title: Effects of drug solubility, state and loading on controlled release in bicomponent electrospun fibers.
abstract: Bicomponent fibers of two semi-crystalline (co)polymers, poly(varepsilon-caprolactone), and poly(oxyethylene-b-oxypropylene-b-oxyethylene), were obtained by electrospinning. Acetazolamide and timolol maleate were loaded in the fibers in different concentrations (below and above the drug solubility limit in polymer) in order to determine the effect of drug solubility in polymer, drug state, drug loading and fiber composition on fiber morphology, drug distribution and release kinetics. The high loadings fibers (with drug in crystalline form) showed higher burst and faster release than low drug content fibers, indicating the release was more sustained when the drug was encapsulated inside the fibers, in amorphous form. Moreover, timolol maleate was released faster than acetazolamide, indicating that drug solubility in polymer influences the partition of drug between polymer and elution medium, while fiber composition also controlled drug release. At low loadings, total release was not achieved (cumulative release percentages smaller than 100%), suggesting that drug remained trapped in the fibers. The modeling of release data implied a three stage release mechanism: a dissolution stage, a desorption and subsequent diffusion through water-filled pores, followed by polymer degradation control.
authors.affiliation: Department of Chemical Engineering, University of Coimbra, Pólo II, Pinhal de Marrocos, 3030-290 Coimbra, Portugal.
authors.forename: Mădălina V
authors.initials: MV
authors.lastname: Natu
authors.forename: Hermínio C
authors.initials: HC
authors.lastname: de Sousa
authors.forename: M H
authors.initials: MH
authors.lastname: Gil
mesh_terms: D000086:Acetazolamide / Q000737:chemistry / Q000493:pharmacokinetics*; D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000493:pharmacokinetics*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004058:Diffusion; D004304:Dosage Forms; D008962:Models, Theoretical; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013999:Timolol / Q000737:chemistry / Q000493:pharmacokinetics*; D014867:Water / Q000737:chemistry
chemical_list: D000319:Adrenergic beta-Antagonists; D002257:Carbonic Anhydrase Inhibitors; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D011108:Polymers; D014867:Water; D013999:Timolol; D000086:Acetazolamide