Modeling Of Drug Delivery From Erodible And Non-Erodible Laminated Planar Devices Into a Finite External Medium

Journal of Membrane Science 350 (2010) 10–18

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Journal of Membrane Science
journal homepage: www.elsevier.com/locate/memsci

Modeling of drug delivery from erodible and non-erodible laminated planar devices into a finite external medium
Ignacio M. Helbling ∗ , Juan C.D. Ibarra, Julio A. Luna, María I. Cabrera, Ricardo J.A. Grau
Laboratorio deQuímica Fina, Instituto de Desarrollo Tecnológico para la Industria Química (INTEC), Universidad Nacional del Litoral and Consejo Nacional de Investigaciones Científicas y Técnicas (UNL-CONICET), Centro Científico Tecnológico, Ruta Nacional 168, Paraje El Pozo 3000, Santa Fe, Argentina

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Analytical solutions based on the pseudo-steady state approximation(PSSA) were derived for the case of controlled dispersed-drug release from erodible and non-erodible planar matrices, through a membrane, and taking into account the existence of a diffusion boundary layer and a finite release medium. The solutions can be applied to a broad range of situations from drug release into finite or infinite medium, from erodible or non-erodible matrices, in the presence orabsence of a membrane, and in the presence or absence of a stagnant liquid layer. The prediction is accurate for the cases in which the initial drug load is higher than the drug solubility in the polymer (e.g. A/Cs ≥ 3) till the entire dispersed drug is dissolved. The dependence on the release kinetics with different parameters was simulated and provides a theoretical platform for the design ofdispersed-drug release devices. © 2009 Elsevier B.V. All rights reserved.

Article history: Received 2 October 2009 Received in revised form 2 December 2009 Accepted 4 December 2009 Available online 30 December 2009 Keywords: Mathematical modeling Dispersed drug Moving front Finite external medium Erodible device

1. Introduction In the last few decades, transdermal therapeutic systems (TTS) havebeen designed and employed to provide a controlled release of drugs through the skin to the systemic bloodstream. The first transdermal patch released scopolamine and was manufactured in 1981 [1]. The TTS may consist of matrix or reservoir systems. In matrix systems, the initial drug loading (A) is generally uniform and can be lower [2–7] or higher [6–11] than the maximum solubility in the polymer(Cs). In the cases in which A > Cs, the drug is homogeneously dispersed as discrete crystals or solid particles in a matrix environment formed by the cross-linking of linear polymer chains. The dispersed drug crystals (particles) cannot delocalize their positions in the polymeric matrix. It is assumed that the drug molecules can elute outside the matrix only by dissolution in and then by diffusionthrough the polymeric structure. Microscopically, the solid drug particles in the layer closer to the device surface are the first to elute. When this layer becomes “exhausted”, the solid drugs in the next layer begin to be depleted. There exists a drug depletion zone with a thickness S. This thickness increases with time and as more solid drugs elute out of the device, thus leading to the inwardadvancement of the interface of the dispersed drug zone/depleted drug zone, phenomenon commonly referred to as “dissolution–diffusion moving front” [9].

∗ Corresponding author. Tel.: +54 342 4511597; fax: +54 342 4511597. E-mail address: ihelbling@santafe-conicet.gov.ar (I.M. Helbling). 0376-7388/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.memsci.2009.12.007In the last five decades, there have been numerous attempts to model the kinetics of the dispersed-drug release from planar matrices. Higuchi was the first to propose a pseudo-steady state approximation (PSSA) to derive an analytical solution for the slab under “sink condition” [12]. Later, Paul and McSpadden achieved an exact solution for slabs under “sink condition” [13]. Lee developed an...