Anionic mucoadhesive polymers as auxiliary agents for the peroral administration of (poly)peptide drugs: influence of the gastric juice.
The incorporation of (poly)peptide drugs in mucoadhesive polymers is a promising strategy for their peroral administration. In this study, the protective effect of various polymers toward an artificial gastric fluid and the influence of an enteric coating on the adhesive properties have been investigated. Tablets containing 30 mg of carbomer (C934P), neutralized carbomer (NaC934P), or sodium carboxymethylcellulose (NaCMC), 0.1 mg of the model protein peroxidase, and 19.9 mg of mannitol were incubated at 37 degrees C for 2.5 hr with a simulated gastric fluid with and without pepsin. All polymers--although anionogenic--displayed quick swelling behavior in the acid milieu, leading to an unintended protein release. Moreover, pepsin is capable of penetrating into the polymeric carrier systems, thereby rapidly degrading the embedded protein. Enteric coating, on the other hand, leads to strongly reduced adhesive properties. Only NaC934P tablets coated with polymethacrylate containing 9% triethylcitrate displayed no significant (p < .05) reduction in adhesive strength. Results give essential basic information for the development of peroral (poly)peptide dosage forms based on mucoadhesive polymers.
Bernkop-Schnürch
A
A
Center of Pharmacy, Institute of Pharmaceutical Technology, University of Vienna, Austria. andreas.bernkop-schnuerch@univie.ac.at
Gilge
B
B
D000284:Administration, Oral; D000838:Anions; D004304:Dosage Forms; D015195:Drug Design; D005750:Gastric Juice / Q000737:chemistry*; D005753:Gastric Mucosa / Q000502:physiology; D006801:Humans; D010434:Pepsin A / Q000494:pharmacology*; D010455:Peptides / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D011108:Polymers
D000838:Anions; D004304:Dosage Forms; D010455:Peptides; D011108:Polymers; D010434:Pepsin A