Transdermal iontophoretic delivery of methylphenidate HCl in vitro.
Methylphenidate is prescribed orally for Attention Deficit Disorder in children and adults, and for narcolepsy patients. Methylphenidate has a short plasma half-life (1-2 h) and thus needs to be frequently administered for effective therapy. Such therapy has limitations in terms of patient compliance, particularly in young children. For such reasons, the development of a transdermal dosage form of methylphenidate may be useful. This study was undertaken to evaluate the passive and electrically assisted transport (iontophoresis) of methylphenidate from aqueous methylphenidate hydrochloride solutions across excised human skin. A maximum flux of 12.0 micrograms/(cm2 h) of protonated methylphenidate was estimated from the passive transport data at pH 3.5. Iontophoresis significantly enhanced protonated methylphenidate transport as compared with passive delivery. From the present experiments, the efficiency of iontophoretic delivery of methylphenidate was approximately 700 micrograms/(mA h). Based on in vitro skin flux data, the daily dose of 15-40 mg methylphenidate can be achieved using a current density of 0.5 mA/cm2 and a minimum transport area of 2-5 cm2 for 24-h application, or an area of 4-10 cm2 for 12-h (daytime) application. From methylphenidate skin flux values, methylphenidate mobility of 2.2 x 10(-4) cm2/(V s) was estimated, which compares reasonably with its free solution mobility of 6.6 x 10(-4) cm2/(V s).
Singh
P
P
Novartis Pharmaceuticals Corporation, Suffern, NY 10901, USA.
Boniello
S
S
Liu
P
P
Dinh
S
S
D000279:Administration, Cutaneous; D001692:Biological Transport; D000697:Central Nervous System Stimulants / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003217:Conductometry; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007478:Iontophoresis; D008774:Methylphenidate / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism*; D012995:Solubility
D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate