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      Ondansetron HCl Microemulsions for Transdermal Delivery: Formulation and In Vitro Skin Permeation

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          Abstract

          Ondansetron HCl delivery through oral route suffers due to its low bioavailability due to first-pass metabolism. Therefore, the microemulsion-based transdermal delivery may be a better substitute for it. The pseudoternary phase diagrams were constructed to determine compositions of microemulsions, and ondansetron HCl microemulsions for transdermal delivery were developed using isopropyl myristate or oleic acid as the oil phase, Tween 80 as the surfactant, and isopropyl alcohol as the cosurfactant evaluated for in vitro skin permeation through excised porcine skin. The in vitro skin permeation from these formulated microemulsions was sustained over 24 hours. The microemulsion F-8 (contained 10% of isopropyl myristate as oil phase, 8% of aqueous phase, and 82% of surfactant phase containing Tween 80 and isopropyl alcohol, 3 : 1) showed the highest permeation flux of 0.284 ± 0.003  μg/cm 2/hour. All these microemulsions followed the Korsmeyer-Peppas model ( R 2 = 0.971  to  0.998) with non-Fickian, “anomalous” mechanism over a period of 24 hours.

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          Most cited references25

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          Novel mechanisms and devices to enable successful transdermal drug delivery.

          B.W. Barry (2001)
          Optimisation of drug delivery through human skin is important in modern therapy. This review considers drug-vehicle interactions (drug or prodrug selection, chemical potential control, ion pairs, coacervates and eutectic systems) and the role of vesicles and particles (liposomes, transfersomes, ethosomes, niosomes). We can modify the stratum corneum by hydration and chemical enhancers, or bypass or remove this tissue via microneedles, ablation and follicular delivery. Electrically assisted methods (ultrasound, iontophoresis, electroporation, magnetophoresis, photomechanical waves) show considerable promise. Of particular interest is the synergy between chemical enhancers, ultrasound, iontophoresis and electroporation.
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            Influence of microemulsions on cutaneous drug delivery.

            In attempt to increase cutaneous drug delivery, microemulsion vehicles have been more and more frequently employed over recent years. Microemulsion formulations have been shown to be superior for both transdermal and dermal delivery of particularly lipophilic compounds, but also hydrophilic compounds appear to benefit from application in microemulsions compared to conventional vehicles, like hydrogels, emulsions and liposomes. The favourable drug delivery properties of microemulsions appear to mainly be attributed to the excellent solubility properties. However, the vehicles may also act as penetration enhancers depending on the oil/surfactant constituents, which involves a risk of inducing local irritancy. The correlation between microemulsion structure/composition and drug delivery potential is not yet fully elucidated. However, a few studies have indicated that the internal structure of microemulsions should allow free diffusion of the drug to optimise cutaneous delivery from these vehicles.
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              Passive skin penetration enhancement and its quantification in vitro.

              K. Moser (2001)
              The poor penetration of drugs into the skin (and, partially, the permeation across the stratum corneum) often limits the efficacy of topical formulations. Basically, skin penetration can be enhanced by the following strategies: (i) increasing drug diffusivity in the skin; (ii) increasing drug solubility in the skin, and/or (iii) increasing the degree of saturation of the drug in the formulation. In this article, we review the literature with respect to: (i) chemical penetration enhancers, which have been shown to influence the diffusivity and/or solubility of the drug in the skin and (ii) supersaturated formulations, in which the degree of saturation of the drug is increased compared to conventional formulations. In addition, three different in vitro methods, specifically, classic diffusion cell studies, attenuated total-reflectance-Fourier transform infrared spectroscopy, and tape stripping in conjunction with an appropriate analytical technique, are considered, emphasizing their application to obtain quantitative values for skin transport parameters and to separate the kinetic or thermodynamic effects of an enhancement strategy.
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                Author and article information

                Journal
                ISRN Pharm
                ISRN Pharm
                ISRN.PHARMACEUTICS
                ISRN Pharmaceutics
                International Scholarly Research Network
                2090-6145
                2090-6153
                2012
                19 June 2012
                : 2012
                : 428396
                Affiliations
                1Department of Pharmaceutics, Bengal College of Pharmaceutical Science and Research, Durgapur 713212, India
                2Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Mayurbhanj 757086, India
                Author notes

                Academic Editors: M. AghazadehTabrizi, R. Lesyk, and S. Velaga

                Article
                10.5402/2012/428396
                3388345
                22779009
                7c61d824-5d36-4ba4-9a21-077ef65adad2
                Copyright © 2012 Jadupati Malakar et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 March 2012
                : 6 May 2012
                Categories
                Research Article

                Pharmacology & Pharmaceutical medicine
                Pharmacology & Pharmaceutical medicine

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