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Characterization and evaluation of an oral microemulsion containing the antitumor diterpenoid compound ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid

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      The objective of this study was to develop an oral microemulsion formulation of the antitumor diterpenoid agent, ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (henceforth referred to as 5F), to enhance its bioavailability and evaluate its hepatotoxicity. Pseudoternary phase diagrams showed that the optimal microemulsion formulation contained 45% water, 10% castor oil as the oil phase, 15% Cremophor EL as the surfactant, and 30% as a cosurfactant mixture of 1,2-propanediol and polyethylene glycol (PEG)-400 (2:1, w/w). The microemulsion preparation was characterized and its droplet diameter was within 50 nm. Release of 5F in vitro from the microemulsion was slightly increased compared with a suspension containing the same amount of active drug. Pharmacokinetic parameters in vivo indicated that bioavailability was markedly improved, with the relative bioavailability being 616.15% higher for the microemulsion than for the suspension. Toxicity tests showed that the microemulsion had no hepatotoxicity in mice. These results suggest the potential for 5F microemulsion to be administered by the oral route.

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      Microemulsions for topical delivery of estradiol.

      Estradiol has been widely used for the treatment of hormonal insufficiencies. Due to its extensive first pass metabolism after oral administration, transdermal administration of estradiol in gels and emulsions has been used to improve its bioavailability, prolong activity and to optimize metabolic profile. The purpose of this study was to investigate microemulsions as delivery systems for estradiol. Various o/w microemulsions were used to deliver estradiol across human abdominal skin in vitro. Trasdermal flux of estradiol was determined using Franz-type diffusion cells and the samples were analyzed by high-performance liquid chromatography (HPLC). The permeation data showed that microemulsion formulations increased estradiol flux 200-700-fold over the control, but permeability coefficients were decreased by 5-18 times. The superior transdermal flux of estradiol was due to 1500-fold improvement in solubilization of estradiol by microemulsions. The results suggest that microemulsions are potential vehicles for improved topical delivery of estradiol. Copyright 2002 Elsevier Science B.V.
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        Transdermal delivery of hydrocortisone from eucalyptus oil microemulsion: effects of cosurfactants.

        This study investigated the effects of cosurfactants on the transdermal delivery of hydrocortisone (model drug) from eucalyptus oil microemulsion. Eucalyptus oil which was successfully employed for steroidal drugs was used as the oil. Tween 80 which was readily miscible with eucalyptus oil was used as surfactant. Ethanol, isopropanol and propylene glycol which are relatively tolerable by the skin were employed as cosurfactants. Pseudo-ternary phase diagrams were constructed in the presence and absence of cosurfactants. Microemulsion formulations containing 20% oil, 20% water and 60% of either Tween 80 or 1:1 surfactant/cosurfactant mixture were compared. Incorporation of cosurfactants expanded the microemulsion zone. The cosurfactant free microemulsion was viscous showing pseudo-plastic flow. The cosurfactant containing preparations were less viscous with Newtonian flow. The drug loading and release rate were increased in the presence of cosurfactants with the release depending on the viscosity. Incorporation of hydrocortisone in microemulsion increased the transdermal flux compared to saturated aqueous solution. The presence of cosurfactants increased the transdermal drug flux compared to the cosurfactant free formulation. Ethanol produced the greatest effect followed by propylene glycol and isopropanol. The presence of cosurfactant and its type can thus affect both the phase behavior and the transdermal delivery potential of microemulsion.
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          Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin, and absorption studies in rats.

          This study describes the development and characterization of self-microemulsifying drug delivery systems (SMEDDS) in liquid and pellet forms that result in improved solubility, dissolution, and in vivo oral absorption of the poorly water-soluble compound curcumin. Solubility of curcumin was determined in various vehicles, including oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were constructed to identify the most efficient self-emulsification region. The optimized SMEDDS used for curcumin formulations in liquid and pellet forms contained 70% mixtures of two surfactants: Cremophor EL and Labrasol (1:1), and 30% mixtures of oil: Labrafac PG and Capryol 90 (1:1). The curcumin-SMEDDS in liquid and pellet formulations rapidly formed fine oil-in-water microemulsions, with particle size ranges of 25.8-28.8 nm and 29.6-32.8 nm, respectively. The in vitro rate and extent of release of curcumin from liquid SMEDDS and SMEDDS pellets was about 16-fold higher than that of unformulated curcumin. Plasma concentration-time profiles from pharmacokinetic studies in rats dosed with liquid and pelleted SMEDDS showed 14- and 10-fold increased absorption of curcumin, respectively, compared to the aqueous suspensions of curcumin. Curcumin-SMEDDS liquid and curcumin-SMEDDS pellets were found to be stable up to 6 months under intermediate and accelerated conditions. These studies demonstrate that the new self-microemulsifying systems in liquid and pellet forms are promising strategies for the formulation of poorly soluble lipophilic compounds with low oral bioavailability.

            Author and article information

            [1 ]Department of Chemistry, East China University of Science and Technology, Shanghai
            [2 ]Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical College, Zhanjiang, People’s Republic of China
            Author notes
            Correspondence: Yingnian Lu, Department of Chemistry, East China University of Science and Technology, Shanghai 200237, People’s Republic of China, Tel +86 759 2388405, Fax +86 759 2388305, Email Lyn7591@
            Int J Nanomedicine
            Int J Nanomedicine
            International Journal of Nanomedicine
            Dove Medical Press
            10 May 2013
            : 8
            : 1879-1886
            © 2013 Lu et al, publisher and licensee Dove Medical Press Ltd.

            This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

            Original Research

            Molecular medicine

            antitumor, diterpenoid, microemulsion, pharmacokinetics, toxicity


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