Transdermal applications, lipids

Azone (laurocapram) is used extensively as a transdermal permeation enhancer, and has also found use in buccal drug delivery. It is a lipophilic surfactant in nature (Figure 10.4). Permeation of salicylic acid was enhanced by the pre-application of an Azone emulsion in vivo in a keratinized hamster cheek pouch model [35]. Octreotide and some hydrophobic compounds absorption have also been improved by the use of Azone [36], Azone was shown to interact with the lipid domains and alter the molecular moment on the surface of the bilayers [37], In skin it has been proposed that Azone was able to form ion pairs with anionic drugs to promote their permeation [38],... 

Changes in barrier function due to skin disease generally result either from alteration of the lipid/protein composition of the stratum comeum or from abnormal epidermal differentiation (e.g. in psoriasis). As far as transdermal bioavailability is concerned, however, patches intended for systemic therapy are labelled for application only at normal skin sites, free from dermatologic pathology. 

It must be stressed that both transdermal flux and Kp are not only chemical dependent but also tightly constrained by the membrane system studied as well as the method of topical application (neat compound, vehicle, length of experiment, etc.). The PC that is integral to Kp is the PC between the surface or applied vehicle and the stratum comeum. Different vehicles will thus result in different PCs. Similarly, skin from different species may result in different PCs due to differences in the stratum comeum lipids and intercellular path lengths. 

The chitosan and its derivatives show no acute toxicity and are not absorbed via transdermal route. The European pharmacopoeia contains a single monograph on chitosan hydrochloride. In the United States, chitosan is currently being included in the US Pharmacopoeia [Sarmento and das Neves, 2012]. The chitosan and its derivatives are deemed safe for use as permeation enhancer for transmucosal delivery of hydrophilic drugs and offer promising prospects for novel pharmaceutical applications [Junginger and Verhoef, 1998]. Despite the chitosan and its derivatives interact with lipids and proteins of the membranes of stratum corneum, they may not penetrate into deeper layers of the skin. This can be inferred from the absence of skin irritation by chitosan and its derivatives in Draize test [Aoyagi et al., 1991]. 

Because of the low permeability of the skin to many drugs, trans-dermal delivery has limited applications. The low permeability is attributed primarily to the stratum comeum, the outermost skin layer which consists of flat, dead cells filled with keratin fibers surrounded by lipid bilayers. One common method of increasing the passive transdermal diffusional drug flux involves pretreating the skin with a skin permeation enhancer. 

In absorption studies, the appUcation of colloidal systems, which show specific and unspecific interactions with mainly lipophilic substances is of main interest. An obvious application is the study of lipophilic and poorly absorbable drugs that are administered orally or transdermally. Such interactions with surface-active agents may either cause a diminution of the bioavailability by trapping the drug in the micelle or, on the other hand, lead to an improved solubility (prevention of the precipitation of the drug) and facilitated transfer of the solute across lipid membranes (e.g., the intestinal wall in the gastrointestinal tract) and therefore to an improved bioavailability. 

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