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eye on used worldwide as a superdisinte- grant in pharmaceuticals and dietary supplements. It is a natural product that is free of sugar and starch. The manufacture of croscarmellose sodium starts with cellulose, usually from wood pulp or cotton linter. The cellulose molecule contains repeti tive units of cellobiose, which comprises two units of glucose anhydride that are joined by ß-linkages. These units con- tain three hydroxyl groups capable of reacting, which permits a substitution with carboxy methyl groups. Figure 1 shows the molecular structure of native cellulose. Croscarmellose sodium is a product of the alkali-catalyzed reaction of cel- lulose with sodium monochloroacetate under rigidly controlled conditions. During the reaction, the carboxyl groups from the acid substitute the hydroxyl groups, and the formerly insoluble cellulose becomes a soluble and chemically reactive intermediate. The number of hydroxyl groups involved in the substitution determines the degree of substitution (DS) of the product. According to compendial monographs, the DS should be between 0.60 and 0.85. The substi- tuted intermediate molecule undergoes internal cross-linking without the addition of cross-linking additives. It's this cross-linking that controls solubil- ity and promotes the swelling of the product, which enables it to absorb many times its weight in liquid. In a final step, the cross-linked product is purified, dried, and comminuted to decrease the particle size and narrow the particle size distribution. Figure 2 shows the structure of croscarmellose sodium, and Figure 3 shows an image of it taken through a scanning electron microscope. Application The mechanism of action of croscarmellose sodium in a tablet starts when it swells, which is highly dependent on the penetration of a liquid into the tablet. The swelling breaks the tablet's binding forces, causing it to disintegrate and thereby accelerating the dissolution of the active pharamaceutical ingredient (API). Its level of use ranges from 0.5 to 5 percent, but 0.5 to 2 percent is sufficient in most formulations. Tablets & Capsules May 2014 37 Valdemir Passos Blanver excipients In this installment, guest columnist Val - de mir Passos describes how croscarmel- lose sodium is made and offers advice about its use in combination with tablet binders and lubricants. Never hesitate to ask your excipi- ent manufacturer about the products it supplies. Asking questions is funda- mental to gaining the full benefit of the excipients you use. It also enables your supplier to help you select the excipients that are most appropriate for your formulation. That's important because there are certain excipients that exhibit spe- cific characteristics and behaviors that are not completely addressed by compendial specifications. Only by having an open, direct discussion with your supplier can you learn about these characteristics, which will clarify important aspects about the excipient manufacturing process, the control of byproducts or solvent residues that may be present, use lev- els, performance in different dosage forms, and behavior when mixed with other excipients. With that in mind, here are some guidelines about using croscarmellose sodium in the manufacture of phar- maceutical tablets that are not pro- vided in compendial monographs or specifications. First, let's discuss how croscarmellose sodium is made. Manufacture of croscarmellose sodium Croscarmellose sodium is the so - dium salt of a cross-linked, partly O- (carboxymethylated) cellulose and is Figure 1 Molecular structure of cellulose H H CH 2 OH H O HO H H H H O OH OH CH 2 OH OH H H H OH O H H CH 2 OH H O HO H H H H O OH OH CH 2 OH OH H H OH n O H j-EOE_36-41_Masters 5/14/14 10:18 AM Page 37