Crospovidone

The crospovidones are easily compressed when anhydrous but readily regain their form upon exposure to moisture. This is an ideal situation for use in pharmaceutical tablet disintegration and they have found commercial appHcation in this technology. PVP strongly interacts with polyphenols, the crospovidones can readily remove them from beer, preventing subsequent interaction with beer proteins and the resulting formation of haze. The resin can be recovered and regenerated with dilute caustic. 

One practical result of this strong interaction is the employment of PVP to remove unwanted phenoHcs such as bitter tanins from beer and wine. This process is more easily carried out with insoluble crospovidone, which can be regenerated for reuse with dilute base (104). Soluble PVP has been employed to prevent photoyeUowing of paper by complexing free phenoHc hydroxyl groups in lignin (105). 

E. Barabas and C. Adeyeye, "Crospovidone," Anal Profiles Drug Subst. Excipients, 24, 87—163 (1996). 

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

Crospovidone is a cross-linked homopolymer of A-vinyl-2-pyrrolidone. Acetylene and formaldehyde react to form butynediol. Hydrogenation and subsequent cyclodehydrogenation gives butyrolactone. The reaction of butyrolactone with ammonia produces pyrrolidone, which is vinylated with acetylene under pressure. The linear polymerization of the vinylpyrrolidone yields polyvinylpyrrolidone, a soluble binder, whereas the popcorn (branched) polymerization yields crospovidone, an insoluble... 

The ability of a disintegrant to draw water into the porous network of a tablet is essential for effective disintegration. For crospovidone, water wieking has been thought to be the main meehanism of disintegration. Komblum and Stoopak [5] ob-... 

FIG. 3. Scanning electron photomicrographs of crospovidones (A) Crospovidone M, (B) Kollidon CL, (C) Polyplasdone XL-10, and (D) Polyplasdone XL. 150X Magnification. 

No filler Crospovidone Equal > intra > extra fastest disintegration and dissolution. 

Hartauer et al. [58] reported that peroxide residues in povidone (binder) and crospovidone (disintegrant) were attributable to the formation of the A-oxide oxidation product of raloxifene. The authors correlated residual levels of peroxide in the excipients with A-oxide formation and thereby gained understanding of the degradation mechanism. A radical-initiated oxidation mechanism would be expected to show a typical S -shaped autocatalytic curve, whereas these curves showed fickian kinetics that is, rapid initial formation of the A-oxide followed by a plateauing of the rate, with consumption of the peroxides, leading to a slowing of the reaction rate. 

Tablets were prepared either with an insoluble (dicalcium phosphate dihydrate), a soluble (6-lactose) or a moderately soluble filler-binder (a-lactose monohydrate). As a disintegrant four different starches (com, rice, potato and tapioca) were used. As a comparison the effect of two super-disintegrants (crospovidone and sodium starch glycolate) was studied. The disintegrants were added at two concentration levels. The compression load was adjusted in order to obtain tablets with comparable initial cmshing strengths.

The four starches used in this study have been proven to be suitable tablet ingredients [19]. Both used super-disintegrants, Primojel (sodium starch glycolate) and Polyplasdone XL (crospovidone), are commonly used as a disintegrant in tablets prepared by direct compression. 

The initial disintegration times of the tablets prepared with a-lactose were excellent all tablets disintegrated within 2 minutes. The 6-lactose tablets showed longer, but still adequate disintegration times. The difference between the effectiveness of sodium starch glycolate and crospovidone in 6-lactose tablets was previously studied by Van Kamp et al. [24] and ascribed to the higher capillary action of crospovidone. 

CS = Com starch PS = Potato starch RS = Rice starch TS = Tapioca starch PR = Na-starch glycolate PV = Crospovidone... 

Irrespective of the filler-binder used, in tablets prepared with crospovidone as a disintegrant, all three adjustable factors influenced the SIR of crushing strength. Also the interaction between the concentration and the relative humidity was significant (y0i3,siR(s) 0)-... 

Each combination behaves differently after storage. In all cases there was an effect of the starch concentration (y i sir(d) is significant). In most cases the relative humidity as well as the interaction between the relative humidity and the disintegrant concentration plays a role in the disintegration time of tablets prepared with either lactose. The dicalcium phosphate dihydrate/rice starch combination is influenced very strongly by the three factors studied. This combination is not suitable for use in tropical countries. Neither is the combination of B-lactose and crospovidone. 

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