Transcutaneous penetration

Berardesca, E., Cespa, M., Farinelli, N. et al., In vivo transcutaneous penetration of nicotinates and sensitive skin, Contact Dermatitis, 25, 35-38, 1991. 

Under production conditions, the transcutaneous penetration mechanism into the organism, i.e. through undamaged skin, follows inhalation in degree of danger. The toxicological experience of the transcutaneous effects of Cl has proved to have a local character, characterized by inflammation (skin reddening) that may be complicated by a suppurative process with deep sores. This local affect is common to the majority of Cl. 

The greater or lesser transcutaneous penetration will be directly tied to the size of the oligomer (whether dimer or tetramer) and the relative compound formed with the active substances, their thermodynamic activity, and, naturally, to the carrier used (Figure 37.6). 

Scopolamine is effective in the prophylaxis of kinetosis (motion sickness, sea sickness, see p. 330) it is well absorbed transcutaneously. Scopolamine (plblood-brain barrier faster than does atropine (pKa = 9), because at physiologic pH a larger proportion is present in the neutral, membrane-permeant form. 

The ease of application, the minimization of systemic side effects, and the increased drug penetration directly into the target region resulted in extensive clinical use of iontophoresis mainly in the transdermal field. This technique has been utilized for administration of local anesthetics [2-5], sweat chloride testing in cystic fibrosis patients by transcutaneous delivery of pilocarpine [6,7], administration of vidarabine to patients with herpes orolabialis [8], fluoride administration to patients with hypersensitive dentin [9,10], and gentamicin delivery for the management of burned ears [11],... 

Touitou et al. [50] compared penetration enhancers with liposomes. Interestingly, they found that liposomes mainly deposit the drug in the skin, and, therefore, act as an excellent reservoir, whereas the penetration enhancers increased transcutaneous transport. 

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... 

Drugs are applied topically primarily for local effects however, this route can be used to administer drugs for systemic action. Few drugs readily penetrate intact skin. The absorption of drugs that do penetrate the skin is proportional to the surface area over which they are applied and to their lipid solubility. Increased cutaneous blood flow also enhances absorption. Systemic toxicity can become evident when highly lipid-soluble substances (e.g. lipid-soluble insecticides) are absorbed through the skin. Controlled-release patches are now commonly used in human medicine for transcutaneous drug administration. 

In summary, although there is considerable evidence that parabens can penetrate into the skin, permeation and systemic availability of intact compounds are likely to be considerably reduced by transcutaneous and systemic metabolism. Furthermore, since these preservatives are present at concentrations of 0.1-0.2 percent w/w in topical pharmaceutical formulations, in-use dermal exposure to these compounds will be relatively low. In the cosmetic industry, there is a trend toward preservative-free and self-preserving formulations (Kabara and Orth 1997). However, before starting down this road, the pharmaceutical formulator must consider the potential implications on the efficacy and safety of the product. 

In addition to gastrointestinal absorption, nickel may also enter the body by inhalation, transcutaneous absorption, and parenteral administration. In humans, approximately 35% of inhaled nickel is absorbed from the respiratory tract the remainder is carried up the tracheobronchial mucociliary escalator and either swallowed or expectorated (Bennett 1984, Grandjean 1984, Sunderman 1986b). In penetration through the epidermis, nickel may be bound to urocanic acid and histidine, which occur in human sweat (Mali etal. 1964). Hostynek etal. 

Naturally, the different activities the different CN compounds have is strictly dependent not only on the different ingredients used, but also on the different emulsions, micellar or lamellar, micro- and nano-structured realized. Depending on all these parameters, it is possible to obtain a transcutaneous, transdermal, or transfollicular penetration. 

Jet injectors deliver insulin transcutaneously by an air-jet mechanism. The insulin solution or suspension is forced at high pressure through a fine nozzle, penetrates the skin without a needle, and creates a multitude of small depots. The dispersion of insulin deposited in the tissue explains the more rapid absorption of both rapid- and retarded-acting preparations (Taylor et al, 1981 Malone eta/., 1986 Houtzagerse/a/., 1988). Jet injection seems to affect the action profile of NPH insulin more markedly than that of the Lente t e insulins (Houtzagers et al, 1988). These devices are not painless and, in a European study, not well accepted by patients irrespective of the presence or absence of needle phobia (Houtzagers etal, 1988). However, in a more recent American study, the majority of patients preferred to take insulin by jet injector compared to needle injection (Denne et al, 1992). Jet injection has been found to be associated with a diminished antibody... 

Fig. 1 Schematic representation of a transcutaneous blood gas measurement. Both blood gases (CO2 and O2) diffuse through the skin of the patient and penetrate into the sensor...

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