Microcrystalline cellulose compression

It may sometimes by necessary to supplement the properties of the drug so that it compresses more easily, and these needs have been realized by several manufacturers of excipients. Materials described as compression aids are now commercially available. Ideally, such adjuvants should develop mechanical strength while improving, or at least not adversely affecting, release characteristics. Among the most successful at meeting both these needs have been the microcrystalline celluloses (partially acid-hydrolyzed forms of cellulose). A number of grades are available based upon particle size and distribution. 

A. Gupta, G.E. Peck, R.W. Miller and K.R. Morris, Influence of ambient moisture on the compaction behavior of microcrystalline cellulose powder undergoing uni-axial compression and roller compaction a comparative study using near-infrared spectroscopy, J. Pharm. Sci., 94(10), 2301-2313 (2005). 

Harrison et al. (27,31) obtained force-displacement profile during extrusion of microcrystalline cellulose (MCC) only formulations using a ram extruder and resolved it into three stages, as seen in Figure 9 compression, steady state, and forced flow. Based on surface smoothness and cohesive strength, a predominant steady state region was found necessary... 

Gohel MC, Jogani PD. An investigation of the direct-compression characteristics of coprocessed lactose-microcrystalline cellulose using statistical design. Pharm Technol 1999 54-62. 

Limwong Y, Sutanthavibul N, Kulvanich P. Spherical composite particles of rice starch and microcrystalline cellulose a new coprocessed excipient for direct compression. AAPS Pharm Sci Tech 2004 5 (article 30). 

Material flow and compressibility. A free flowing, highly compressible material such as microcrystalline cellulose may be used for drugs with poor flow or compressibility properties. 

There are many commercially available direct compression filler-binders. The most commonly used filler-binders include spray-dried lactose, mannitol, microcrystalline cellulose, pregelatinized starch, and dibasic calcium phosphate. Many factors affect the selection of a filler-binder for a direct compression tablet formulation. The most important requirements for a directly compressible filler-binder used in a low-dose formulation are listed below ... 

Microcrystalline Cellulose. Microcrystalline cellulose is a purified, partially depolymerized cellulose that occurs as a white, odorless, tasteless, crystalline powder composed of porous particles. It is widely used in pharmaceutical dosage forms, primarily as a filler-binder in oral tablets and capsules with both wet granulation and direct compression processes. Microcrystalline cellulose was marketed first in 1964 by the FMC Corporation under name Avicel PH in four different particle size grades, each with different properties.37 Addition of Avicel into a spray-dried lactose-based formulation overcame compressibility problems. At the same time, the lactose enhanced the flowability of the Avicel products available at that time. The direct compression tableting process became a reality, rather than a concept, partially because of the availability of Avicel. As of 2007, Avicel PH is commercially available in 10 types with different particle size, density, and moisture grades that have different properties and applications (Table 7.6).38 Other brands of microcrystalline cellulose are also available on the pharmaceutical market, including Pharmacel 101 and 102 from DMV International and Emcocel 50 M and 90 M from JRS Pharma. 

Microcrystalline cellulose is one of the most commonly used filler-binders in direct compression formulations because it provides good binding properties as a dry binder, excellent compactibility, and a high dilution potential. It also contributes good disintegration and lubrication characteristics to direct compression formulas. When compressed, microcrystalline cellulose undergoes plastic deformation. The acid hydrolysis portion of the production process introduces slip planes and dislocations into the material. Slip planes, dislocations, and the small size of the individual crystals aid in the plastic flow that takes place. The spray-dried particle itself, which has a higher porosity compared with the absolute porosity of cellulose, also deforms... 

Microcrystalline cellulose is the most compressible of any direct compression excipient. Producing a tablet of a given hardness requires less compression force for other materials. Therefore, it is usually mixed with another filler to achieve ideal compactibility and flowability of a direct compression formulation. Large particle size grades of microcrystalline cellulose are made by spray-dried processes to form dry and porous particle surfaces. The porous surfaces provide adsorption sites needed for fine dmg particles in low-dose formulations. However, microcrystalline cellulose contains trace amounts of peroxides that may lead to chemical incompatibility with oxidatively sensitive dmg substances.34... 

Microcrystalline cellulose (MCC) is obtained by a controlled acid treatment intended to destroy the molecular bonding in the amorphous zones of cellulose. Usually HC1 or H2SO4 are used at 110°C for 15 min over native cellulose or regenerated cellulose. Colloidal gels are thus obtained showing thixotropy. MCC is used in the preparation of pharmaceutical compressed tablets due to its binding and disintegration properties. 

Microcrystalline cellulose (Avicel) is purified partially depolymerized cellulose, prepared by treating a-cellulose with mineral acids. In addition to being used as a filler, it is also used as dry binder and disintegrant in tablet formulations. Depending on the preparation conditions, it can be produced with a variety of technical specifications depending on particle size and crystallinity. It is often used as an excipient in direct compression formulations but can also be incorporated as a diluent for tablets prepared by wet granulation, as a filler for capsules and for the production of spheres. 

Oralsolv (CIMA Labs Inc.) Remeron Soltab Mirtazepine (15, 30, or 45mg), aspartame, citric acid, crospovidone, hydroxypropyl methylcellulose, magnesium stearate, mannitol, microcrystalline cellulose, polymethacrylate, povidone, sodium bicarbonate, starch, sucrose, orange flavor Compression... 

Tablet diluent Inert substance used as filler to create desired bulk, flow properties, and compression characteristics in preparation of tablets Dibasic calcium phosphate, kaolin, lactose, mannitol, microcrystalline cellulose, powdered cellulose, precipitated calcim carbonate, sorbitol, starch...

Microcrystalline cellulose Strong wicking action loses disintegrant action when highly compressed... 

The third class of lubricant activity is the antiadherent. Some materials have adhesive properties and can adhere to the punch surfaces during compression. This will induce tablet disorders sticking, with a film forming on the surface of the tablets, or picking, where solid particles from the tablet stick to the punch surface. Most die wall lubricants also have antiadherent actions, and in many formulations, the addition of a specific antiadherent will not be required separately. The antiadherent includes talc, maize starch, and microcrystalline cellulose. 

Schmidt, P. C., and Leitritz, M. (1997), Compression force/time-profiles of microcrystalline cellulose, dicalcium phosphate dihydrate and their binary mixtures—A critical consideration of experiments and parameters, Eur. J. Pharm. Biopharm., 44, 303-313. 

Moisute acts as a plasticizer and influences the mechanical properties of powdered materials for tablet compression. In the case of microcrystalline cellulose, at moisture levels above 5% the material exhibits significant changes consistent with a transition from the glassy state to the rubbery state [17]. The possible influence of moisture on the compaction behavior of powders was also analyzed by Gupta et al. [18]. This work evaluates the effect of variation in the ambient moisture on the compaction behavior of microcrystalline cellulose powder. 

Different localized levels of molecular order can coexist in some pharmaceutical materials, giving rise to the occurrence of partially crystalline (and partially amorphous ) systems. In most cases, the properties of such materials (e.g., density) are intermediate to those of the 100% amorphous and 100% crystalline samples. By deliberately varying the level of crystallinity in such systems, their properties can be customized for a particular purpose. An example of this is with the tableting excipients microcrystalline cellulose and spray-dried lactose, which have had their compression characteristics optimized by manipulating their amorphous content. The properties of partially crystalline materials may be approximated in many instances by making physical mixtures of the totally amorphous and crystalline samples. This is known as the two-state model for partially crystalline systems.However, such experiments should be undertaken with caution as the mixed two-state material can sometimes have significantly different properties from the partially crystalline material that is manufactured directly (the real one-state system). ... 

Armstrong, N.A. Lowndes, D.H.L. The use of mixtures of spray dried lactose and microcrystalline cellulose as direct compression excipients. Int. J. Pharm. Technol. Prod Manuf. 1984,5(3), 11-14. 

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