Drug delivery systems vehicle selection

Chloroform can also permeate the stratum comeum of rabbit skin (Torkelson et al. 1976) and mouse skin (Tsuruta 1975). Percutaneous absorption of chloroform across mouse skin was calculated to be approximately 38 pg/min/cm, indicating that the dermal absorption of chloroform occurs fairly rapidly in mice. No reliable studies report the percutaneous absorption of chloroform in humans however, a few clinical reports indicate that chloroform is used as a vehicle for drug delivery (King 1993). Islam et al. (1995) investigated the fate of topically applied chloroform in male hairless rats. For exposures under 4 minutes, chloroform-laden water was applied to shaved back skin for exposures of 4-30 minutes, rats were submerged in baths containing chloroform-laden water. Selected skin areas were tape-stripped a various number of times after various delay periods. It appeared that there was an incremental build-up of ehloroform in the skin over the first four minutes. When compared to uptake measured by bath concentration differences, approximately 88% of lost chloroform was not accounted for in the stratum comeum and was assumed to be systemically absorbed. 

Dehvering pharmaceutical agents to specific cells in the body is a difficult task involving complex interactions between many elements. Delivery systems have several fundamental requirements to achieve this task. The delivery vehicle must be ingesti-ble, implantable, or injectable to introduce the dmg into the body. The system must then protect the drug from the body s defense mechanisms in order to accumulate in selected cells. Once at the target, the delivery system should release the enclosed pharmaceutical agent with a controllable and predictable profile. Finally, the delivery vehicle should be biocompatible, nontoxic, and easily eliminated from the body. 

The selection of a vehicle can dramatically affect delivery and consequently efficacy of topical preparations. In terms of transdermal delivery, where delivering therapeutic agents for systemic effects is desired, solvents and co-solvent systems are widely used to improve both the amount and range of drugs that can be administered at therapeutic levels through the skin. Vehicles used in transdermal systems, such as patches, have recently been reviewed (Williams, 2003). In contrast, the focus of this chapter is on the use of solvents in topical dosage forms, i.e. preparations intended for a local or regional effect on the skin. 

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