title: Dissolution of anecortave acetate in a cylindrical flow cell: re-evaluation of convective diffusion/drug dissolution for sparingly soluble drugs.
abstract: Steady-state drug release rates were measured from a model cylindrical implant, comprised mainly of the sparingly soluble drug anecortave acetate, suspended as an obstacle in a cylindrical flow cell. Dissolution medium was delivered at a steady, slow flow rate (0.05-0.7 mLs/min) using an HPLC pump, and samples from the outflow were analyzed by direct injection onto an HPLC column. Release rates were determined as a function of flow rate for three different implant orientations--vertical, elevated to the center of the dissolution cell; horizontal, elevated; and horizontal, resting directly upon the flat porous inlet frit. Release rates were ranked as follows: horizontal, floor >> horizontal, elevated>vertical, elevated. The steady, laminar flow enabled use of the finite element method (FEM) to simulate the dissolution process using convective diffusion/drug dissolution theory. Simulations predicted the absolute magnitude of the release rate to within < 10% for all situations, and predicted the power law exponent of the dependence of release rate on flow rate with great accuracy. The current method is more general than compendial methods that provide a dissolving surface that is uniformly accessible to the dissolution medium, or a shear rate that is uniform across the entire dissolving surface. The current approach may be utilized to provide estimates of dissolution rates for any geometry and set of hydrodynamic conditions that can be numerically calculated.
authors.affiliation: Drug Delivery, Alcon Research, Ltd, Fort Worth, TX 76134, USA. paul.missel@alconlabs.com
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Missel
authors.forename: L E
authors.initials: LE
authors.lastname: Stevens
authors.forename: J W
authors.initials: JW
authors.lastname: Mauger
mesh_terms: D000465:Algorithms; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004058:Diffusion; D004343:Drug Implants / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D011244:Pregnadienediols / Q000737:chemistry / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D004343:Drug Implants; D011244:Pregnadienediols; C418047:anecortave acetate