title: Pilocarpine permeability across ocular tissues and cell cultures: influence of formulation parameters.
abstract: In vitro permeation studies of drugs across biological barriers are promising tools for estimating the quality and quantity of drug transport in vivo. The objective of this work was to compare the permeability of the hydrophilic model drug pilocarpine-HCl (P-HCl) through different ocular tissues and cell cultures: isolated pig cornea (PCr) and sclera (PSc), rabbit conjunctiva (RCo), and rabbit conjunctival (RCoEC) or corneal epithelial cell culture (RCrEC). Furthermore, the study included investigations about the influence of the excipients benzalkonium chloride (BAC) and ethylene diamine tetra acetic acid disodium salt (EDTA) on the permeability of the small drug. In general, BAC caused a facilitated drug transport, while EDTA hardly influenced the P-HCl concentration on the acceptor side, except for RCoEC. Additionally, the impact of variation in buffer solution pH and tonicity on drug transport in both cell cultures was tested. The higher the tonicity of the buffer solution (80, 300, and 600 mOsm/kg) the lower the permeability coefficient (P(eff)). At different pH values (6.4, 7.4, and 8.4) the P(eff) showed a directly proportional demeanor. In summary, a good correlation between the isolated tissues and cell cultures with regard to P-HCl transport could be observed.
authors.affiliation: Humboldt University of Berlin, Institute of Pharmacy, Department of Pharmaceutical Technology, Berlin, Germany. tinischolz@gmx.de
authors.forename: Martina
authors.initials: M
authors.lastname: Scholz
authors.forename: Joan-En Chang
authors.initials: JE
authors.lastname: Lin
authors.forename: Vincent H L
authors.initials: VH
authors.lastname: Lee
authors.forename: Sigrid
authors.initials: S
authors.lastname: Keipert
mesh_terms: D000818:Animals; D002021:Buffers; D002478:Cells, Cultured; D003228:Conjunctiva / Q000166:cytology / Q000378:metabolism*; D003315:Cornea / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005079:Excipients / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008297:Male; D018721:Muscarinic Agonists / Q000493:pharmacokinetics*; D010539:Permeability / Q000187:drug effects; D010862:Pilocarpine / Q000493:pharmacokinetics*; D011817:Rabbits; D012590:Sclera / Q000378:metabolism*; D013552:Swine
chemical_list: D002021:Buffers; D005079:Excipients; D018721:Muscarinic Agonists; D010862:Pilocarpine