Microemulsions mediated effective delivery of methotrexate hydrogel: more than a tour de force in psoriasis therapeutics

Methotrexate (MTX), a well known drug for the treatment of cancer and rheumatoid arthritis, has gained prominence in the treatment of psoriasis over the period of years. However, the present mode of systemic administration through oral or parenteral route has always proposition, full of compromises. The toxicity of drug to the vital organs and physiological environment is the major concern. Also, its poor skin penetration is one major problem. Hence novel system based on lipid carriers has been considered here to overcome the barriers. Microemulsions (MEs) were prepared using pseudo-ternary phase diagram (PTPD) and they were characterized for various parameters such as size, shape (cryo-SEM), PDI, zeta potential, etc. The chosen MEs system (optimized) was then incorporated into secondary vehicles and characterized for rheological behavior, texture profile analysis, in vitro release, ex vivo permeation and drug distribution into different layers of skin. The developed formulations were further evaluated in ex vivo and in vivo such as cell line study, imiquimod-induced psoriatic model, allergic contact dermatitis, rat tail model (% orthokeratosis) and safety test (Draize test). The MEs based MTX gel has shown its potential in locating the drug at the desired domain of stratum corneum, epidermal and dermal layers of skin and reducing systemic absorption. Our results are suggestive of MEs potential as a novel carrier for topical delivery of MTX in topical therapeutic and safety approaches. In conclusion, developed MEs-based hydrogel has shown promising results in achieving effective delivery of MTX.     

微乳作为皮肤局部用药载体的研究进展

微乳是目前药剂学研究的热点,通过皮肤给药以达到局部或全身治疗目的的1种给药载体。综述近年来国内外对微乳作为皮肤局部用药载体的作用机制、影响因素、评价方法以及临床应用等方面的研究进展。     

新型药物剂型——微乳

对近期国内外的文献报道进行检索、分类和整理.系统地综述微乳的处方组成及其制备工艺,在药剂中的应用及存在的问题.微乳制剂在药剂学中将有较好的应用前景.     

Development and pharmacokinetic evaluation of erythromycin lipidic formulations for oral administration in rainbow trout (Oncorhynchus mykiss)

The aim of this work was to enhance the bioavailability of erythromycin base when administered orally in rainbow trout (Oncorhynchus mykiss). Since erythromycin is normally given in the form of medicated feed, in this study three new types of feed formulation were developed. A self-emulsifying system and two types of double microemulsions (O/W/O) were prepared, characterized and adsorbed on a commercial extruded diet for fish. The emulsified systems were based on saturated polyglycolized glycerides and mono- and diglycerides of medium-chain fatty acids (as oily phase), Tween® 80 (as surfactant) and, in the case of double microemulsions, distilled water. The systems differed in percentage composition and for the amount and position of erythromycin in different phases. The three medicated feed were then administered orally by means of a gastric probe to rainbow trout and their relative bioavailability was estimated in comparison with that obtained after oral administration of feed with erythromycin powder. For each medicated feed, 80 fish were tested. Finally, plasma profiles of erythromycin after single administration of medicated feeds were used to predict profiles obtainable by administering once-daily medicated feeds for 7 consecutive days. The results proved that the feeds containing microemulsified erythromycin provided largely superior oral bioavailability and the advantage of obtaining the same efficacy against bacterial infections with a much lower dose of drug.     

Applications of microemulsions in cosmetics

Since microemulsions were discovered approximately six decades ago, their applications in several fields, including cosmetics, have been increased due to their good appearance, thermodynamic stability, high solubilization power, and ease of preparation. In addition, microemulsions can enhance skin permeation of the loaded substances. They are classified into three types: oil-in-water, bicontinuous, and water-in-oil. All types of microemulsions can be formed spontaneously when the ratios of oil, water, and amphiphile in the systems are appropriate. These proper ratios can be found in a microemulsion region of a phase diagram. The efficiency of microemulsions in topical application is related to microemulsion type. Microemulsion characterization needs a combination of the data from several experimental techniques. Numerous applications of cosmetic microemulsions include skin-care, hair-care, and personal-care products for improving the product efficiency and stability. Moreover, new materials have been developed to be used in cosmetic microemulsion formulations for increasing the product efficiency and reducing the toxicity. The aim of this review is to present some basic information of microemulsions and novel applications of microemulsions in cosmetic formulations.     

Mass Transport Properties of Progesterone and Estradiol in Model Microemulsion Formulations

Purpose The purpose of these studies was to determine the extent to which drug loading influences the mass transport characteristics of poorly soluble steroids from model microemulsion formulations in vitro.Methods Two conditions of drug loading in the microemulsions were tested, “near saturation” and “constant loaded.” Mass flux of ³H-labelled progesterone or estradiol was measured in a side-by-side diffusion chamber from microemulsions consisting of Brij 97, Miglyol 812 and water. Pulsed gradient NMR was used to measure the diffusivities of all components. The thermodynamic activity and fraction of free drug in the formulations were measured by polymer uptake. Solute flux was calculated employing an aqueous boundary layer model.Results Under near saturation loading, all microemulsion formulations showed significantly increased flux of steroids compared to the saturated aqueous solution. For both steroids flux values in the 0.5 and 1% systems were significantly lower for the 3% oil formulation, despite the observation that the 3% formulation held significantly more drug. On the other hand, for all the formulations under constant drug loading, solute flux was only moderately increased for progesterone and not at all for estradiol when compared to the saturated aqueous solution. Under both loading conditions, thermodynamic activities did not correlate to flux indicating some other factor was modulating mass transport. Effective diffusivities of the steroids in formulations as determined by NMR were significantly reduced compared to those of the monomer drug in aqueous solution. In both near-saturated and constant-loaded conditions, the calculated values for progesterone flux were markedly similar to those observed experimentally suggesting solubilization and diffusion events in the aqueous boundary layer had a strong influence on mass transport. In contrast, calculations for estradiol were less successful in modeling the observed flux values.Conclusions In systems nearly saturated with drug, the microemulsion formulation leads to a greatly enhanced rate of steady-state mass transport while in systems with drug loading far from saturation, the microemulsion formulation appears to have a minimal ability to promote mass transport. The aqueous boundary layer diffusion model was successful in fitting progesterone results but was not successful for estradiol.     

N-trimethyl chitosan (TMC)-modified microemulsions for improved oral bioavailability of puerarin: preparation and evaluation

Abstract

The aim of this research was to increase the oral bioavailability of puerarin by N-trimethyl chitosan-modified microemulsions (TMC-MEs) loaded with puerarin. Different concentrations of TMC-modified microemulsions were prepared in our study, and then evaluated for particle size, zeta potential, morphological observation and changes of the microenvironment polarity of inner oil core. It was shown that the zeta potential of the microemulsion was increased with the increasing concentration of TMC, and the peak value was achieved when the concentration of TMC was 3.0?mg/mL. The enhancement of the ratio of I₁/I₃ (the ratio between the first band and the third band of the emission fluorescence spectrum of pyrene, I₁?=?373?nm, I₃?=?384?nm) indicated that polarity of the inner core of TMC-MEs was increased with the addition of the modifier. Pharmacokinetic studies demonstrated that after oral administration of puerarin N-trimethyl chitosan (TMC)-modified microemulsions (PUE-TMEs) and puerarin microemulsions (PUE-MEs) to rats at a dose of 100?mg/kg, relative bioavailability was enhanced about 6.8- and 1.2-fold, respectively, compared to puerarin suspension (PUE-SUS) as control. It indicated that the TMC-MEs could be used as an effective formulation for enhancing the oral bioavailability of puerarin.     

三七总皂苷微乳在家兔眼部的药动学研究

目的研究三七总皂苷微乳在家兔眼部的药动学。方法微透析探针植入家兔眼前房室内,灌流平衡1 h,耳缘静脉注射微乳和注射用血栓通(冻干)。然后,LC-MS/MS法测定不同时间点(0.5、1、1.5、2、2.5、3、3.5、4、4.5、5、5.5、6、7、8 h)人参皂苷Rg₁、三七皂苷R₁含有量。结果微乳组人参皂苷Rg₁、三七皂苷R₁的C_max、AUC_{0～8 h}、AUC_0～∞高于注射用血栓通(冻干)组(P<0.01),V_z/F、CL/F降低(P<0.05,P<0.01),这2种成分生物利用度分别为(290.62±63.64)%、(587.78±148.07)%。结论三七总皂苷微乳可提高药物在家兔眼部的生物利用度,为其进一步研发奠定了基础。