Pancreatin enhanced erosion of and macromolecule release from 2,2-bis(2-oxazoline)-linked poly(epsilon-caprolactone).
The degradation and erosion of solvent cast films and injection molded bars prepared from poly(epsilon-caprolactone) (PCL) and 2,2'-bis(2-oxazoline) linked poly(epsilon-caprolactone) (PCL-O) were evaluated in simulated gastric fluid (SGF) (pH 1.2, pepsin present) and in simulated intestinal fluid (SIF) (pH 7.5, pancreatin present). After incubation of the polymer films (10 mg) and bars (70 mg) in the medium, the resulting decrease in molecular weight (degradation) was determined by size exclusion chromatography and the weight loss of the preparations was measured. In addition, the effect of pancreatin on FITC-dextran (MW 4400) release from PCL and PCL-O microparticles, prepared by w/o/w double emulsion technique, was studied. No degradation or weight loss was observed for either PCL or PCL-O films in SGF (12 h incubation, 37 degrees C). When compared to PBS pH 7.4, pancreatin hardly enhanced the weight loss of PCL films and bars. In contrast, pancreatin enhanced substantially erosion of PCL-O films and bars. Unlike PCL preparations, the PCL-O preparations showed surface erosion in SIF. Pancreatin increased considerably FITC-dextran release from both PCL and PCL-O microparticles. In conclusion, the present results demonstrate the enzyme sensitivity of the novel PCL-O polymer. In addition, the results show that pancreatin present in intestinal fluid may substantially affect drug release from PCL based preparations.
Tarvainen
Tommy
T
Department of Pharmaceutics, University of Kuopio, PO Box 1627, Finland. tommy.tarvainen@uku.fi
Malin
Minna
M
Suutari
Tanja
T
Pöllänen
Mikko
M
Tuominen
Jukka
J
Seppälä
Jukka
J
Järvinen
Kristiina
K
D046911:Macromolecular Substances; D010080:Oxazoles / Q000737:chemistry / Q000493:pharmacokinetics*; D010194:Pancreatin / Q000737:chemistry / Q000493:pharmacokinetics*; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics*
D046911:Macromolecular Substances; D010080:Oxazoles; D011091:Polyesters; C016240:polycaprolactone; D010194:Pancreatin