Comparing different salt forms of rotigotine to improve transdermal iontophoretic delivery.
The transdermal delivery of a new salt form of the dopamine agonist rotigotine, rotigotine.H(3)PO(4) is presented and compared to rotigotine.HCl. A comparison was made on the level of solubility, passive and iontophoretic delivery. Different aspects of the delivery were investigated: delivery efficiency, maximum flux, donor pH, electro-osmotic contribution and transport number. Changing the salt form from rotigotine.HCl to rotigotine.H(3)PO(4) increases significantly the solubility and rules out the influence of NaCl on the solubility by the absence of the common-ion effect. At low donor concentration, no difference in transdermal delivery was observed between the salt forms. Due to an increase in the maximum solubility of rotigotine.H(3)PO(4), a 170% increase in maximum flux, compared to rotigotine.HCl, was achieved. A balance between solubility and delivery efficiency can be obtained by choosing the correct donor pH between 5 and 6. A slight increase in electro-osmotic contribution and transport number was observed. Using the parameters, determined by modeling the in vitro transport, in vivo simulations revealed that with iontophoresis therapeutic levels can be achieved with a rapid onset time and be maintained in a controlled manner by adjusting the current density.
Ackaert
O W
OW
Division of Drug Delivery Technology, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden, The Netherlands.
Eikelenboom
J
J
Wolff
H M
HM
Bouwstra
J A
JA
D000279:Administration, Cutaneous; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003198:Computer Simulation; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000737:chemistry; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods*; D017711:Nonlinear Dynamics; D012492:Salts / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage* / Q000737:chemistry; D013876:Thiophenes / Q000008:administration & dosage* / Q000737:chemistry
D018491:Dopamine Agonists; D012492:Salts; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C047508:rotigotine