Transport across skin

II. VESICLES AFFECT DRUG TRANSPORT ACROSS SKIN A. Vesicles Affect Skin Penetration In Vitro... 

Figure 1. Typical results of 8 -estradiol transport across skin (A) saline in donor and receiver compartment. Donor compartment solution saturated with non-radiolabeled 3-estradiol. (O) saline in donor and in receiver compartments, only radiolabeled 8 -estradiol in donor compartment. ( ) ethanol in donor and in receiver compartments. Donor compartment solution saturated with non-radiolabeled 3-estradiol. ( ) ethanol in donor and receiver compartments, only radiolabeled 3-estradiol in donor compartment. Cj was 53,000 DPM/3pl in these experiments.

Finally, an example of what is not included in this contribution is, for instance, the use of scaiming electrochemical microscopy (SECM) for imaging pathways of molecular transport across skin tissues. Another topic not included, but one that has been often discussed in the literature, is the topic of electrochemical sensors in medical devices. 

Investigations of molecular transport across skin using SECM were first performed by Scott et al. to identify regions of localized transport (7). Figure... 

The majority of RDC studies have concentrated on the measurement of solute transfer resistances, in particular, focusing on their relevance as model systems for drug transfer across skin [14,39-41]. In these studies, isopropyl myristate is commonly used as a solvent, since it is considered to serve as a model compound for skin lipids. However, it has since been reported that the true interfacial kinetics cannot be resolved with the RDC due to the severe mass transport limitations inherent in the technique [15]. The RDC has also been used to study more complicated interfacial processes such as kinetics in a microemulsion system [42], where one of the compartments contains an emulsion. 

The elimination rate of a compound (directly or by biotransformation) from an organism determines the extent of the bioconcentration and depends both on the chemical and the organism. Direct elimination includes transport across the skin or respiratory surfaces, secretion in gall bladder bile, and excretion from the kidney in urine. Other processes are moulting (for arthropods), egg deposition (fish, invertebrates) and transfer to offspring or via lactation (in mammals), which are more specific and not usually contemplated in bioconcentration determination. 

FIGURE 13.3 The cumulative amount of ketorolac as a function of time from elastic and rigid vesicle formulations across human skin in vitro. Elastic vesicles were clearly more effective as compared with rigid vesicles in the enhancement of ketorolac transport across the skin. The cumulative amounts found after 1 and 4 h of elastic vesicle treatment (corresponding to the time periods chosen for this study), however, were still very low. (Reproduced from Honeywell-Nguyen, P.L. et al., J. Invest. Dermatol., 123, 902, 2004. With permission from Blackwell Publishing.)... 

Over the last 20 years, the mechanisms of iontophoretic drug transport have been elucidated. In the process, several models have been developed which (a) describe drug transport across the skin under the influence of an electric field, (b) permit drug candidates to be selected rationally, and (c) optimize iontophoretic conditions and formulations. In the first part of this chapter, the main contributions of these models to the field are summarized, and... 

Transdermal iontophoresis involves the application of an electric field across the skin to facilitate (primarily) ionic transport across the membrane. Iontophoresis, it is important to point out, is differentiated from electroporation [14], another electrical approach to enhance transdermal transport, by the low fields employed. Whereas iontophoresis has achieved commercialization, there is (to our knowledge) no active development in progress of a transdermal delivery system employing electroporation. 

Sims, S.M., W.I. Higuchi, and Y. Srinivasan. 1992. Skin alteration and convective solvent flow effects during iontophoresis II. Monovalent anion and cation transport across human skin. Pharm Res 9 1402. 

Masada, T., et al. 1989. Examination of iontophoretic transport of ionic drugs across skin Baseline studies with the four-electrode system. Int J Pharm 49 57. 

Guy, R.H., M.B. Delgado-Charro, and Y.N. Kalia. 2001. Iontophoretic transport across the skin. Skin Pharmacol Appl Skin Physiol 14 (Suppl. 1) 35. 

Mudry, B., R.H. Guy, and M.B. Delgado-Charro. 2005. Rational optimization of iontophoretic transport across the skin. In 32th Annual meeting exposition of the controlled release of bioactive materials. Miami, USA. 

Weaver, J.C., T.E. Vaughan, and Y. Chizmadzhev. 1999. Theory of electrical creation of pathways across skin transport barriers. Adv Drug Deliv Rev 35 21. 

Chen, T., R. Langer, and J.C. Weaver. 1998. Skin electroporation causes molecular transport across the stratum corneum through localised regions. J Investig Dermatol Symp Proc 3 159. 

A permeation enhancer can be defined as a compound that alters the skin barrier function so that a desired drug can permeate at a faster rate. Dozens of enhancers are patented each year, and several books have been written summarizing the work and proposing mechanisms of enhancement.70-72 The permeation enhancers may be classified simply as polar and nonpolar ones. They can be used individually or in combination, such as binary mixtures. For several drugs, the flux across skin was observed to be linear with that of the most widely used enhancer, ethanol.73-75 Another polar enhancer, isopropanol, facilitated ion association of charged molecules and enhanced the transport of both neutral and ionic species across the stratum corneum.76 77 While polar enhancers traverse the skin, nonpolar enhancers are largely retained in the stratum corneum both aspects make the combination a superior enhancer to the individual enhancers.78... 

Molecular size greatly affects transport across cellular membranes. As molecular size increases, transport across membranes decreases, because increases in molecular size will increase "frictional resistance" and decrease the diffusivity through the cell membrane. Since molecular size is generally directly proportional to molecular mass, and molecular mass is easily calculated molecular mass is often used as a descriptor of molecular size. Hence, as a general rule, the lower the molecular mass, the smaller are the molecules composing the substance, and the more easily the substance can cross membranes and be absorbed from the gastrointestinal tract, lung, and skin. 

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