Drug delivery, membranes transdermal administration

Toxicology of the methylated derivatives has not been studied extensively. The LD50 for oral administration of dimethyl (3-cyclodextrin is >300mg/Kg and >200mg/Kg for intravenous administration in mice.65 Methylated derivatives interact with cellular membranes, extracting cholesterol and disrupting the membranes. This has limited interest in the derivatives for intravenous delivery of pharmaceuticals, but there has been some interest in use of methylated derivatives to enhance transdermal administration of drugs.66... 

Scopolamine was the first drug to be marketed as a transdermal delivery system (Transderm-Scop) to alleviate the discomfort of motion sickness. After oral administration, scopolamine has a short duration of action because of a high first-pass effect. In addition, several side-effects are associated with the peak plasma levels obtained. Transderm-Scop is a reservoir system that incorporates two types of release mechanims a rapid, short-term release of drag from the adhesive layer, superimposed on an essentially zero-order input profile metered by the microporous membrane separating the reservoir from the skin surface. The scopolamine patch is able to maintain plasma levels in the therapeutic window for extended periods of time, delivering 0.5 mg over 3 days with few of the side-effects associated with (for example) oral administration. 

In membrane diffusion systems the polymer membrane with a given pore size or pore size distribution controls the diffusion of the active substance from the drug reservoir. Dosage forms with membrane-controlled drug delivery can be coated tablets, coated granules or pellets, or so-called multiparticulate systems on which various coats are applied. One possibility for transdermal drug administration is the transdermal patch controlled with a membrane [4-7,34-39]. 

To date, Raman spectroscopy has been used for the characterization of stratum corneum, epidermal membrane and dermal tissue. Of current interest is the administration of therapeutic agents across the skin barrier (transdermal drug delivery) however, there are a number of difficulties which involve the supply, storage and use of biohazardous human material. 

Nitroglycerin (NTC) is distinguished by a high membrane penetrability and very low stability. It is the drug of choice in the treatment of angina pectoris attacks. For this purpose, it is administered as a spray, or in sublingual or buccal tablets for transmucosal delivery. The onset of action is between 1 and 3 minutes. Due to a nearly complete presystemic elimination, it is poorly suited for oral administration. Transdermal delivery (nitroglycerin patch) also avoids presystemic elimination. 

For systemic effect. Transdermal delivery systems (TDS) release drug through a rate-controlling membrane into the skin and so into the systemic circulation. Fluctuations in plasma concentration associated with other routes of administration are largely avoided, as is first-pass elimination in the... 

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