A study of microemulsion systems for transdermal delivery of triptolide.
ABSTRACT Triptolide possesses immunosuppressive, anti-fertility and anti-cancer activities. Due to its severe toxicity, microemulsions with controlled, sustained and prolonged delivery of triptolide via a transdermal route are expected to reduce its adverse side effects. The purpose of the present study was to investigate the microemulsions for transdermal delivery of triptolide. The pseudo-ternary phase diagrams were developed and various microemulsion formulations were prepared using oleic acid as an oil, Tween 80 as a surfactant and propylene glycol as a cosurfactant. The droplet size of microemulsions was characterized by photocorrelation spectroscopy. The transdermal ability of triptolide from microemulsions was evaluated in vitro using Franz diffusion cells fitted with mouse skins and triptolide was analyzed by high-performance liquid chromatography. The effect of menthol as a permeation enhancer, and the loading dose of triptolide in microemulsions on the permeation rate were also evaluated. The triptolide-loaded microemulsions showed an enhanced in vitro permeation through mouse skins compared to an aqueous solution of 20% propylene glycol containing 0.025% triptolide. The permeation of microemulsions accorded with the Fick's first diffusion law. No obvious skin irritation was observed for the studied microemulsion ME6, but the aqueous solution of 20% propylene glycol containing 0.025% triptolide revealed the significant skin irritation. The results indicate that the studied microemulsion systems, especially ME6, may be promising vehicles for the transdermal delivery of triptolide.
Article: Penetration enhancers.[show abstract] [hide abstract]
ABSTRACT: One long-standing approach for improving transdermal drug delivery uses penetration enhancers (also called sorption promoters or accelerants) which penetrate into skin to reversibly decrease the barrier resistance. Numerous compounds have been evaluated for penetration enhancing activity, including sulphoxides (such as dimethylsulphoxide, DMSO), Azones (e.g. laurocapram), pyrrolidones (for example 2-pyrrolidone, 2P), alcohols and alkanols (ethanol, or decanol), glycols (for example propylene glycol, PG, a common excipient in topically applied dosage forms), surfactants (also common in dosage forms) and terpenes. Many potential sites and modes of action have been identified for skin penetration enhancers; the intercellular lipid matrix in which the accelerants may disrupt the packing motif, the intracellular keratin domains or through increasing drug partitioning into the tissue by acting as a solvent for the permeant within the membrane. Further potential mechanisms of action, for example with the enhancers acting on desmosomal connections between corneocytes or altering metabolic activity within the skin, or exerting an influence on the thermodynamic activity/solubility of the drug in its vehicle are also feasible, and are also considered in this review.Advanced Drug Delivery Reviews 04/2004; 56(5):603-18. · 12.89 Impact Factor
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ABSTRACT: Triptolide (TP) has been shown to have anti-inflammatory, immunosuppressive, anti-fertility and anti-neoplastic activities. However, its clinical use is restricted to some content due to its poor water solubility and some toxic effects. In order to find innovative ways for administering TP and alleviating its disadvantages, the controlled release delivery systems such as solid lipid nanoparticle (SLN) and microemulsion have been developed. In the present paper we describe the preparation and some characterization of specialized delivery systems for TP. The transdermal delivery capacity and anti-inflammatory activity were also evaluated. The results indicated that these SLN dispersions and microemulsions could serve as efficient promoters for the TP penetrating into skin. Furthermore, different formulations were optimized in this study. The best formulation of SLN dispersion consisted of 5% tristearin glyceride, 1.20% soybean lecithin and 3.60% polyethylene glycol (400) monosterate, while the best formulation of microemulsion consisted of 40% isopropyl myristate, 50% Tween-80: 1,2-propylene glycol (5:1, v/v) and water. The steady-state flux (Js) and permeability coefficient (Kp) of triptolide for the SLN dispersion of the first 6 h were 3.1+/-0.4 microg/cm2 per h and 0.0124+/-0.001 cm/h or 6.4+/-0.7 microg/cm2 per h and 0.0256+/-0.002 cm/h for the microemulsion, which was 3.45 and 7.02 times higher than those of triptolide solution, respectively. The anti-inflammatory activity of SLN dispersion was stronger than that of microemulsion in carrageenan induced rat paw edema. However, the results were the reverse in complete Frenud's adjuvant induced paw edema. Further investigations should be carried out on the toxicity of different formulations of triptolide to tissues.European Journal of Pharmaceutics and Biopharmaceutics 10/2003; 56(2):189-96. · 3.83 Impact Factor
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ABSTRACT: An ethyl laurate-based microemulsion system with Tween 80 as surfactant, propylene glycol and ethanol as cosolvents was developed for intranasal delivery of diazepam. Phase behavior and solubilization capacity of the microemulsion system were characterized and in vivo nasal absorption of diazepam from microemulsion formulations was investigated in rabbits. A single isotropic region, which is considered as a bicontinuous microemulsion, was found in the pseudo-ternary phase diagrams developed at various Tween 80: propylene glycol: ethanol ratios. With the increase of Tween 80 concentration, the microemulsion region area, microemulsion viscosity, and the amount of H(2)O and ethyl laurate solubilized into the microemulsion system increased; however, the increase of ethanol percentage produced opposite effects. Diazepam, a practically water-insoluble drug, displayed a high solubility of 41 mg/ml in a microemulsion consisting of 15% ethyl laurate, 15% H(2)O, and 70% (w/w) surfactant/cosurfactant (Tween 80:propylene glycol:ethanol at 1:1:1 weight ratio). Nasal absorption of diazepam from this microemulsion was found to be fairly rapid. At 2 mg/kg dose, the maximum drug plasma concentration was arrived within 2-3 min, and the bioavailability (0-2 h) after nasal spray compared with intravenous injection was about 50%. These results suggest that this ethyl laurate-based microemulsion may be a useful approach for the rapid-onset delivery of diazepam during the emergency treatment of status epilepticus.International Journal of Pharmaceutics 05/2002; 237(1-2):77-85. · 3.46 Impact Factor