Stratum corneum hydrophilic drugs into

The particles of cyclodextrin-grafted silicone are also the vehicles for the transport of the active substance to the site of its therapeutic action. In the case of anti-fnngal dosage form for topical administration action, penetration and slow release in the skin is searched for [21-23]. The stratum corneum top layer is made of cor-neocytes separated by a lipidic intercellular medium. Internal layers, epidermis and dermis are essentially aqueous media. The top layer is hydrophobic whereas the internal layers are hydrophilic. The penetration into the skin is controlled by the hydrophobic character of the particles. Hydrophobic materials easily penetrate and possibly accumulate in the stratum corneum. A slow release of the drug into the deep hydrophilic layers is possible from this medium. Silicone emulsions are often selected for cosmetic formulations because of the favorable spreading of silicone oils at the skin surface together with their low-irritancy properties. 

Stereoselectivity in the metabolism and percutaneous permeation, related to skin enzymatic activity, was reported for several compounds [23-28]. Stereoselectivity in permeation and cutaneous hydrolysis of several ester prodrugs of propranolol through hairless mouse skin was investigated [23]. The authors reported the stereoselective hydrolysis of propranolol prodrugs that is notably biased towards the R-isomer, which resulted in the enantioselective permeation. The lipophilicity of prodrugs, expressed as the partition coefficients, was found to affect the apparent skin permeability coefficients. The more lipophilic prodrugs readily entered into the stratum corneum, but their clearance into hydrophilic deeper strata (epidermis and dermis), where drug hydrolysis takes place, was much less effective. Unlike S-isomers, the R-isomers of propranolol esters were entirely hydrolyzed in epidermis and freely crossed the dermis strata. 

The epidermis is an epithelium consisting of inner viable epidermis, a living hydrophilic layer, and outer nonviable epidermis, a hydrophobic layer made from dead cells. It is differentiated into stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale In the direction of dermis (Fig. 16.2). The viable epidermal layer has a thickness of about 0.02 to 0.2 mm. It is composed of many layers of keratinocytes, a widespread distribution of melanocytes, Langerhans cells, dendritic T cells, epidermotropic lymphocytes and Merkel cells, and a number of catabolic enzymes such as esterases, proteases, phosphatases, nucleotidases and lipases [Walters and Roberts, 2002 Barry, 2001). The outer and nonviable epidermis, namely, stratum corneum, is about 10 to 20 pm thick [Gregor and Ulrich, 2010). The stratum corneum Is deemed to be the major obstacle of drug permeation. 

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]. 

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