Transdermal drug delivery absorption

Nevertheless, there are reports on enhancement of ocular drug absorption by bile salts [33], surfactants [200], and chelators [149], Newton et al. [35] demonstrated that Azone, an enhancer widely tested in transdermal drug delivery [201], increased the ocular absorption of cyclosporine, an immunosuppressant, by a factor of 3, thereby prolonging the survival of a corneal allograft. In 1986, Lee et al. [34] reported that 10 pg/mL cytochalasin B, an agent capable of condensing the actin microfilaments, increased the aqueous humor and iris-ciliary body concentrations of topically applied inulin (5 kDa) by about 70% and 700%, respectively, in the albino rabbit. 

Ho CK (2004) Probabilistic modeling of peracutaneous absorption for risk-based exposure assessments and transdermal drug delivery. Statistical Methodology 1 47-69... 

Transdermal drug delivery is an attractive route of drug administration and will continue to proliferate in the following years. In the developmental stages it is important to have predictive models and to be able to identify suitable drug candidates. Although still in its infancy, the approach described above can be used predictively and as the mechanisms involved in percutaneous absorption are better understood and quantified the model can be refined accordingly. 

Because of the large surface area of the skin and its bypass of the liver as a first pass step in metabolism, many drug delivery systems have been developed that control the rate of drug delivery to the skin for subsequent absorption. Effective transdermal drug delivery systems of this type deliver uniform quantities of drug to the skin over a period of time. Technically, transdermal drug delivery systems may be classified into monolithic and membrane-controlled systems (9). 

These linear kinetic models and diffusion models of skin absorption kinetics have a number of features in common they are subject to similar constraints and have a similar theoretical basis. The kinetic models, however, are more versatile and are potentially powerful predictive tools used to simulate various aspects of percutaneous absorption. Techniques for simulating multiple-dose behavior evaporation, cutaneous metabolism, microbial degradation, and other surface-loss processes dermal risk assessment transdermal drug delivery and vehicle effects have all been described. Recently, more sophisticated approaches involving physiologically relevant perfusion-limited models for simulating skin absorption pharmacokinetics have been described. These advanced models provide the conceptual framework from which experiments may be designed to simultaneously assess the role of the cutaneous vasculature and cutaneous metabolism in percutaneous absorption. 

While the infinite dose technique has been invaluable in the determination of important skin permeability parameters such as dermal penetration coefficients and in the development of transdermal drug delivery concepts, to mimic in vivo conditions, the so-called finite dose technique was developed. This is essentially a modification of the traditional steady-state method. The important difference is that the skin preparation is supported over the receptor so that the epidermal surface is exposed in a manner that mimics the real-life exposure scenario, and the compound of interest is applied to the surface of the skin in a manner also similar to exposure in vivo. Although the results of such studies may give valuable information about the absorption of materials under specific exposure conditions, they are generally not amenable to extrapolation to other exposures since no invariant skin properties such as penetration coefficients can be readily calculated. 

A transdermal therapeutic system is a rate-controlled drug delivery system which, applied to the surface of the skin, continuously releases the drug at a rate that will provide a desired steady-state plasma concentration for a specified duration. A candidate drug must possess high activity (i.e. be effective at low plasma concentrations) and efficiently penetrate the stratum comeum-, percutaneous absorption must be reliably consistent. Based on technological design there are four types of rate-controlled transdermal drug delivery system (Chien, 1987) ... 

For many pharmaceutical compounds administered as transdermal drug delivery systems, absorption can be assessed by determining the area under the curve (AUC) of the plasma concentration-time profile, the peak plasma flux, and time of peak flux, much as it is for determining bioavailability from oral and other routes of administration. These are classical metrics of biophar-maceutical bioequivalence studies and are extensively covered in other texts... 

Bemabei, G.F., Method and apparatus for skin absorption enhancement and transdermal drug delivery . US Pat. 7,083,580. 

Transdermal drug delivery can be used in pediatric patients (1) to avoid problems of drug absorption from the oral route and complications from the intravenous route and (2) to maximize duration of effect and minimize adverse effects of drugs. Unfortunately, the commercially available transdermal dosage forms (e.g., clonidine and scopolamine) are not intended for pediatric patients these would deliver doses much higher than those needed for infants and children. 

Vecchia, B.E. and Bunge, A.L. (2002b). Skin absorption databases and predictive equations, in J. Hadgraft and Guy, RH. (eds.), Transdermal Drug Delivery Systems, New York Dekker, pp. 57-141. 

There is also increasing interest in the per-acyl-CDs. All acetylated CDs from per-acetyl to per-octanoyl esters were studied partly as retard drug carriers (to retard the drug release for absorption from its pharmaceutical formulation). partly as bioadhesive, film-forming substances to be used in transdermal drug delivery systems. 

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