Physical transdermal enhancers

For example, the permeability coefficients of intact stratum corneum for lipophilic compounds such as corticosterone are in the order of 2 x lO cm/sec in an aqueous system. The aqueous solubility of corticosterone is approximately 0.3mg/mL.f A simple calculation using Eqs. (1) and (2) show why only potent drug of a required dose less than 1 mg per day can utilize the transdermal route via passive delivery. Physical and chemical transdermal enhancers are required for most drugs. Table 1 provides a list of transdermal enhancement methods and companies involved in the development of technologies related to these methods. The readers are encouraged to view the company websites listed in the table, but caution must be taken because the information and claims provided in a company website are subjective and not peer-reviewed. 

The use of skin permeation enhancers in combination for synergistic effects has been studied in the transdermal literature (70). Such synergistic methods can be grouped in three categories (i) combination of two physical methods, e.g., ultrasound and iontophoresis (71-75) (ii) combination of a physical method with a chemical enhancer, e.g., use of ultrasound with sodium lauryl sulfate or isopropyl myristate (76-80) and (iii) combination of two chemicals, e.g., terpenes and propylene glycol (46,81-88). Numerous studies have been published on using combination of two physical methods or use of a physical method in conjunction with a chemical enhancer. Use of a physical method, by itself or in combination with another physical method, increases application cost for delivery purposes as mentioned before. In addition, there are unexplored safety and membrane recovery issues associated with these methods. A few reports have also been published on the use of a mixture of chemical enhancers for enhancing transdermal delivery. Typically, such studies use... 

Asbill C, El-Kattan A, Michniak B. Enhancement of transdermal drug delivery chemical and physical approaches. Crit Rev Ther Drug Carrier Syst 2000 17 621-658. 

Fang J, Hwang T, Huang Y, Tsai Y. Transdermal iontophoresis of sodium nonivamide acetate—V. Combined effect of physical enhancement methods. Int J Pharm 2002 235 95-105. 

The remarkable resistance of the SC intercellular lipid network to the passive penetration of therapeutic agents has intensified the search for devices, chemical and physical, with the ability to perturb this lipid environment. Of the many physical techniques investigated, iontophoresis (or electrically enhanced transdermal transport) has become an important focal point [160-162]. Unparalleled in its ability to deliver (noninvasively) ionized drugs across the skin, its modus operandi appears to be largely dependent on transcutaneous ion-conducting pathways (which may be paracellular), rather than a function of direct interaction with the lipid infrastructure [163]. Nevertheless, the effect of the applied current on the lipid (and protein) domains is a matter of interest with respect to both safety considerations (i.e., does the applied current induce stmctural alterations ) and mechanistic insight. ATR-FTIR has been used in a number of studies to discern the effect of iontophoresis on SC lipid and protein structures, both in vivo and in vitro. In separate studies, human SC was examined in vivo following the delivery of current at 0.1-0.2 mA/cm for 30... 

Cross SE and Roberts MS. Physical enhancement of transdermal drug apphcation Is delivery technology keeping up with pharmaceutical development Curr. Drug Deliv. 2004 1 81-92. 

To further illustrate the mechanisms of chemically and physically enhanced transdermal transport, a transdermal transport model will be discussed here. Generally, the permeability of the stratum corneum can be divided into parallel lipoidal and pore pathway... 

Murthy, S.N. and Hiremath, R.R. (2001) Physical and chemical permeation enhancers in transdermal delivery of terbutaline sulphate . AAPS PharmSciTech. 2, 1-5. 

Cohen-Avrahami M, Shames Al, Ottaviani ME, Aserin A, Garti N. HfV-TAT Enhances the transdermal delivery of NSAID drugs from liquid crystalline mesophases. The Journal of Physical Chemistry B. 2014 118(23) 6277-6287. 

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