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Effects of Polyacrylic Polymers on the Lumenal Proteolysis of Peptide Drugs in the Colon

Journal of Pharmaceutical Sciences, ISSN: 0022-3549, Vol: 84, Issue: 11, Page: 1291-1294
1995
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□ The in-vitro effectiveness of polyacrylic acid polymers in inhibiting degradation of insulin, calcitonin, and insulin-like growth factor-l by colonic lumenal contents was determined. Further, the effect of Carbopol 974P, a polyacrylic acid polymer, on colonic absorption of insulin in rats was studied. The results revealed that Carbopol 934P, 971P, and 974P all strongly inhibited microbial proteolytic activities against insulin, calcitonin, and insulin-like growth factor-l. Inhibition by Carbopol polymers was complete or almost complete when the concentration of each polymer in saline or in 50 or 100 mM Tris buffer was 0.4%, where the pH of the medium was lower than 5. The extensive inhibition by these polyacrylic acid polymers seems to correlate with their ability to acidify the incubation medium. Further, in-situ absorption studies showed that Carbopol 974P increased the pharmacological availability of colonic insulin. In summary, Carbopol polymers are useful in minimizing colonic proteolysis of peptide drugs.

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