Development and in vitro–in vivo evaluation of a water-in-oil microemulsion formulation for the oral delivery of troxerutin

Objective: The main objective of this study was to develop and evaluate a W/O microemulsion formulation of troxerutin to improve its oral bioavailability.

Methods: The W/O microemulsion was optimized using a pseudo-ternary phase diagram and evaluated for physical properties. In vitro MDCK cell permeability studies were carried out to evaluate the permeability enhancement effect of microemulsion, and in vivo absorption of troxerutin microemulsion in the intestine was compared with that of solution after single-dose administration (56.7?mg/kg) in male Wistar rats.

Results: The optimal formulation consisted of lecithin, ethanol, isopropyl myristate and water (23.30/11.67/52.45/12.59 w/w) was physicochemical stable and the mean droplet size was about 50.20?nm. In vitro study, the troxerutin-loaded microemulsion showed higher intestinal membrane permeability across MDCK monolayer when compared with the control solution. The W/O microemulsion can significantly promote the intestinal absorption of troxerutin in rats in vivo, and the relative bioavailability of the microemulsion was about 205.55% compared to control solution.

Conclusion: These results suggest that novel W/O microemulsion could be used as an effective formulation for improving the oral bioavailability of troxerutin.     

An optimized commercially feasible milling technique for molecular encapsulation of meloxicam in β-cyclodextrin

Background: The practical applicability of solid dispersions (SD) for improvement of oral bioavailability of poorly water-soluble drugs has still remained limited because of lack of feasibility for scale-up of manufacturing processes. The present research work deals with the preparation of SDs of meloxicam (MLX) with β-cyclodextrin (β-CD) by the ball-milling technique to overcome the scale-up issues.

Methods: Phase-solubility studies were conducted to analyze the influence of β-CD on solubility of MLX. In vitro dissolution studies on various complexes as well as tablets prepared on pilot scale in an industrial set up were performed and compared with the marketed products. Physicochemical characterization of optimized complexes was done using various methods to study drug-β-CD interaction.

Results: Solubility of pure MLX in water at 25°C was found to be only 9.4 µg/mL. The AL type of phase-solubility profile of MLX with β-CD [stability constant (K_1:1)?=?22.056?M^?1 and Gibbs free energy (ΔF^o)?=?–7.665 KJ/mole] confirmed the solubility enhancement capability of β-CD. Milling time of 6?h was considered to be optimum and showed maximum enhancement of drug dissolution. The amorphous nature of the milled complex and mode of interaction of MLX with β-CD was confirmed by differential scanning calorimetry (DSC), x-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance spectrophotometry (¹HNMR). Tablets containing MLX-β-CD (1:1.5?M) milled complexes showed the best release (T_90%?=?10.94?min) compared to the marketed products (T_90% ≥ 450?min). Stability studies performed confirmed the integrity of the amorphous complex.

Conclusion: Stable inclusion complexes of MLX-β-CD with enhanced aqueous solubility and dissolution rate were prepared by a highly efficient and controlled large-scale milling technique.     

The influence of the structure and the composition of water/AOT-Tween 85/IPM microemulsion system on transdermal delivery of 5-fluorouracil

The purpose of this study was to investigate the influence of the structure and the composition of water/Aerosol-OT (AOT)-Tween 85/isopropylmyristate (IPM) microemulsion system (WATI) on transdermal delivery of 5-fluorouracil (5-FU). The structure of WATI was characterized by measuring surface tension, density, viscosity, electric conductivity, and differential scanning calorimetry. The effect of the drug loading, water content, component compositions and the amount of mixed surfactant on permeation of 5-FU through mice skin was evaluated by using Franz-type diffusion cells. The results in vitro implied that WATI was W/O microemulsion when the water content was below 20 wt% at fixed 20 wt% of mixed surfactant at 25°C, then might be transformed to a bicontinuous structure, finally, formed O/W microemulsion with water content over 30 wt%. Increase of the drug loading can directly facilitate the penetration of the drug across the skin. Drug diffusion after 12?h from the bicontinuous microemulsion (795.1?±?22.3 µg·cm^?2) would be fastest compared to that from the W/O microemulsion (650.2?±?11.7 µg·cm^?2) and the O/W microemulsion (676.6?±?14.8 µg·cm^?2). The combination of AOT and IPM could bring about synergistic effect on the skin enhancement, however, Tween 85 in WATI decreased the cumulative permeation amount of 5-FU. The content of mixed surfactant had no effect on the permeation of 5-FU at fixed surfactant/cosurfactant ratio (K_m?=?2). Thus, the increased transdermal delivery the hydrophilic drug of 5-FU was found to be concerned with both of the structure and the composition of WATI.     

The preparation of iron (III) oxide nanoparticles using W/O microemulsion

Iron (III) oxide, Fe₂O₃, nanoparticles were prepared using W/O microemulsion as the reactor. W/O microemulsion was formed using n-heptane as oil phase, water and AOT as the surfactant under the specific composition. Iron (III) Chloride was used as a starting material and Ammonium hydroxide was a precipitating agent. Fe₂O₃, nanoparticles were then produced in situ the water core. Size of particles could be adjusted by the water content of the mixtures. The higher the water content, the bigger the particle size. The average size of the nanoparticles obtained was smaller than 100 nm. Moreover, Fe₂O₃ produced by this method was hematite with hexagonal in structure.     

Microstructural characteristics of gas tungsten arc synthesised Fe-Cr-Si-C coating

Abstract

The gas tungsten arc (GTA) method was used to synthesise Fe-Cr-Si-C alloy coatings, and processing effects on the coating were investigated experimentally. Coatings were developed on an AISI type 1040 steel substrate. Four different regions were obtained in the surface coating; and in these regions either a hypoeutectic or a hypereutectic microstructure was found. The hypoeutectic microstructure consisted of primary dendrites of austenite (γ) phase and eutectic M₇C₃ (M=Cr,Fe) carbides. On the other hand, the hypereutectic microstructure consisted of M₇C₃ primary carbides and eutectic. A hypoeutectic or hypereutectic microstructure was determined by the combination of particularly carbon concentration, solidification rate, and extent of substrate melting. The higher hardness of the hypereutectic microstructure is attributed especially to the formation of M₇C₃ primary carbides. The lower hardness of the hypoeutectic microstructure is related to three effective parameters: first, the presence of γ phase in the primary dendrites; second, excessive dilution from the base material; and third, relatively low concentrations of chromium and carbon.     

Sintering behaviors,microstructures and dielectric properties of CaO-B2O3-SiO2 glass ceramic for LTCC application with various network modifiers content

CaO-B₂O₃-SiO₂ (CBS) glass ceramic with various glass network modifiers were synthesized to develop a kind of material sintered at low temperature for multi-layer ceramic substrates. The influence of double alkali metal oxides (Na₂O and K₂O) on sintering characteristics, microstructures and dielectric properties of CBS glass ceramic were investigated. XRD analysis showed that the major crystalline phase was β-CaSiO₃ and CaB₂O₄, and the strength of the peak increased with the addition of network modifiers. DSC curve revealed that the process of crystallization and softening were obviously affected. SEM photographs exhibited that the microstructures were composed of amorphous phases, pores and crystalline phases. FTIR showed that the additives changed the continuity of CBS glass structure. An appropriate amount of Na₂O and K₂O additives could significantly improve the sintering characteristics and dielectric properties. CBS samples with 1.5 wt% (Na₂O?+?K₂O) sintered at 850 °C for 15 min presented the best performances with the bulk density of 2.53 g/cm³, ε_r?=?5.94 and tanδ?=?1.22?×?10^?3 at 10 GHz.

     

Environmentally benign preparation of metal nano-particles by using water-in-CO2 microemulsions technology

Water-in-CO₂ (W/C) microemulsion technology offers a new environmentally friendly approach for the synthesis of a variety of metal nano-particles in supercritical CO₂ using water-soluble reagents as starting material. W/C microemulsions have unique advantages over conventional water-in-oil (W/O) microemulsions because of the use of environmentally benign, cheap, and recyclable CO₂ as the continuous phase in place of organic solvents. In this review, we will discuss some recent progress on the preparation and applications of metal nano-particles prepared in W/C microemulsions.     

Design of powder metallurgy aluminium alloys for applications at elevated temperatures Part 1 Microstructure of high pressure gas atomized powders

Abstract

A method is described for designing powder metallurgy rapidly solidified aluminium alloys using experimental and/or calculated nucleation maps which give the microstructure of gas atomised powders as a function of powder particle size and alloy composition. This method was used to predict the compositions of Al–Cr–Zr–Mn alloys for which the <45 μm sizefraction of the gas atomised powders exhibits a microstructure with or without Al₁₃Cr₂ intermetallic particles. Powders were produced by high pressure gas atomisation and were examined using analytical electron microscopy. The microstructures observed were in excellent agreement with those predicted. The powders exhibited four distinct microstructures with increasing powder particle diameter: (i) segregation free, (ii) cellular α aluminium, (iii) α aluminium plus fine spherical precipitates rich in chromium and manganese, and (iv) α aluminium plus Al₁₃Cr₂ primary intermetallic particles. The solidification of these powders is discussed in terms of solidification front velocity controlled by external heat flow and by the initial undercooling. Particles less than 10 μm in diameter undercool significantly before solidification. Segregation free microstructures occur in the fine <1 μm) particles, where the solidification front velocity exceeds the absolute stability velocity.

MST/1247a     

Influence of carbon on the formation of γ/γ′ microstructure and κ-phase in the WC/Co–Ni–Al–W system: ab initio calculations and experimental studies

Modifications of the binder phase (γ) of cemented carbides have the potential to increase the hardness and wear resistance of the whole material. Partially, coherent precipitations with L1₂ structure (γ’) promise these improved properties without sacrificing tensile strength or toughness. γ’ is a metastable phase in the Al–Co–W ternary system in the form of Co₃(Al,W) which is stabilized by the substitution of cobalt with nickel. Superalloys of the composition Co–(30Ni)–9Al–7 W with different carbon contents were prepared by inductive melting, and the resulting microstructures were analysed using SEM–EDS, XRD and Vickers hardness. Cemented carbides with γ/γ’ binder microstructure were prepared via DTA, and the phase equilibria in the composite material were investigated experimentally and in silico. It was shown that nickel stabilizes the γ’ phase in superalloys as well as in cemented carbides. Carbon leads to the formation of an additional phase with E2₁ structure (κ). DTA measurements of cemented carbides with different aluminium–cobalt–nickel mixtures as binder gave an overview of the compositional influence. Enthalpies of formation for compounds with L1₂ and E2₁ structure were calculated using ab initio methods and compared to experimental results.

Graphical Abstract

     

Formulation and characterization of Brucea javanica oil microemulsion for improving safety

Objective: This study engaged in investigation of optimal formulation, characteristics analysis of Brucea javanica oil microemulsion (BJOM) in order to address safety concerns and make recommendations for improvements in BJOM safety during clinical use in vivo.

Methods: Pseudo-ternary phase diagram techniques were used to determine the appropriate ratio of surfactant, cosurfactant and oil phases. Subsequent stability testing of BJOM was performed by dilution, centrifugation and accelerated stability testing. The results were expounded through additional assessment utilizing the classical thermostat method to establish the shelf life of the material. These results were utilized to evaluate the safety of BJOM by haemolytic, irritative and allergic testing in vitro. In addition, the cytotoxicity of BJOM was examined using the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), with particular emphasis given to potential uses in cancer treatment.

Results: The most suitable method of preparation for BJOM was found to be a one to one ratio (K_m 1:1) of Solutol HS15 surfactant matched with sorbitol cosurfactant in the ratio. The microemulsion droplets of BJOM possessed a spherical shape, uniform size and average diameter of 23.8?nm. The expiration date of BJOM was found to be 568?d. The safety study demonstrated no hemolysis activity at the experimental BJOM concentrations; however, mild hemolysis was observed at higher concentrations of Brucea javanica oil emulsion (BJOE), a common commercially available product. Irritation observed upon BJOM treatment can be primarily attributed to Brucea javanica oil (BJO) with little influence of BJOM excipients. In addition, BJOM caused no observed hypersensitivity or other visible allergic reactions in guinea pigs. The anticancer activity curves of BJOM and BJOE demonstrate that both BJOM and BJOE inhibit Hela cells, with BJOM demonstrating significantly more dramatic anticancer activity.

Conclusion: An optimal formulation of BJOM superior to commercially available products and safe for medical application such as intravenous injection has been outlined along with its anticancer activity rating.     

Xingnaojing mPEG2000-PLA modified microemulsion for transnasal delivery: pharmacokinetic and brain-targeting evaluation

Abstract

Xingnaojing microemulsion (XNJ-M) administered intranasally is used for stroke treatment. In order to decrease the XNJ-M-induced mucosal irritation, XNJ-M modified by mPEG₂₀₀₀-PLA (XNJ-MM) were prepared in a previous work. The present work aimed to assess the impact of mPEG₂₀₀₀-PLA on pharmacokinetic features and brain-targeting ability of XNJ-M. The bioavailability and brain-target effects of borneol and geniposide in XNJ-M and XNJ-MM were compared in mice after intravenous (i.v.) and intranasal (i.n.) administrations. Gas chromatography, high-performance liquid chromatography, and ultra-performance liquid chromatography/tandem mass spectrometry methods were developed for the quantification of borneol and geniposide. Blood and brain samples were collected from mice at different time points after i.v. and i.n. treatments with borneol at 8.0?mg/kg, geniposide at 4.12?mg/kg. In addition, near-infrared fluorescence dye, 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl indotricarbocyanine iodide was loaded into microemulsions to evaluate the brain-targeting ability of XNJ-M and XNJ-MM by near-infrared fluorescence imaging in vivo and ex vivo. For XNJ-M and XNJ-MM, the relative brain targeted coefficients (Re) were 134.59% and 198.09% (borneol), 89.70% and 188.33% (geniposide), respectively. Besides, significant near-infrared fluorescent signal was detected in the brain after i.n. administration of microemulsions, compared with that of groups for i.v. administration. These findings indicated that mPEG₂₀₀₀-PLA modified microemulsion improved drug entry into blood and brain compared with normal microemulsion: the introduction of mPEG₂₀₀₀-PLA in microemulsion resulted in brain-targeting enhancement of both fat-soluble and water-soluble drugs. These findings provide a basis for the significance of mPEG₂₀₀₀-PLA addition in microemulsion, defining its effects on the drugs in microemulsion.     

Study on microstructure and properties of Ni-based alloy/Y2O3-deposited metals by laser cladding

Laser cladding of Ni-based alloy/Y₂O₃ (Yttrium Oxide) powder on 6061 aluminum alloy was carried out using 3 kW CW Nd:YAG laser to strengthen and improve hardness and corrosion resistance of substrate. Metal matrix composite composed of aluminum substrate, Ni-based alloy, refining and dispersion strengthening Y₂O₃, and particle hardening W, Cr was obtained. The microstructure and morphology, phase identification, element diffusion, and composition analysis of the Ni-based alloy/Y₂O₃-deposited metal and deposited metals/6061 aluminum substrate interface were examined using scanning electron microscopy (SEM), Electron Probe Micro-analyzer (EPMA) with energy-dispersive spectrometer (EDS) analysis. The micro-hardness distribution and corrosion-resistance property were investigated also. The results showed: (1) with the addition of Y₂O₃, more fine microstructures consisted of isometric crystal, white acicular crystal, and fringe crystal, primary phases were mainly Ni₃Al, NiAl, NiAl₃, W, α-Al, and Cr _x C. (2) Micro-hardness of deposited metals was 780–1100 HV_0.2 and distributed smoothly near interface. The corrosion rate of aluminum substrate was nearly twice that of deposited metals with addition of Y₂O₃.     

Influence of Electron Beam Powder Bed Fusion Process Parameters at Constant Volumetric Energy Density on Surface Topography and Microstructural Homogeneity of a Titanium Aluminide Alloy

In powder bed fusion additive manufacturing, the volumetric energy density E _V is a commonly used parameter to quantify process energy input. However, recent results question the suitability of E _V as a design parameter, as varying the contributing parameters may yield different part properties. Herein, beam current, scan velocity, and line offset in electron beam powder bed fusion (PBF-EB) of the titanium aluminide alloy TNM–B1 are systematically varied while maintaining an overall constant E _V. The samples are evaluated regarding surface morphology, relative density, microstructure, hardness, and aluminum loss due to evaporation. Moreover, the specimens are subjected to two different heat treatments to obtain fully lamellar (FL) and nearly lamellar (NLγ) microstructures, respectively. With a combination of low beam currents, low-to-intermediate scan velocities, and low line offsets, parts with even surfaces, relative densities above 99.9%, and homogeneous microstructures are achieved. On the other hand, especially high beam currents promote the formation of surface bulges and pronounced aluminum evaporation, resulting in inhomogeneous banded microstructures after heat treatment. The results demonstrate the importance of considering the individual parameters instead of E _V in process optimization for PBF-EB.     

Albendazole solution formulation via vesicle-to-micelle transition of phospholipid-surfactant aggregates

Objective: To reveal the physicochemical mechanisms governing the solubilization of albendazole in surfactant and phospholipid-surfactant solutions and, on this basis, to formulate clinically relevant dose of albendazole in solution suitable for parenteral delivery.

Significance: (1) A new drug delivery system for parenteral delivery of albendazole is proposed, offering high drug solubility and low toxicity of the materials used; (2) New insights on the role of surface curvature on albendazole solubilization in surfactant and surfactant-phospholipid aggregates are provided.

Methods: The effect of 17 surfactants and 6 surfactant-phospholipid mixtures on albendazole solubility was studied. The size of the colloidal aggregates was determined by light-scattering. The dilution stability of the proposed formulation was assessed by experiments with model human serum.

Results: Anionic surfactants increased very strongly drug solubility at pH?=?3 (up to 4?mg/mL) due to strong electrostatic attraction between the oppositely charged (at this pH) drug and surfactant molecules. This effect was observed with all anionic surfactants studied, including sodium dodecyl sulfate, double chain sodium dioctylsulfosuccinate (AOT), and the bile salt sodium taurodeoxycholate. The phospholipid-surfactant mixture of 40% sodium dipalmitoyl-phosphatidylglycerol +60% AOT provided highest albendazole solubilization (4.4?mg/mL), smallest colloidal aggregate size (11?nm) and was stable to dilution with model human serum at (and above) 1:12 ratio.

Conclusions: A new albendazole delivery system with high drug load and low toxicity of the materials used was developed. The high solubility of albendazole was explained with vesicle-to-micelle transition due to the larger interfacial curvature preferred for albendazole solubilization locus.     

T4 热处理对石膏型 AZ91 铸造镁合金组织和性能的影响

用石膏型熔模铸造技术,成功制备了AZ91镁合金铸件.用金相显微镜(OM)、扫描电镜(SEM)、能谱(EDS)以及电子万能实验机等,研究了AZ91镁合金铸态及T4热处理态的显微组织演变和力学性能.结果表明,分布在铸态AZ91镁合金晶界的网状β-Mg17Al12相在T4热处理过程中逐渐溶解,铸态和T4热处理态中均存在大量的A18Mn5化合物,T4处理后,其力学性能显著提高.     

Effects of sintering temperature on the superconducting and microstructural properties of Bi1.7Pb0.4Sr1.6Ca2.4Cu3.6OY/Ag2O composites

The effects of sintering temperature on the superconducting and microstructure properties of Bi_1.7Pb_0.4Sr_1.6Ca_2.4Cu_3.6O _Y (BPSCCO)/Ag₂O (0–50 wt%) superconductors were investigated. Based on the differential thermal analysis data, it was found that the addition of Ag₂O to the BPSCCO system lowered the partial melting temperature (peritectic point), thereby promoting extra liquid formation in this system and affecting the stability of 2223 high-T _c phase of these composites. For example, the T _c (zero) of the BPSCCO/Ag₂O (10 wt%) composite which was sintered at 843 °C in air was depressed by as much as 52 K. However, the addition of Ag₂O (10–50 wt%) in the BPSCCO samples resulted in no significant effect on T _c when samples were treated under a lower sintering temperature (827 °C) in air. The correlations of superconducting properties with microstructures of these materials are discussed.     

Development and Characterization of Self-Microemulsifying Drug Delivery System of Tacrolimus for Intravenous Administration

Tacrolimus (FK 506), a poorly soluble immunosuppressant is currently formulated in nonaqueous vehicle containing hydrogenated castor oil derivative for intravenous administration. Hydrogenated castor oil derivatives are associated with acute anaphylactic reactions. This proposes to overcome the problems of poor aqueous solubility of the drug and the toxicity associated with currently used excipients by the development of a new parenterally acceptable formulation using self-microemulsifying drug delivery system (SMEDDS). Solubility of FK 506 in various oils, surfactants, and cosurfactants was determined to identify SMEDDS components. Phase diagrams were constructed at different ratios of surfactants: cosurfactant (K_m) to determine microemulsion existence area. Influence of oily phase content, K_m, aqueous phase composition, dilution, and incorporation of drug on mean globule size of microemulsions was studied. SMEDDSs were developed using ethyl oleate as oily phase and Solutol HS 15 as surfactant. Glycofurol was used successfully as a cosurfactant. Developed SMEDDS could solubilize 0.8% (wt/wt) FK 506 and on addition to aqueous phase could form spontaneous microemulsion with mean globule size < 30 nm. The resulting microemulsion was iso-osmotic, did not show any phase separation or drug precipitation even after 24 h, and exhibited negligible hemolytic potential to red blood cells.     

Neural network modelling of flow stress in Ti–6Al–4V alloy with equiaxed and Widmanstätten microstructures

Abstract

In the present study, artificial neural networks (ANNs) were used to model flow stress in Ti–6Al–4V alloy with equiaxed and Widmanstätten microstructures as initial microstructures. Continuous compression tests were performed on a Gleeble 3500 thermomechanical simulator over a wide range of temperatures (700–1100°C) with strain rates of 0˙001–100 s^–1 and true strains of 0˙1–0˙6. These tests have been focused on obtaining flow stress data under varying conditions of strain, strain rate, temperature, and initial microstructure to train ANN model. The feed forward neural network consisted of two hidden layers with a sigmoid activation function and backpropagation training algorithm was used. The architecture of the network includes four input parameters: strain rate ?, Temperature T, true strain ? and initial microstructure and one output parameter: the flow stress. The initial microstructure was considered qualitatively. The ANN model was successfully trained across (α+β) to β phase regimes and across different deformation domains for both of the microstructures. Results show that the ANN model can correctly reproduce the flow stress in the sampled data and it can predict well with the nonsampled data. A graphical user interface was designed for easy use of the model.     

Formulation and characterization of liquid crystal systems containing azelaic acid for topical delivery

Purpose: The aim of this study is to prepare and characterize azelaic acid (AzA) containing liquid crystal (LC) drug delivery systems for topical use.

Methods: Two ternary phase diagrams, containing liquid paraffin as the oil component and a mixture of two nonionic surfactants (Brij 721P and Brij 72), were constructed. Formulations chosen from the phase diagrams were characterized by polarized light microscopy, rheological analyses, differential scanning calorimetry (DSC), and small angle x-ray scattering spectroscopy.

Results: Polarized light microscopy proved that except the oil/water emulsion (O/W E), other formulations showed lamellar LC structure. In vitro release studies indicated that the fastest release was achieved by the Lamellar LC (LLC) and O/W E systems, whereas slower release was obtained from the emulsion containing lamellar LC (E-LLC) and distorted lamellar LC (D-LLC) systems. Results of rheological measurements both supported the results of in vitro release studies and showed that the emulsion containing the LC (E-LLC) system had the most stable structure. The formulations and their effect on stratum corneum (SC) were evaluated by DSC studies. The lamellar LC (LLC), emulsion containing lamellar liquid crystal (E-LLC), and O/W E formulations had an effect on both lipid and protein components of SC, whereas distorted lamellar liquid crystal (D-LLC) system had an effect on only the lipid components of SC.

Conclusions: LLC systems could be considered promising for the topical delivery of AzA.     

Preparation and evaluation of bicyclol microemulsions for enhanced oral bioavailability

Context: Bicyclol is a novel anti-hepatitis drug used for the treatment of chronic hepatitis B. Bicyclol is insoluble in water and poorly absorbed after oral administration. To date, formulation development studies to improve the in vitro dissolution profiles of bicyclol and the in vivo oral absorption characteristics have not been performed.

Objective: To overcome problems associated with the poor solubility and low oral bioavailability of bicyclol, a microemulsion system was prepared and evaluated in vitro and in vivo.

Methods: The solubility of bicyclol in various cosurfactants was determined. The optimized premicroemulsion concentrate consisted of transcutol, Tween 20, Cremophor RH 40, propylene glycol monocaprylate and bicyclol (ratio, 50:150:100:150:3). The in vitro solubility and dissolution profiles were determined, and the in vivo oral absorption pharmacokinetics were evaluated in rats (dose, equivalent to 25?mg/kg of bicyclol) in comparison with bicyclol suspended in 0.5% calcium-carboxymethylcellulose (Ca-CMC).

Results and conclusion: Of various cosurfactants tested, transcutol provided the most significantly increased solubility of bicyclol (>20?mg/ml). Bicyclol was rapidly dissolved from the premicroemulsion concentrate (approximately 80% within 10?min). Consistent with the improved in vitro profiles, the oral absorption of bicyclol was significantly increased for the premicroemulsion concentrate, i.e. AUC and C_max were increased by 7.7- and 7.2-fold, respectively, over control values. These findings demonstrate that the microemulsion may be a useful drug delivery system to improve the oral bioavailability of bicyclol.