Microcrystalline cellulose excipients

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. 

The sorption of water by excipients derived from cellulose and starch has been considered by numerous workers, with at least three thermodynamic states having been identified [82]. Water may be directly and tightly bound at a 1 1 stoichiometry per anhydroglucose unit, unrestricted water having properties almost equivalent to bulk water, or water having properties intermediate between these two extremes. The water sorption characteristics of potato starch and microcrystalline cellulose have been determined, and comparison of these is found in Fig. 11. While starch freely adsorbs water at essentially all relative humidity values, microcrystalline cellulose only does so at elevated humidity values. These trends have been interpreted in terms of the degree of available cellulosic hydroxy groups on the surfaces, and as a function of the amount of amorphous material present [83]. 

Formuiation The formulation consists of excipients such as carnauba wax, crospovidone, hydroxylpropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate, microcrystalline cellulose, and other inactive ingredients. 

Spherical pellets containing 5% triamcinolone acetonide were prepared by Villar-Lopez and co-workers [59] by extrusion/spheronization following formulation with microcrystalline cellulose and/or a hydrophilic excipient like lactose, sodium earbox-ymethylcellulose, or P-cyclodextrin. Their suitability for coating, with a view toward colonic drug deliveiy, was assessed in terms of their size, sphericity, and dissolution test response. The best results were afforded by a 5 90 5 composition of microcrystalline cellulose, P-cyclodextrin, and triamcinolone acetonide, prepared by complex-ation of triamcinolone acetonide with P-cyclodextrin prior to the addition of microcrystalline cellulose. 

Dissolution profiles from tablets containing 60% theophylline and 25% microcrystallme cellulose showed a smaller difference in the release rate of theophylline from heated and non-heated tablets (Fig. 3). Nevertheless, both of these tablets demonstrated a matrix-controlled release. These results suggest that the level of excipient in the tablet exerted a significant effect on the dissolution release properties of thermally and non-thermally treated tablets. As the microcrystalline cellulose content increased, the difference in release rates between heated and non-heated tablets became more pronounced. 

In this chapter, analysis of the excipient in Nasonex (mometasone naral spray) is used as a typical example to demonstrate how to select a proper analytical method. Nasonex Nasal Spray contains Mometasone Furoate, microcrystalline cellulose, and carboxymethylcellulose sodium NF, citric acid USP, sodium citrate USP, benzalkonium chloride solution NF, glycerin USP, polysorbate 80 NF, phenylethyl alcohol USP, and water USP. 

Sherwood BE, Becker JW. A new class of high functionality excipients silicified microcrystalline cellulose. Pharm Tech 1998 22(10) 78—88. 

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). 

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). 

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. 

Other examples of the use of microcalorimetry to study drug-excipient compatibility in the solid state are provided by Selzer et al. (30), who studied the interaction between a solid drug and a range of excipients [including potato starch, a-lactose-monohydrate, microcrystalline cellulose (MCC), and talc] and Schmitt (31) who used water slurries instead of humidified samples. 

Some excipients contain a certain amount of amorphous form such as spray-dried lactose,27 and others are hygroscopic, such as microcrystalline cellulose.28 These excipients will adsorb water, which causes a change in the micro-environment of the formulation. If the drug substance is moisture-sensitive, degradation may occur quickly. Therefore, consider both drug-excipient compatibility and excipient impurity profile in selecting excipients for low-dose drug products. 

However, some excipients have multiple functions. For example, microcrystalline cellulose can function as a filler, a binder, and a disintegrant. As seen in Table 7.3, a typical low-dose formulation could include more than 85% filler—binders. Thus, physical and chemical properties for these specialty excipients are extremely important in a low-dose formulation for manufacturability, product performance, and longterm stability. Because the poor physicomechanical properties of components are not altered during manufacture as they are in the wet or dry granulation process, critical material properties and their impact on product quality attributes should be well characterized and understood.23 Discussion in this section will focus on fillers-binders. For those requiring more information on excipients, several excellent books and review articles are available in the literature.24-27... 

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... 

Cel-O-Cal—an excipient consisting of microcrystalline cellulose and calcium sulfate ... 

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