Microcrystalline cellulose interactions

This focus on residues associated with microcrystalline cellulose is not to denigrate it as an excipient. It is and will remain a most valuable formulation aid that can help compression, disintegration, and flow, as well as acting as a general diluent in solid-dose for-mulation. It can also be a useful additive in liquid products. Indeed, the knowledge available on microcrystalline cellulose interactions probably reflects the level of interest in such a useful material. Rather, the intent is to illustrate how excipients, or residues contained in them, can interact with active ingredients in a number of ways. The first commandment for the... 

The essential difference between physical and chemical interactions is that in the former the interacting molecules are not chemically modified in any way. Hydrogen bonding may change, but there are no chemical changes that create a different molecule. However, this does not mean that the different components of the interaction can be easily separated the resultant mixture may be so intimate that separation is not possible. For example, silicified microcrystalline cellulose after processing cannot be separated entirely into its two separate components (fumed silica and microcrystalline cellulose). But on examination, using a number of vibrational spectroscopic methods, it was shown to be an intimate physical mixture and not a new chemical entity (8). 

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. 

Figure 8 also shows an example of moisture uptake for four selected excipients as a function of relative humidity. Depending on the hygroscopicity of the exscipi-ents, the uptake behaviors are quite variable. Excipients such as microcrystalline cellulose (MCC) and starch can pick up significant amounts of water at relatively low relative humidity. Since this water is not present as a hydrate, it is potentially free to interact with a drug. 

Various substances were added to formed coacervate systems to observe their effects. Added sodium dodecyl sulfate did not affect the coacervates. Microcrystalline cellulose particles, added to the coacervate system before and after the coacervates were formed, were observed to be too large to be incorporated in or interact with the coacervate drops. Coacervates made in glucose and sucrose solutions were unaffected by the sugar. 

Physical interactions between drug and excipient also can compromise quality. Adsorption of drug by microcrystalline cellulose resulted in drug dissolution being less than complete. Interaction between chloramphenicol stearate and colloidal silica during grinding led to polymorphic transformation. 

The resolution of optical antipodes on polysaccharides is mainly governed by the shape and size of solutes (inclusion phenomena) and only to a minor extent by other interactions involving the functional groups of the molecules. In the case of microcrystalline cellulose triacetate (MCTA), the type and composition of the aqueous-organic eluent affect the separation because these result in different swelling of MCTA. 

Rowe RC. Interaction of lubricants with microcrystalline cellulose and anhydrous lactose—a solubility parameter approach. Int J Pharm 1988 41 223-226. 

The role of CBMs may not be entirely passive, although thermodynamics ensure that any interaction has to be stoichiometric rather than catalytic. An isolated CBM 2a, originally from a Cellulomonas fimi endoglucanase, formed the usual (3-sandwich, but, in solution, when unconstrained by an attached catalytic domain, dimerised." This CBM liberated small particles from cotton linters but not bacterial microcrystalline cellulose the same behaviour was shown by the holoenzyme which had been inactivated with the appropriate Withers inactivator." " However, another CBM 2a, from Cellvibrio japonicus, was rigorously shown to act only by increasing substrate proximity." ... 

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. 

In a system (pharmaceutical tablet) composed of a compressed core material A (e.g. microcrystalline cellulose or anhydrous lactose) the value of the interaction parameter provides a good prediction of the mode of failure of the system, i.e. interfacial or cohesive within the weaker component. Table 12 presents values for and omax(B/A). 

In all cases, microcrystalline cellulose yielded a slightly higher interaction value and a maximum adhesive strength. Systematically cellulose acetate gave also higher values than EC. Should the interaction coefficient be equal or close to unity, an interfacial failure would not be possible. 

Microcrystalline cellulose triacetate, cyclodextrin- and crown ether-derived CSPs, as well as some chiral synthetic polymers, achieve enantiomer separation primarily by forming host-guest complexes with the analyte in these cases, donor-acceptor interactions are secondary. Solutes resolved on cyclodextrins and other hydrophobic cavity CSPs often have aromatic or polar substituents at a stereocenter, but these CSPs may also separate compounds that have chiral axes. Chiral crown ether CSPs resolve protonated primary amines. 

L.F. Vieira Ferreira, J.C. Netto-Ferreira, I.V. Kmelinskii, A.R. Garcia, and S.M.B Costa, "Photochemistry on surfaces matrix isolation mechanisms for study of interactions of ben-zophenone adsorbed on microcrystalline cellulose investigated by diffuse reflectance and luminescence techniques", Langmuir, Vol. 11, pp. 231-236,1995. 

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. 

We would like to stress here the importance of X-ray photoelectron spectroscopy (XPS) for surface characterization, since it analyzes the first 10 or 20 atomic monolayers. It gives information regarding both composition and elemental concentration, as well as the probe-surface interactions. Quite recently [15, 16], this technique allowed the authors to study rhodamine and cyanine dyes physically and/or chemically bound to microcrystalline cellulose. 

The swelling of cellulose in the presence of moisture is a well known property of this material. Other protic and nonprotic solvents such as methanol, ethanol, acetonitrile, and acetone also have the capacity to swell microcrystalline cellulose. However, solvents such as benzene, toluene, or dichloromethane do not promote this effect. Therefore it is possible to control adsorption of probes on microcrystalline cellulose, either on the surface or entrapped within the natural polymer chains. After the removal of the solvent used for sample preparation, and for a swelling solvent, a chain-guest-chain interaction is promoted, replacing the previous chain-solvent-chain interaction. 

By studying simple cyanines adsorbed onto microcrystalline cellulose it was possible to get some insight into the nature of the interactions of these cyanines with the polymer chains, namely in regard to the importance of hydrogen bonding of the probe to the substrate, which is of major importance in the immobilization process, and in minimizing the nonradiative transitions of the excited states. 

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