Controlled transport of timolol maleate through artificial membranes under passive and iontophoretic conditions

D.F. Stamatialis*, H.H.M. Rolevink, G.H. Koops

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Scopus)
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The passive and iontophoretic permeability of timolol maleate (TM) through porous and dense artificial membranes was investigated in order to select the most optimal membrane for a transdermal drug delivery system. For the meso-porous membranes (pore diameter 2–50 nm), the TM permeability for passive diffusion and iontophoresis was practically the same. For the micro-porous membranes (pore diameter<2 nm), a significant transport contribution of iontophoresis was observed, which was more pronounced when higher current densities were applied. The electrical resistance of all the porous membranes was lower than the electrical resistance of human skin. For dense membranes, passive and iontophoretic TM permeability was significantly lower than for porous membranes and in most cases their electrical resistance was comparable or even higher than the resistance of human skin. For most of the membranes studied the average adsorption of TM at 37 °C was low (0.02–0.33 mg/cm2) and independent of the TM concentration. For the meso-porous mixed cellulose acetate–cellulose nitrate membrane the TM adsorption was significantly higher and increased with the TM concentration. Based on our results, the optimum membrane for an iontophoretic transdermal TM delivery system is the LFC 1 micro-porous membrane because it mainly controls the TM delivery (TM iontophoretic permeability: 0.86×10−6 cm/s), has very low electrical resistance (0.9–1.5 kΩ cm2) and the TM adsorption to it is low (0.15 mg/cm2). The therapeutic plasma TM concentration is achievable by application of this membrane in realistic sizes (5–64 cm2) and by application of current densities between 0.13 and 0.5 mA/cm2.
Original languageEnglish
Pages (from-to)335-345
JournalJournal of controlled release
Issue number3
Publication statusPublished - 2002


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