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linked carboxymethyl ether of starch (USP 32/NF 27 and JP XVI). Three types of SSG are specified in Ph. Eur. 8.3, and two types are specified in USP 32/NF 27 and JP XVI (Table 1). Type A and Type B differ in the degree of neutralization of the car- boxymethyl groups, and Type C is prepared by physical dehydration. According to the FDA's inactive ingredient database (IID), SSG is us ed i n various pharmaceutical dosage forms, including immediate- and delayed-release tablets, capsules (e.g., with coated pellets), and in more advanced formulations, such as multilayer tablets and orally disinte- gr ati ng tablets (ODTs). Usage ranges from 2 milligrams to 876 mil- ligrams per tablet/capsule, but it is typically around 26 milligrams. The pharmacopieal definition of SSG allows manufacturers to use dif- ferent synthetic methods of produc- tion, which leads to the chemical and impurity differences between products. Synthesis from native starch is a two-step process: cross- linking and carboxymethylation, and the steps can be performed in any order. (The sequence of the steps is unrelated to the pharmacopoeial types of SSG.) Primojel, for exam- ple, is made by carboxymethylation of a cross-linked starch derivative, which has no effect on the starch granule's original shape. The type of cross-linking, however, can affect th e chem i cal stability of SSG. P hos pha te- ester cross-links are chemically stronger than the car- boxyl cross-links, which may be sus- ceptible to hydrolysis. In addition, the degree of cross-linking affects both the swelling volume and the soluble fraction, thereby affecting functionality. Functionally, SSG swells in three dimensions in water, and CCS swells in two dimensions. While XP does not absorb very much water nor swell greatly, it develops a high dis- integrating force. The mechanism is thought to be wicking and shape recovery after deformation during tablet compression. Traditional applications in pharma- ceutical formulations Tablet disintegration is complex and m any f actors i nfluence i t, including the disintegrant's mode of action, the type of tablet matrix (hydrophilic/hydrophobic), the API's properties, and the tablet's porosity. Because of the interplay of factors, it is impossible to make a general rule that a certain type of superdisinte- grant is preferred for rapid disinte- gration and dissolution. When a tablet contains large proportions of highly soluble materials (API or excipient), then the swelling or shape recovery mechanism may not allow an effective disintegrating force to develop because the tablet matrix "dissolves" away from the dis- integrant. In such cases, the ability of a superdisintegrant (e.g., CCS) to draw water into the tablet (by wick- ing) m ay b e t he key f actor. Conversely, w hen a n insoluble matrix is used, either swelling or shape recovery is the principle rea- son to choose SSG. SSG's performance has been stud- ied in a variety of OSDFs as far back as the 1970s and it's still being stud- ied today [5, 6]. The amount of SSG and the type of addition (intra- or extra-granular or a 50-50 split (w/w) of t he t wo) m ust be optimized according to the tablet's composition and the target disintegration profile for the product. SSG can be coupled with a matrix that comprises di-cal- Figure 2 Superdisintegrant use in combination with MCC and lactose [4] 25 CCS SSG XP % of formulations MCC+ Lactose+ 20 15 10 5 0 Table 1 Key differences in SSG grades, types A, B, and C Property Type A Type B Type C Identification by IR Ph. Eur. 8.3 USP 32-NF 17 JP XVI Not included Included Included Not included Included Included Not included No monograph No monograph Assay Ph. Eur. 8.3 USP 32-NF 17 JP XVI 2.8 - 4.2% 2.8 - 4.2% 2.8 - 4.2% 2.0 - 3.4% 2.0 - 3.4% 2.0 - 3.4% 2.8 - 5.0% No monograph No monograph pH Ph. Eur. 8.3 USP 32-NF 17 JP XVI 5.5 - 7.5% 5.5 - 7.5% 5.5 - 7.5% 3.0 - 5.0% 3.0 - 5.0% 3.0 - 5.0% 5.5 - 7.5 No monograph No monograph 36 October 2015 Tablets & Capsules