Microcrystalline cellulose pharmaceutical excipient

Moreton RC. Cellulose, silicified microcrystalline. In Kibbe AH ed. Handbook of Pharmaceutical Excipients. Washington, D.C. American Pharmaceutical Association and London Pharmaceutical Press, 2000 110-111. 

For the pharmaceutical product development scientist, there is clearly a need for objective information about the practical performance of different excipients and their various grades. In this chapter we set out to bring together the results of some of our ongoing evaluations of the physical and mechanical properties of excipients commonly used for the manufacture of solid oral dosage forms. In this particular article, we have chosen to focus on the fillers that are most commonly used in the manufacture of immediate release tablets microcrystalline cellulose (MCC), lactose, calcium phosphate, and mannitol (1). 

Research on nasal powder drug delivery has employed polymers such as starch, dextrans, polyacrylic acid derivatives (e.g., carbopol, polycarbophil), cellulose derivatives (microcrystalline cellulose, semicrystalline cellulose, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose), chitosan, sodium alginate, hyaluronans, and polyanhydrides such as poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA). Many of these polymers have already been used as excipients in pharmaceutical formulations and are often referred to as first-generation bioadhesives [38-45], In nasal dry powder a single bioadhesive polymer or a... 

SEPIFILM 003 and 752 The association of cellulose with a film coating agent was originally patented by SEPPIC. Microcrystalline cellulose is probably one of the most extensively used excipients in pharmaceutical and nutritional products. Unlike other fillers, such as lactose, cellulose is inert, vegetable derived, and accepted worldwide and its shelf life is unlimited. Figure 31 shows the advantage of cellulose microcrystalline in film coating. 

A great many of the materials that are used as pharmaceutical excipients occur naturally in the amorphous or partially amorphous state (e.g., gelatin and starch). Many others have been found to possess improved handling and mechanical properties when processed in such a manner as to render them at least partially amorphous. Examples of this include the grades of microcrystalline cellulose and lactose monohydrate used as pharmaceutical tableting diluents. ° ... 

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). ... 

Since its introduction as a direct compression diluent in 1964, microcrystalline cellulose has become a pharmaceutical excipient of great importance. It consists... 

Microcrystalline cellulose is not absorbed systemically following oral administration and thus has little toxic potential. Consumption of large quantities of cellulose may have a laxative effect, although this is unlikely to be a problem when cellulose is used as an excipient in pharmaceutical formulations. 

Molecules of low molecular weight (e.g., drugs) are likely to adsorb to polymers present in the formulation. Adsorption occurs by the formation of weak (localized) interactions, hydrogen bonds, or ionic bonds between molecules and polymers. Microcrystalline cellulose, which is an important pharmaceutical excipient, has been demonstrated to influence chemical and photochemical reaction mechanisms of adsorbed compounds (Wilkinson et al., 1991). Interactions between drugs and polymeric compounds and the subsequent influence on photoreactivity are further discussed in Chapter 15. 

Because many of the pharmaceutical excipients used in the formulation of racemic drugs are chiral and optically pure, there is a potential for the stereoselective interaction of the enantiomers with the chiral matrix included in the formulation. For example, enantioselective pH-dependent release of tiaprofenic acid enantiomers from a sustained release formulation containing microcrystalline cellulose has been reported [260]. The differential release of tiaprofenic acid enantiomers, however, did not alter the pharmacokinetics of the individual enantiomers in rats. The possible effects of chiral excipients on the stereoselective release of racemates are discussed in a separate chapter in this book. 

Kibbe, A.H. Handbook of Pharmaceutical Excipients Cellulose, Silicified Microcrystalline American Public Health Association Washington, DC, 2000. 

Builders, R.F. Agbo, M.B. Adelakun, T Okpako, L.C. Attama, A.A. Novel multifunctional pharmaceutical excipients derived from microcrystalline cellulose-starch microparticulate composites prepared by compatibilized reactive polymer blending. Int. J. Pharm. 2010, 388 (1-2), 159-167. 

The most important incompatibility in capsules is the adsorption of active substances to excipients and vice versa. Sparingly water-soluble active substances may adsorb to non-water soluble excipients such as microcrystalline cellulose (diluent). On the other hand, the very fine glidant, colloidal anhydrous silica, can adsorb onto active substance particles. Especially for low dosed active substances, relatively large fractions may adsorb or be adsorbed. Such adsorption may delay the dissolution of the active substance, resulting in a delayed or incomplete release of the substance. This may lead to a reduced pharmaceutical availability and ultimately a lower therapeutic activity. Substances known to adsorb to microcrystalline cellulose are ethinylestradiol and dexamethasone [24]. 

The first detailed description of the drying of products in spray form was mentioned in a patent of 1872 entitled Improvement of Drying and Concentration of Liquid Substances by Atomizing (2). However, this process found its first significant applications in the milk and detergent industries in the 1920 s (3). In current times, spray drying is utilized extensively in many aspects of our daily life from food products, cosmetics, and pharmaceuticals to chemicals, fabrics, and electronics. Typical pharmaceutical examples include spray-dried enzymes (such as amylase, protease, lipase, and trypsin), antibiotics (such as sulfathiazole, streptomycin, penicillin, and tetracycline) and many other active pharmaceutical ingredients, vitamins (such as ascorbic acid and vitamin B12), and excipients for direct compression (such as lactose, mannitol, and microcrystalline cellulose). 

Schmidt and coworkers have carried out determinations of the surface acidity of pharmaceutical excipients and used a variety of absorption indicators to span the ranges of observed the acid strengths. In one study, the surface acidity of microcrystalline cellulose and dicalcium phosphate anhydrate was evaluated using thymol blue, bromcresol green, bromcresol purple, and phenol red as the absorption indicators. " Using the pH dependence of dye absorbance published in the paper, it was concluded that Hq was approximately 1.0 for dicalcium phosphate anhydrate, and approximately 4.0 for microcrystalline cellulose. 

By foregoing use of the end cap, core sampler performance is improved further. In Figure 15-7 we display core sampling resnlts for three different inner-diameter sampling tubes using a two-layer bed of common pharmaceutical excipient powders microcrystalline cellulose and lactose. For aU sampler diameters, the experimental data are indistinguishable from ideal expected concentrations. In practice, we note that it is important that the walls of the sampling tubes be... 

Starch and its derivatives are also favourable in pharmaceutics being an alternative for microcrystalline cellulose as an excipient intended for the production of pellets via extrusion-spheronization. Dukic et reported the application of a specific grade of modified starch for extrusion-spheronization purposes a crystalline, high-amylose starch formed by gelatinization of amy-lose-rich starches, followed by enzymatic debranching of amylopectin molecules and retrogradation of linear amylose chains, produces a potential candidate. ... 

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