title: Evaluation of intratympanic formulations for inner ear delivery: methodology and sustained release formulation testing.
abstract: A convenient and efficient in vitro diffusion cell method to evaluate formulations for inner ear delivery via the intratympanic route is currently not available. The existing in vitro diffusion cell systems commonly used to evaluate drug formulations do not resemble the physical dimensions of the middle ear and round window membrane. The objectives of this study were to examine a modified in vitro diffusion cell system of a small diffusion area for studying sustained release formulations in inner ear drug delivery and to identify a formulation for sustained drug delivery to the inner ear. Four formulations and a control were examined in this study using cidofovir as the model drug. Drug release from the formulations in the modified diffusion cell system was slower than that in the conventional diffusion cell system due to the decrease in the diffusion surface area of the modified diffusion cell system. The modified diffusion cell system was able to show different drug release behaviors among the formulations and allowed formulation evaluation better than the conventional diffusion cell system. Among the formulations investigated, poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) triblock copolymer systems provided the longest sustained drug delivery, probably due to their rigid gel structures and/or polymer-to-cidofovir interactions.
authors: Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati , Cincinnati, OH , USA.
authors: Hongzhuo
authors: H
authors: Liu
authors: Liang
authors: L
authors: Feng
authors: Gaurav
authors: G
authors: Tolia
authors: Mark R
authors: MR
authors: Liddell
authors: Jinsong
authors: J
authors: Hao
authors: S Kevin
authors: SK
authors: Li
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D000077404:Cidofovir; D003198:Computer Simulation; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D007758:Ear, Inner / Q000187:drug effects / Q000378:metabolism*; D004432:Ear, Middle / Q000187:drug effects / Q000378:metabolism*; D008567:Membranes, Artificial; D008954:Models, Biological; D063065:Organophosphonates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008567:Membranes, Artificial; D063065:Organophosphonates; C528571:poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid); D011098:Polyglactin 910; D011092:Polyethylene Glycols; D003596:Cytosine; D000077404:Cidofovir
keywords: Drug release; inner ear delivery; intratympanic formulation; methodology; temperature responsive gel
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