Protective Effect of Carbopol on Enzymatic Degradation of a Peptide-Like Substrate I: Effect of Various Concentrations and Grades of Carbopol and Other Reaction Variables on Trypsin Activity

• Published in: Pharmaceutical development and technology 2007, Vol.12 (1), p.89-96
• Main Authors: Vaidya, A.P., Wigent, R.J., Moore, J.C., Schwartz, J.B.
• Format: Article
• Language: English
• Subjects: Acrylic Resins; Animals; Arginine - analogs & derivatives; Arginine - chemistry; Biological and medical sciences; Cattle; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; enzymatic hydrolysis; enzyme inhibition; General pharmacology; Hydrogen-Ion Concentration; Hydrolysis; ionic strength; mechanism of inhibition; Medical sciences; Peptides - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyvinyls - chemistry; Polyvinyls - pharmacology; Trypsin - chemistry; Trypsin Inhibitors; Viscosity
• ISSN: 1083-7450; 1097-9867
• DOI: 10.1080/10837450601168656

The purpose of this study was to determine and compare the effect of various concentrations and grades of Carbopol on trypsin-induced degradation of a prototype substrate, Nα-benzoyl-L-arginine ethyl ester hydrochloride (BAEE). Effect of other reaction variables, such as viscosity and ionic strength of the medium on the trypsin activity, was also analyzed simultaneously. Four concentrations and three commercially available grades of Carbopol were used. The effect of Carbopol was expressed in terms of change in the velocity of degradation reaction. A modified trypsin assay was developed and used for analysis. Up to a concentration of 0.35% w v, Carbopol® 934P showed a concentration-dependent increase in its ability to reduce the rate of enzymatic hydrolysis of BAEE. Similar inhibitory effect was observed with all three grades of Carbopol. The activity of trypsin was unaffected by other reaction variables, suggesting that interaction between the protein and the polymer could be the mechanism responsible for reduced trypsin activity. This study suggests that Carbopol can be a useful excipient for oral delivery of bioactive proteins and peptides, due to its ability to reduce the enzyme-induced degradation of these agents.