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    Formulation, in-vitro release and transdermal diffusion of alpha-lipoic acid

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    Date
    2009
    Author
    Snyman, Tizane
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    Abstract
    Acne is a common disease characterised by follicular hyperkeratinisation, bacterial hipercolonisation as well as immune reactions and inflammation. In acne, reactive oxygen species (ROS) may be released from the damaged follicular walls, which could cause the advancement of inflammation in the pathogenesis of the disease. The topical application of antioxidants is a promising approach to support the endogenous antioxidant defence and avoid oxidative injury that may lead to acne. The skin provides a painless and patient-friendly approach for systemic drug administration. Transdermal drug delivery not only improves patient compliance, but also avoids the first-pass effect. The major hurdle to penetration of matter through the skin is provided by an outward layer of the skin, the stratum corneurm (SC). Overcoming this barrier safely and reversibly is a fundamental problem in the field of transdermal drug delivery. Alpha-lipoic acid was utilised as the cosmeceutical active and can be classified in a mixed category of compounds that lie between cosmetics and drugs. Alpha-lipoic acid and its reduced form, dihydrolipoic acid, have been described as the "universal antioxidants" because of their capacity to quench a number of free radicals in both aqueous and lipid environments, their metal-chelating properties and ability to restore other antioxidants from their inactive form. The Pheriod™ system is a new manner of drug delivery aimed at overcoming the barrier function of the skin. It consists of vesicular structures, the sizes of which vary from 200-440 nm. These vesicles, prepared from customised essential fatty acids, were found to advance the efficacy of topically administered compounds. The aim of this study was to determine whether the Pheroid™ delivery system would enhance the transdermal delivery of formulations containing alpha-lipoic acid to the target site by performing Franz cell diffusion studies over a 12 hour period, followed by tape-stripping experiments. The results of the formulations containing Pheroid™ were compared to those of the formulations without Pheroid™. Experimental determination of transdermal flux of the alpha-lipoic acid formulations revealed that Pheroid™ improved the transdermal delivery of alpha-lipoic acid. The average flux of Pheroid™ cream from 0 to 2 hours wass 58.01 ± 6.63 µg/cm2.h. The average flux of Pheroid™ gel from 4 to 12 hours was 22.18 ± 3.33 µg/cm2.h. Tape-stripping experiments proved that the concentrations of alpha-lipoic acid in Pheroid™ cream and cream that remained in the epidermis after application to the skin were 569.10 µg/ml and 764.93 µg/ml respectively. The concentrations of alpha-lipoic acid in Pheroid gel and gel that diffused into the dermis were 23.62 µg/ml and 61.06 µg/ml respectively. Aqueous solubility and log D partition coefficient of alpha-lipoic acid were determined. Inspection of the log D value of -0.78 indicated that the compound was unfavourable to penetrate the skin, whereas the aqueous solubility of 8.602 mg/ml in PBS at a temperature of 32 °C indicated favourable penetration.
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    http://hdl.handle.net/10394/3985
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    • Health Sciences [2073]

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