title: A new hydrogel for the extended and complete prednisolone release in the GI tract.
abstract: The issue of incomplete release of poorly soluble drugs from sustained-release oral formulations is addressed using prednisolone (PDS) as the model drug and a novel highly swelling hydrogel as the rate-controlling material. The hydrogel was formed by heating N-carboxymethylchitosan (CMC) to 80 degrees C for 24 h. Swelling, alkalimetry, FTIR, DSC, and solid-state NMR studies showed that the treatment produced physical crosslinking, i.e., polymer chain entanglement. A controlled-release system was prepared by coating an inert compacted support of ethylcellulose (50 mg; diameter, 6 mm) with a CMC layer containing dispersed PDS powder (10-50 microm). The system was heated to crosslink the CMC coating, then drug release to simulated GI fluids was studied in vitro. The drug release pattern and term were modulated via the layer mass (LM) (10 or 14 mg cm(-2)) and/or the drug-polymer wt ratio (D/P) (1:5 or 2:5). The rate parameter, K, and the time exponent, n, of the Peppas equation were: K=26.6+/-0.3 h(-n), n = 0.78+/-0.02 (LM, 10 mg cm(-2); D/P, 1:5); K = 24.7+/-0.7 h(-n), n = 0.56+/-0.02 (LM, 14 mg cm(-2); D/P, 1:5); K = 20.7+/-0.3 h(-n), n = 0.76+/-0.01 (LM, 10 mg cm(-2); D/P, 2:5). Hydrogel swelling was faster than drug release. This was controlled, in a first stage, by drug dissolution-diffusion in the swollen gel, and subsequently, by diffusion. The drug release rate was unaffected by the GI pH variations, and slightly affected by the environmental hydrodynamics. The system promises an extended and complete release of poorly soluble drugs in the GI tract.
authors.affiliation: Department of Bioorganic Chemistry and Biopharmaceutics, University of Pisa, Via Bonanno 33, 56126 Pisa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Di Colo
authors.forename: A
authors.initials: A
authors.lastname: Baggiani
authors.forename: Y
authors.initials: Y
authors.lastname: Zambito
authors.forename: G
authors.initials: G
authors.lastname: Mollica
authors.forename: M
authors.initials: M
authors.lastname: Geppi
authors.forename: M F
authors.initials: MF
authors.lastname: Serafini
mesh_terms: D048271:Chitosan / Q000737:chemistry; D003692:Delayed-Action Preparations; D004058:Diffusion; D041981:Gastrointestinal Tract / Q000737:chemistry / Q000378:metabolism; D020100:Hydrogels / Q000737:chemistry*; D066298:In Vitro Techniques; D007700:Kinetics; D008954:Models, Biological; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D011239:Prednisolone / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D020100:Hydrogels; D011108:Polymers; D014867:Water; C068302:N-(carboxymethyl)chitosan; D048271:Chitosan; D011239:Prednisolone