title: Peroral delivery systems based on superporous hydrogel polymers: release characteristics for the peptide drugs buserelin, octreotide and insulin.
abstract: Novel peroral peptide drug delivery systems based on superporous hydrogel (SPH) and SPH composite (SPHC) have recently been developed in our laboratory. In this report the following issues were studied: release of the peptide drugs buserelin, octreotide and insulin from SPH and SPHC polymers and the developed delivery systems, stability of these peptides during the release and the integrity of insulin in the polymeric matrix of SPHC. Release studies from SPH and SPHC polymers revealed that buserelin, octreotide and insulin were released almost completely from the polymers. Peptide release rates from SPH were faster than from SPHC, due to the more porous structure of SPH polymer. All peptides studied in contact with SPHC polymer were stable under different environmental conditions (ambient temperature, 37 degrees C, light and darkness and at pH values 3.2 and 7.2). FTIR studies demonstrated that no covalent binding occurred between insulin and the polymeric SPHC matrix. Release profiles of all peptides from the developed delivery systems showed a time-controlled release profile: after a short lag time of 10-15 min, a burst release of peptides occurred during which more than 80% of peptide was released within 30-45 min. In conclusion, the present delivery systems based on SPH and SPHC show appropriate in vitro properties for application in peroral peptide drug delivery of buserelin, octreotide and insulin, and are therefore promising for further in vivo evaluation.
authors.affiliation: Department of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box 9502, The Netherlands.
authors.forename: Farid A
authors.initials: FA
authors.lastname: Dorkoosh
authors.forename: J
authors.initials: J
authors.lastname: Coos Verhoef
authors.forename: Matheus H C
authors.initials: MH
authors.lastname: Ambagts
authors.forename: Morteza
authors.initials: M
authors.lastname: Rafiee-Tehrani
authors.forename: Gerrit
authors.initials: G
authors.lastname: Borchard
authors.forename: Hans E
authors.initials: HE
authors.lastname: Junginger
mesh_terms: D002064:Buserelin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015282:Octreotide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics; D011108:Polymers / Q000008:administration & dosage / Q000493:pharmacokinetics; D016062:Porosity / Q000187:drug effects
chemical_list: D020100:Hydrogels; D007328:Insulin; D010455:Peptides; D011108:Polymers; D002064:Buserelin; D015282:Octreotide