title: Evaluation of a mucoadhesive tablet for ocular use.
abstract: The present study investigates the use of a polymer mixture containing Carbopol 974P and drum dried waxy maize starch to obtain prolonged drug release to the anterior eye segment. Two dosage forms with this composition are compared: a hydrated polymer dispersion and a minitablet. A model fluorescent tracer is used to study the ocular release and diffusion from the two dosage forms in humans. To evaluate the prolongation in the cornea/tearfilm compartment, the Apparent Fluorescein TurnOver (%/min) is calculated. The parameters Cmax, tmax, and C9h are used to characterize the pharmacokinetics of Na-fluorescein in the anterior chamber. Furthermore, the swelling behavior of the minitablet is evaluated macroscopically, while the degree of interaction with mucin is characterized by rheological measurements. Calculation of an acceptability score and a slug irritation potential is performed to evaluate user acceptability. In contrast to the hydrated dispersion, the minitablet significantly decreases the Apparent Fluorescein TurnOver (%/min) (P<0.05) and increases the apparent fluorescence in the anterior chamber 9 h after application of the preparation. Rheological data demonstrate the presence of elastic interactions between the polymer and mucin. The dry core of the minitablet becomes fully hydrated after approximately 2 h and is subsequently transformed into a highly concentrated gel. The acceptability of the minitablet is comparable to that of the polymer dispersion. Prolonging the release of Na-fluorescein to the anterior eye segment is only feasible with the dry preparation.
authors.affiliation: Laboratory of Pharmaceutical Technology and Biopharmacy, Department of Pharmaceutical Sciences, Antwerp University, Universiteitsplein 1, B-2610, Antwerp, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Ceulemans
authors.forename: A
authors.initials: A
authors.lastname: Vermeire
authors.forename: E
authors.initials: E
authors.lastname: Adriaens
authors.forename: J P
authors.initials: JP
authors.lastname: Remon
authors.forename: A
authors.initials: A
authors.lastname: Ludwig
mesh_terms: D000179:Acrylates / Q000008:administration & dosage / Q000493:pharmacokinetics; D000269:Adhesives / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects / Q000378:metabolism*; D004341:Drug Evaluation / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008974:Mollusca; D009092:Mucous Membrane / Q000378:metabolism; D011108:Polymers / Q000008:administration & dosage / Q000493:pharmacokinetics; D013607:Tablets / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000179:Acrylates; D000269:Adhesives; D011108:Polymers; D013607:Tablets; C117167:carbopol 974P NF