Journal
COMPUTERS & CHEMICAL ENGINEERING
Volume 35, Issue 6, Pages 1152-1163Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.compchemeng.2011.01.006
Keywords
Transdermal; Nonlinear pharmacokinetics; Mathematical model; Heat; Optimization; Process design
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Process modeling and design concepts were implemented to aid in the manufacturing of heat-enhanced transdermal drug-delivery systems. The simulated prototype consists of a corticosterone-loaded polymer patch applied to the skin and connected to a heating device in which an exothermic reaction occurs. To achieve a desired transdermal flux of 1.2 x 10(-5) mg/cm(2) h, this contribution focuses on the influences of the (1) initial reaction rate (-r(A0)), (2) mass of filler material in the device (m), (3) initial concentration (C-0) of medicament in the patch and (4) overall heat transfer coefficient (U). A regression technique yielded the following results: -r(A0) = 3.000 x 10(-2) kg/m(3) s, m = 1.251 x 10(-8) kg, U = 6.124 x 10 J/m(2) Ks and C-0 = 1.966 x 10(-1) kg/m(3). When m was fixed at 12.5 g, the optimum design required the following specifications: r(A0) = 2.765 x 10(-2) kg/m(3) s, U = 1.402 x 103 J/m(2) Ks and C-0 = 1.941 x 10(-1) kg/m(3). The priority (S-i) of the input factors (i) in reaching the target delivery rate is: S-C0 > S-rA0 > S-m > S-U. (C) 2011 Elsevier Ltd. All rights reserved.
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