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Rheology of drugs for topical and transdermal delivery

Walicka A., Falicki J., Iwanowska-Chomiak B.

International Journal of Applied Mechanics and Engineering

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2019

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Vol. 24, no. 1

179--198

EN

Skin drug delivery systems are a constant source of interest because of the benefits that they offer to overcome many drawbacks associated with other modes of drug delivery (i.e. oral, intravenous, etc.). Because of the impermeable nature of the skin, designing a suitable drug delivery vehicle that penetrates the skin barrier is challenging. Skin drug delivery can be subdivided into topical and transdermal (Fig.1). In a topical administration the drug is intended to act at skin level, this is indicated for the treatment of skin diseases. The aim of transdermal administration is getting a systemic release and in this case the skin represents a barrier not a target. The availability of drugs or other active substances through the skin depends basically on two consecutive steps: the release of these drugs or substances from vehicle or carrier and their subsequent permeation through the skin. Hence, studies on the specific properties of vehicles or carriers, such as their rheological behaviours, are of great interest in the field of pharmaceutical products. The objective of the present study is to systematically characterize a nonlinear rheological behaviour and flow properties of drugs and drug carriers into topical and transdermal administration. To this aim, one- and threedimensional rheological models are presented, which may be used to describe drug release through the skin and through the extracellular and interstitial matrix structures. Finally, the rheological measurements of some commercial creams and ointments were made.

2

Mass transport through interstitial structures

Iwanowska-Chomiak B., Walicka A.

International Journal of Applied Mechanics and Engineering

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2019

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Vol. 24, no. 4

66--91

EN

Interstitial space, also called interstitum, separating the vital organs of a human body, is the primary source of lymph and is a major fluid compartment in the body. Interstitial space (IS) is filled out by thick collagen (CL) bundles which form lattices represented by a network of capillaries. This network has the structure similar to a sponge porous matrix (SPM) with pores-capillaries of variable cross-section. To analyse the mass transport of interstitial fluids (IFs) through the porous matrix it is assumed that the SPM is composed of an irregular system of pores which may be modelled as a fractal porous matrix. The interstitial fluids can be either bio-suspensions or bio-solutions and therefore they have to be modelled as non-Newtonian fluids. Analysing the fluid flow through the porous matrix it is assumed that the SPM is modelled as capillary tubes of variable radii. Introducing a hindrance factor allowed us to consider the porous matrix as a system of fractal capillaries but of constant radii. Classical and fractal expressions for the flow rate, velocity and permeability are derived based on the physical properties of the capillary model of interstitial structures. Each parameter in the proposed expressions does not contain any empirical constant and has a clear physical meaning, and the proposed fractals models relate the flow properties of the fluids under consideration with the structural parameters of interstitium as a porous medium.

3

Fractal model of transdermal drug delivery

Walicka A., Iwanowska-Chomiak B.

International Journal of Applied Mechanics and Engineering

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2018

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Vol. 23, no. 4

989--1004

EN

Skin, separating the vital organs of a human body, is a desirable route for drug delivery. However, the intact skin is normally permeable only for drug molecules with a low molecular weight. The stratum corneum (SC), being the outermost layer of the skin and the epidermis being the second – more permeable – layer of the skin, play an essential function in transdermal drug delivery. Physical and chemical methods of skin poration are used to enhance transdermal drug delivery. Each poration leads to an irregular system of pores which are connected with a system of micro-capillaries passing through the epidermis. Both the systems by their irregularity form a fractal porous matrix. Drugs administrated by this matrix can be either suspensions and solutions or creams and gels, therefore they have to be modelled as non-Newtonian fluids. To analyse the fluid flow through the porous matrix the model of the epidermis is assumed as gobbet-andmortar with the tortuous mortar of variable thickness and after transition from the mortar to the tube one considered classical and fractal capillary flows of selected non-Newtonian fluids. Fractal expressions for the flow rate, velocity and permeability of fluids flow in a porous matrix are derived based on the fractal properties of the epidermis and capillary model. Each parameter in the proposed expressions does not contain any empirical constant and has a clear physical meaning and the proposed fractal models relate the flow properties of considered fluids with the structural parameters of the epidermis as a porous medium. The presented analytical expressions will help understand some of the physical principles of transdermal drug delivery.

4

Drug diffusion transport through human skin

Walicka A., Iwanowska-Chomiak B.

International Journal of Applied Mechanics and Engineering

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2018

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Vol. 23, no. 4

977--988

EN

The stratum corneum (SC) forms the outermost layer of the human skin and is essentially a multilamellar lipid milieu punctuated by protein-filled corneocytes that augment membrane integrity and significantly increase membrane tortuosity. The lipophilic character of the SC, coupled with its intrinsic tortuosity, ensure that it almost always provides the principal barrier to the entry of drug molecules into the organism. Drugs can be administered either as suspensions or as solutions and the formulation can range in complexity from a gel or and ointment to a multilayer transdermal path. In this paper, we discuss theoretical principles used to describe transdermal release and we show that relatively simple membrane transport models based on the appropriate solution to the Fick’s second law of diffusion can be used to explain drug release kinetics into such a complex biological membrane as the human skin. To apply the Fick’s law we introduced into our considerations a brick-and-mortar model with two factors of tortuosity. Assuming that the mortar thickness is variable we also introduced the hindrance factor allowing us to model this variability. Having the modified Fick’s equation we presented its general solution and two special cases of this solution frequently applicable in permeation experiments. It seems that the solutions presented herein better approximate the real conditions of drug delivery then these well known.