Response surface methodology to investigate the iontophoretic delivery of tacrine hydrochloride.
OBJECTIVE
The objective of this work was to apply response surface approach to investigate the main and interaction effects of delivery parameters for iontophoretic delivery of tacrine HCl in vitro.


METHODS
Iontophoresis was used to deliver tacrine HCl across rat skin. Experiments were performed according to Box-Behnken design to evaluate effects of drug concentration (X1), current density (X2), and donor buffer molarity (X3) on cumulative drug delivered in 24 h (Y1), 6 h (Y2), iontophoretic flux (Y3), and post-iontophoretic flux (Y4).


RESULTS
Mathematical model for Y1 was Y1 = 0.653 + 0.163 * X1 + 0.456 * X2 - 0.156 * X3 + 0.190 * X1X2 + 0.139* X3X3. Response surface plot indicated that at low level of X2 (0.1mA/cm2), X1 had little effect on Y1. However, at high level of X2 (0.5 mA/cm2), Y1 significantly increased from 0.75 mg/cm2 to 1.46 mg/cm2 when X1 increased from 1% to 9%. Regression equations predicted responses for Y1 to Y4, for optimal formulation, which were in reasonably good agreement with experimental values.


CONCLUSIONS
Experimental design methodology revealed an interaction between drug concentration and current density, which would have been difficult to predict from one factor at a time classic experimental approach.
Upasani
Rashmi S
RS
Department of Pharmaceutical Sciences, School of Pharmacy, Mercer University, Atlanta, Georgia 30341, USA.
Banga
Ajay K
AK
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods*; D051381:Rats; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013499:Surface Properties; D013619:Tacrine / Q000008:administration & dosage* / Q000493:pharmacokinetics
D013619:Tacrine