Cellulose microcrystalline particles

C. G6mez Hoyos, E. Cristia, and A. Vazquez, Effect of cellulose microcrystalline particles on properties of cement bcised composites, Mater. Des. 51,810-818 (2013). 

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. 

Another form of cellulose, microcrystalline cellulose, has been used for pharmaceutical applications. Microcrystalline cellulose is a nonhbrous form of cellulose in which the cellulose fibers are fragmented into particle forms ranging in size from... 

The cellulose derivatives contained all three —OH groups of each glucose unit replaced by carbamate bonds. For the preparation of plates, 300 mg of each derivative (particle size 10-100 /rm) and 300 mg of cellulose microcrystalline were mixed with 3 ml water and a small amount of ethanol, as wetting agent, to obtain a suspension that was stratified on 2.6 x 7.6 cm glass microslides. Plates were dried in an oven at 105 C for 5 min to obtain layers having a thickness of about 0.25 mm [36],... 

Cellulose layers are produced from native, fibrous or microcrystalline cellulose (Avicel ). The separation behaviors of these naturally vary, because particle size (fiber length), surface, degree of polycondensation and, hence, swelling behavior are all different. 

The second system studied was the separation of the chiral epoxide enantiomers (la,2,7,7a-tetrahydro-3-methoxynaphth-(2,3b)-oxirane Sandoz Pharma) used as an intermediate in the enantioselective synthesis of optically active drugs. The SMB has been used to carry out this chiral separation [27, 34, 35]. The separation can be performed using microcrystalline cellulose triacetate as stationary phase with an average particle diameter greater than 45 )tm. The eluent used was pure methanol. A... 

The competitive adsorption isotherms were determined experimentally for the separation of chiral epoxide enantiomers at 25 °C by the adsorption-desorption method [37]. A mass balance allows the knowledge of the concentration of each component retained in the particle, q, in equilibrium with the feed concentration, < In fact includes both the adsorbed phase concentration and the concentration in the fluid inside pores. This overall retained concentration is used to be consistent with the models presented for the SMB simulations based on homogeneous particles. The bed porosity was taken as = 0.4 since the total porosity was measured as Ej = 0.67 and the particle porosity of microcrystalline cellulose triacetate is p = 0.45 [38]. This procedure provides one point of the adsorption isotherm for each component (Cp q. The determination of the complete isotherm will require a set of experiments using different feed concentrations. To support the measured isotherms, a dynamic method of frontal chromatography is implemented based on the analysis of the response curves to a step change in feed concentration (adsorption) followed by the desorption of the column with pure eluent. It is well known that often the selectivity factor decreases with the increase of the concentration of chiral species and therefore the linear -i- Langmuir competitive isotherm was used ... 

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. 

Measurements of particle porosity are a valuable supplement to studies of specific surface area, and such data are particularly useful in the evaluation of materials used in direct compression processes. For example, both micromeritic properties were measured for several different types of cellulosic-type excipients [53]. Surface areas by the B.E.T. method were used to evaluate all types of pore structures, while the method of mercury intrusion porosimetry used could not detect pores smaller than 10 nm. The data permitted a ready differentiation between the intraparticle pore structure of microcrystalline and agglomerated cellulose powders. 

Shotton et al. [38] Van Kamp et al. [39] Sulfadiazine (D) Povidone (B) No filler Prednisone (D) Maize starch Na calcium alginate Alginic acid Microcrystalline cellulose Colloidal aluminum silicate Extra > intra Extragranular incorporation yielded fastest disintegration, but intragranular incorporation yielded finer particles. Equal distribution of disintegrants is recommended. 

A.J. O Neil, R.D. Jee and A.C. Moffat, Measurement of the cumulative particle size distribution of microcrystalline cellulose using near infrared reflectance spectroscopy. Analyst, 124, 33-36 (1999). 

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). 

Figure 3 Examples of particle morphology for (A) microcrystalline cellulose, (B) lactose, (C) calcium phosphate dibasic, and (D) mannitol. Two images for each material representing different grades.

For nebulizer and other aqueous aerosol products that use suspension systems, excipients are used to influence particle physical and chemical stability (e.g., microcrystalline cellulose for nasal sprays). The suitability of the physicochemical properties of these critical excipients should be thoroughly investigated and documented (12). Far more excipients have been included in formulations designed for nasal administration (Table 4). 

Particle size distribution and surface area The particle size distribution of the drug may determine what grade of an excipient (e.g., microcrystalline cellulose) to use. 

Materials. All solvents were spectrophotometric grade (Aldrich) and were used without purification. Microcrystalline cellulose (Aldrich, 20 micron mean particle size) was used as supplied. 3,4-dimethoxyacetophenone (Aldrich) was purified by sublimation under vacuum at a pressure of 5 x lCH mBar at 40°C, purity being checked by melting point, UV-Visible and N.M.R. Spectroscopy. Phenol (Aldrich) and methoxybenzene (Aldrich) were used without further purification. 

Badawy SF, Gray DB, Hussain MA. 2006. A study of the effect of wet granulation on microcrystalline cellulose particle structure and performance. Pharm. Res. 23(3) 634-640. 

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... 

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