBI    156274

Synonyms: 

• Cellulose powder

References________________________________________________________________

(1) Abdi MM, Md Tahir P, Liyana R, Javahershenas R.  A Surfactant Directed Microcrystalline Cellulose/Polyaniline Composite with Enhanced Electrochemical Properties.  Molecules. 2018 Sep 26;23(10). pii: E2470. doi: 10.3390/molecules23102470.

(2) Trache D, Hussin MH, Hui Chuin CT, Sabar S, Fazita MR, Taiwo OF, Hassan TM, Haafiz MK Microcrystalline cellulose: Isolation, characterization and bio-composites application-A review.  Int J Biol Macromol. 2016 Sep

(3) Hussin MH, Pohan NA, Garba ZN, Kassim MJ, Rahim AA, Brosse N, Yemloul M, Fazita MR, Haafiz MK. Physicochemical of microcrystalline cellulose from oil palm fronds as potential methylene blue adsorbents. Int J Biol Macromol. 2016 Jun

(4) Hou W, Ling C, Shi S, Yan Z. Preparation and characterization of microcrystalline cellulose from waste cotton fabrics by using phosphotungstic acid. Int J Biol Macromol. 2018 Nov 13;123:363-368. doi: 10.1016/j.ijbiomac.2018.11.112

(5) Huang X, Xie F, Xiong X.  Surface-modified microcrystalline cellulose for reinforcement of chitosan film. Carbohydr Polym. 2018 Dec 1;201:367-373. doi: 10.1016/j.carbpol.2018.08.085.

(6) Wei X, Huang T, Nie J, Yang JH, Qi XD, Zhou ZW, Wang Y.  Bio-inspired functionalization of microcrystalline cellulose aerogel with high adsorption performance toward dyes.  Carbohydr Polym. 2018 Oct 15;198:546-555. doi: 10.1016/j.carbpol.2018.06.112. 

(7) Pichandi S, Rana S, Parveen S, Fangueiro R. A green approach of improving interface and performance of plant fibre composites using microcrystalline cellulose.  Carbohydr Polym. 2018 Oct 1;197:137-146. doi: 10.1016/j.carbpol.2018.05.074. Epub 2018 May 26.

(8) Jeon W, Kim YC, Hong M, Rejinold S, Park K, Yoon I, Yoo S, Lee H, Ahn J. Microcrystalline Cellulose for Delivery of Recombinant Protein-Based Antigen against Erysipelas in Mice. Biomed Res Int. 2018 Jun 11;2018:7670505. doi: 10.1155/2018/7670505. eCollection 2018.

(8) Jeon W, Kim YC, Hong M, Rejinold S, Park K, Yoon I, Yoo S, Lee H, Ahn J. Microcrystalline Cellulose for Delivery of Recombinant Protein-Based Antigen against Erysipelas in Mice.  Biomed Res Int. 2018 Jun 11;2018:7670505. doi: 10.1155/2018/7670505. eCollection 2018