The issue of peroxide contamination in crospovidone was recently underscored when the US Food and Drug Administration issued
an advisory to manufacturers of drugs and dietary supplements to apprise them of a contaminated lot of crospovidone from a
Chinese supplier (2). The peroxide level found by FDA in the lot was more than four times the maximum level of peroxide (400
ppm) allowed by global compendial monographs. FDA issued the advisory because it was "concerned that drug manufacturers using
excipients containing high levels of peroxides will observe a loss of drug potency and the formation of excessive impurities
during the product shelf life" (2). FDA advised manufacturers to use sound risk-management principles when working with a
supplier of crospovidone to ensure the quality of the product.
In terms of functionality, commonly used superdisintegrants such as crospovidone, croscarmellose sodium, and sodium starch
glycolate are effective at low concentration levels (2–5 w/w%) in tablet formulation by facilitating the rate and extent of
tablet disintegration (3). Bee points out, however, that although these excipients are often comparable with respect to disintegration,
there can be differences in dissolution. As a nonionic compound, crospovidone can be more effective with cationic active ingredients,
an advantage compared with anionic disintegrants such as croscarmellose sodium and sodium starch glycolate, which would interact
with the cationic actives and potentially retard dissolution. In one recent study, for example, ISP evaluated the respective
effects of crospovidone, croscarmellose sodium, and sodium starch glycolate on the dissolution behavior of eight cationic
drugs from a model direct-compression tablet formulation with 2% w/w superdisintegrant (3). Although no significant differences
were observed in the disintegration times of the tablets, the study showed that actives formulated with crospovidone showed
a more rapid dissolution rate than the same drugs formulated with other superdisintegrants for the cationic drugs studied,
irrespective of the drug's aqueous solubility (3).
In a separate study, ISP evaluated the impact of the superdisintegrant on the dissolution of 13 poorly soluble drugs (4).
Although no significant differences were observed in the disintegration times of the tablets, the study showed that actives
formulated with crospovidone showed a more rapid dissolution rate than the same drugs formulated with other superdisintegrants
for 12 of the 13 poorly soluble drugs studied.
Sources
1. Ph. Eur. 7.0 (Strasbourg, France), 1771–1773 (2011).
2. FDA, "Advisory to Drug and Dietary Supplement Manufacturers, Compounding Pharmacies and Distributors of Excipients and
Dietary Ingredients—FDA Detects High Levels of Peroxide in Crospovidone" (Rockville, MD, Oct. 21, 2010).
3. J. Balasubramaniam et al., Dissolution Technol. 15 (2), 18–25 (2008).
4. J. Balasubramaniam and T. Bee, Pharm. Technol.
33 (4) supp. Excipient Performance for Solid Dosage Forms, s6–s14 (2009).
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