Volumetric and Isentropic Compressibility Behavior of Ionic Liquid, 1-Propyl-3-Methylimidazolium Bromide in Acetonitrile,Dimethylformamide, and Dimethylsulfoxide at <Emphasis Type="Italic">T</Emphasis> = (288.15 to 308.15) K

Density and speed-of-sound data for 1-propyl-3-methylimidazolium bromide ([C₃mim][Br]) + acetonitrile (MeCN), [C₃mim][Br] + dimethylformamide (DMF), and [C₃mim][Br] + dimethylsulfoxide (DMSO) binary mixtures in the dilute concentration region are reported at T = (288.15 to 308.15) K. From these data, apparent molar volume, isentropic compressibility, excess molar volume, and isentropic compressibility deviation values have been calculated. Negative deviations from the ideal behavior of both molar volume and isentropic compressibility have been observed for all systems investigated in this study. It has been found that deviations from ideal behavior for the [C₃mim][Br] + MeCN system are larger than those for the [C₃mim][Br] + DMF system which, in turn, are larger than those for the [C₃mim][Br] + DMSO system. The results have been interpreted in terms of ion–dipole interactions and structural factors of the ionic liquid and investigated organic solvents.     

Use of 1-alkyl-3-methylimidazolium l-lactates as both ligand and reaction media for AGET ATRP of acrylonitrile

Chiral ionic liquids, [C₂mim][LLA], [C₄mim][LLA] and [C₆mim][LLA] were firstly applied as both ligand and reaction media for atom transfer radical polymerization using activators generated by electron transfer (AGET ATRP) of acrylonitrile (AN) with ascorbic acid (VC) as reducing agent in the presence of air. A small but clear increase of polyacrylonitrile (PAN) isotacticity was observed for AGET ATRP of AN in [C₆mim][LLA] than in [C₆mim][BF₄]. PAN isotacticity markedly increased with the content of [C₆mim][LLA]. Compared with in [C₂mim][LLA] and [C₄mim][LLA], the rate of AGET ATRP of AN in [C₆mim][LLA] was fastest and the polymerization was best controlled. Well-defined PAN with molecular weight at 76,590, relatively narrower distribution at 1.27 and higher isotacticity at 0.37 was successfully prepared in [C₆mim][LLA].     

Acetylation of β-cyclodextrin in ionic liquid green solvent

The ionic liquid (IL), 1-butyl-3-methylimidzolium bromide ([C₄mim]Br), synthesized under supercritical CO₂, was developed as a green solvent for the dissolution, regeneration and acetylation of β-cyclodextrin (β-CD). The dissolution of β-CD in [C₄mim]Br of 25 wt% could be reached at 25 °C. The acetylation of β-CD was carried out under acetic anhydride in [C₄mim]Br in the absence of catalyst. β-CD acetates with different degrees of substitution of 0.07–1.14 were obtained directly under the homogeneous reaction conditions. The reaction medium of IL applied can be easily recycled and reused after the synthesis of β-CD acetate. The effects of reaction time, temperature, and acetic anhydride/AGU on the acetylation of β-CD were investigated. The acetylated β-CD samples were characterized by NMR, FT-IR, and X-ray diffraction (XRD) spectroscopy. It is the first time that we have demonstrated that ILs can be used as an environmentally friendly solvent for the acetylation of β-CD, which will open a new route to acetylation of β-CD under green solvent without catalyst.     

[C_4mim][BF_4]粘度的模拟与实验

为了研究离子液体的粘度特性,以1-丁基-3-甲基咪唑四氟硼酸盐([C4mim][BF4])离子液体为研究对象进行模拟计算与实验测试.基于分子动力学原理,编译了离子液体粘度的模拟计算程序,对[C4mim][BF4]离子液体完成了粘度模拟计算.搭建了粘度测试系统,进行离子液体的粘度测试.通过实验数据与模拟数据的对比,验证了模拟结果的准确性.另外,根据模拟粘度值的拟合曲线,分析了离子液体粘度的变化规律.同时,通过与水粘度的比对研究,阐述了[C4mim][BF4]离子液体的粘度特点.     

Electroanalytical determination of trace chloride in room-temperature ionic liquids

The electroanalytical quantification of chloride in [C4mim][BF4], [C4mim][NTf2], and [C4mim][PF6] ionic liquids has been explored using linear sweep and square wave voltammetry. Cathodic stripping voltammetry at a silver disk electrode is found to be the most sensitive. The methodology is based on first holding the potential of the electrode at +2.0 V (vs Ag wire), to accumulate silver chloride at the electrode. On applying a cathodic scan, a stripping wave is observed corresponding to the reduction of the silver chloride. This stripping protocol was found to detect ppb levels of chloride in [C4mim][BF4], [C4mim][NTf2], and [C4mim][PF6]. Although other methods for chloride have been reported for [BF4](-)- and [PF6](-)-based ionic liquids, no methods have been reported for [NTf2](-) ionic liquids.     

Transdermal and Buccal Delivery of Methylxanthines Through Human Tissue In Vitro

ABSTRACT

We examined the in vitro permeation of central nervous stimulants—caffeine, theophylline, and theobromine across human skin with the aid of six chemical enhancers. It was found that oleic acid was the most potent enhancer for all three methylxanthines. Further optimization studies with different solvents showed that caffeine transport could be enhanced to give flux values up to 585 μg/cm².hr^?1. Theobromine and theophylline delivery rates proved insufficient. An additional study involving a buccal tissue equivalent showed that this membrane was more permeable than skin for all model actives tested and would offer an alternate way of delivery.     

Thermal Conductivity of Ionic Liquids: Measurement and Prediction

This study reports thermal-conductivity data for a series of [EMIM] (1-ethyl-3-methylimidazolium)-based ionic liquids (ILs) having the anions [NTf₂] (bis(trifluoromethylsulfonyl)imide), [OAc] (acetate), [N(CN)₂] (dicyanimide), [C(CN)₃] (tricyanomethide), [MeOHPO₂] (methylphosphonate), [EtSO₄] (ethylsulfate), or [OcSO₄] (octylsulfate), and in addition for ILs with the [NTf₂]-anion having the cations [HMIM] (1-hexyl-3-methylimidazolium), [OMA] (methyltrioctylammonium), or [BBIM] (1,3-dibutylimidazolium). Measurements were performed in the temperature range between (273.15 and 333.15) K by a stationary guarded parallel-plate instrument with a total measurement uncertainty of 3 % (k = 2). For all ILs, the temperature dependence of the thermal conductivity can well be represented by a linear equation. While for the [NTf₂]-based ILs, a slight increase of the thermal conductivity with increasing molar mass of the cation is found at a given temperature, the [EMIM]-based ILs show a pronounced, approximately linear decrease with increasing molar mass of the different probed anions. Based on the experimental data obtained in this study, a simple relationship between the thermal conductivity, molar mass, and density is proposed for the prediction of the thermal-conductivity data of ILs. For this, also densities were measured for [EMIM][OAc], [EMIM][C(CN)₃], and [HMIM][NTf₂]. The mean absolute percentage deviation of all thermal-conductivity data for ILs found in the literature from the proposed prediction is about 7 %. This result represents a convenient simplification in the acquisition of thermal conductivity information for the enormous amount of structurally different IL cation/anion combinations available.     

咪唑基离子液体[C_(14)mim]Br对LLDPE结构与性能的影响

应用离子液体[C14mim]Br和线型低密度聚乙烯(LLDPE)熔融共混,制备出LLDPE/[C14mim]Br共混物,并对共混物结构与性能进行了表征与测试。结果表明,随着[C14mim]Br在共混物中含量的增加,LLDPE晶粒尺寸变大,而且在相同的降温速率下,[C14mim]Br使LLDPE起始结晶温度提高,表明[C14mim]Br起到了异相成核的作用。[C14mim]Br加入量为2.0 phr时,材料抗静电性能最好,表面电阻为1.8×108Ω。随着[C14mim]Br添加量的增加,材料的熔融指数有增加的趋势,而且材料拉伸强度先增大,后逐渐减小,冲击强度先减小,后逐渐增大,[C14mim]Br起到了反增塑与增塑的作用。     

Influence of Drug Lipophilicity on Terpenes as Transdermal Penetration Enhancers

Percutaneous absorption-enhancing effects on the skin of hairless mice of 11 monoterpenes [1, (+)-limonene; 2, (?)-menthone; 3, (+)-terpinen-4-ol; 4, α-terpineol; 5, 1,8-cineole; 6, (+)-carvone; 7, (?)-verbenone; 8, (?)-fenchone; 9, p-cymene; 10, (+)-neomenthol; and 11, geraniol] were investigated using three different model drugs (caffeine, hydrocortisone, triamcinolone acetonide [TA]) with varying lipophilicities. Terpenes were applied at 0.4 M in propylene glycol (PG) to mouse skin. The model drugs were applied as suspensions in PG 1 hr following enhancer pretreatment. The combination of terpenes in PG provided significant enhancement of the permeation of caffeine through mouse skin. The most active compounds 10 and 11 increased permeation by between 13-fold and 16-fold. The terpenes also enhanced the delivery of hydrocortisone, but not to as great an extent. The most active compounds 3 and 4 increased permeation between 3.9-fold and 5-fold. The compounds examined did not significantly increase the delivery of TA. The most active compound 4 only increased delivery 2.5-fold, while the next most active compound 6 only increased delivery 1.7-fold. Overall, these results indicate that the combination of terpenes with PG can significantly increase the transdermal penetration of the hydrophilic drug caffeine and the polar steroid hydrocortisone.     

Long-Term Skin Permeation Kinetics of Estradiol (I): Effect of Drug Solubilizer-Polyethylene Glycol 400

Abstract

A skin permeation cell was recently developed to overcome the deficiencies noted in the currently available in vitro diffusion cells, and to provide a cell design which is suitable for studying the long-term drug permeation kinetics through the skin and is also sensitive enough for assessing the mechanisms of skin permeation by a high performance liquid chromatography.

To evaluate the rote of drug reservoir concentration in the kinetics of skin permeation as well as to maintain a sink condition in the receptor solution, the water-miscible polyethylene glycol (PEG) 400 was incorporated into the saline solution to act as a solubilizer to enhance the aqueous solubility of the relative water-insoluble estradiol. The equilibrium solubility of estradiol at 37°C was observed to in crease exponentially as increasing the volume fraction of PEG 400 added.

The rates o f permeation of estradiol across the male and female hairless mouse, whole and stripped skins excised freshly from the abdominal region, were measured a t various PEG concentrations and the permeability coefficients were determined. The permeability co-efficients were found t o decrease as increasing the PEG concentration. A linear relationship was established between th e permeability co-efficients and the skin /solution partition coefficients and the steady-stated if fusivity was calculated. Effect of sex was assessed.

The rate of permeation and the permeability coefficient across the stratum corneum were determined, using t h e multi-laminated dif-fusional resistance model. Results demonstrated that the stratum corneum acts as the rate-limiting barrier in the skin permeation of estradiol and the incorporation of upto 40% v/v PEG 400 does not in-fluence the barrier propertiesof stratum corneum, even though PEG 400 has been found to affect the aqueous solubility, permeability co-efficient, and skin /solution partition coefficient of estradiol.     

Predicting $$\hbox {CO}_{2}$$ Solubility in Imidazole Ionic Liquids for Use in Absorption Refrigeration Systems by Using the Group Contribution Equation of State Method

Traditional absorption refrigeration such as \(\hbox {H}_{2}\hbox {O}\)–LiBr- and \(\hbox {NH}_{3}\)–\(\hbox {H}_{2}\hbox {O}\)-based refrigeration has limited applications because of several issues, including crystallization, corrosion, and large volume. \(\hbox {CO}_{2}\)–ionic liquids (ILs) as new absorption working pairs were investigated in this study. The objective was to use the group contribution equation of state (GC-EOS) method to predict the solubilities of binary systems containing high-pressure \(\hbox {CO}_{2}\)–imidazole bis(trifluoromethanesulfonimide) ILs and to investigate the applicability and accuracy of the GC-EOS model. The results showed that at pressures up to 11.0 MPa and temperatures of 273 K to 400 K, the \(\hbox {CO}_{2}\) solubility in the ILs increased with increasing system pressure but decreased with increasing temperature, and its variation rate was lower at higher pressures or temperatures. Also, \(\hbox {CO}_{2}\) solubility increased in the order of [emim][\(\hbox {Tf}_{2}\hbox {N}\)] < [bmim][\(\hbox {Tf}_{2}\hbox {N}\)] < [hmim][\(\hbox {Tf}_{2}\hbox {N}\)] < [omim][\(\hbox {Tf}_{2}\hbox {N}\)], indicating that longer alkyl chains of identical IL families resulted in higher \(\hbox {CO}_{2 }\) solubility. The model prediction of \(\hbox {CO}_{2}\) solubility in the four different ILs showed reasonable consistency with the corresponding experimental results from the literature; the largest deviation was 5.7 % for \(\hbox {CO}_{2}\)-[emim][\(\hbox {Tf}_{2}\hbox {N}\)]. Therefore, it can be concluded that the GC-EOS model is a promising theoretical solution that can be used to search for suitable \(\hbox {CO}_{2}\)–IL working pairs for absorption refrigeration systems.     

Morphology evolution of rutile particles from nanorods to microcones, again microspheres via self-assembly in Ionic Liquids (ILs) solution

Morphology evolution of rutile particles from nanorods to microcones, again microspheres were realized with the increasing of TiCl₄ via self-assembly under hydrothermal condition. A kind of ionic liquids, 1-octyl-3-methylimidazole bromide ([C₈mim]Br) was used to assist the fabrication of rutile nanostructures in the system. Characterizations of the products were performed by X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). SEM and TEM micrographs showed that the presence of [C₈mim]Br apparently resulted in the aggregation of rutile particles via self-assembly, till porous structures was formed on the surface of microspheres. Moreover, the microspheres were easy to crack when they were precipitated from solution, and the cracks can be widened under radiation of electron beam, simultaneously accompanied by the exfoliation of rutile whiskers. The corresponding mechanism of self-assembly was proposed to explain the effect of [C₈mim]Br on fabrication of these rutile nanostructures.     

Thermal Conductivities of [bmim][PF<Subscript>6</Subscript>], [hmim][PF<Subscript>6</Subscript>], and [omim][PF<Subscript>6</Subscript>] from 294 to 335 K at Pressures up to 20 MPa

Thermal conductivities are reported for a series of 1-alkyl-3-methylimidazolium hexafluorophosphates having butyl, hexyl, and octyl groups, which are expressed by [bmim][PF₆], [hmim][PF₆], and [omim][PF₆], respectively. The experimental method used was a transient short-hot-wire method. Since only a small amount of sample liquid is required, this method was found to be effective for the thermal-conductivity measurements of ionic liquids (ILs). The experimental temperatures ranged from 294 to 335 K at pressures up to 20 MPa. The values of the thermal conductivities of ILs at normal pressure are similar to those of benzene. It was found that an effect of the length of the alkyl chain on the thermal conductivities in ILs is negligible. From the data for the thermal conductivity and viscosity at 293.15 K and 0.1 MPa of ILs and normal alkanes, a simple correlation was developed based on the Mohanty theory. From comparisons between the thermal conductivities of ILs and those of organic liquids (n-hexane, benzene, and methanol), the temperature and pressure dependences of the thermal conductivity of ILs are relatively weak.     

AGET ATRP of acrylonitrile with ionic liquids as reaction medium without any additional ligand

Atom transfer radical polymerization using activators generated by electron transfer (AGET ATRP) of acrylonitrile (AN) was carried out for the first time in 1-methylimidazolium acetate ([mim][AT]), 1-methylimidazolium propionate([mim][PT]), and 1-methylimidazolium butyrate ([mim][BT]), respectively. The polymerization was approached by using ascorbic acid (VC) as a reducing agent, ethyl 2-bromoisobutyrate (EBiB) as initiator, only FeBr₃ as catalyst without any additional ligand. Kinetic studies showed that both AGET ATRP of AN in the absence of oxygen and in the presence of air proceeded in a well-controlled manner. Under the same conditions, the polymerization in the presence of air provided rather slower reaction rate and showed better control of molecular weight and its distribution than in the absence of oxygen. The sequence of the apparent polymerization rate constants of AGET ATRP of AN in three ionic liquids was k_app([mim][AT]) > k_app([mim][PT]) > k_app([mim][BT]). The living nature of the polymerization was confirmed by chain end analysis and block copolymerization of methyl methacrylate with polyacrylonitrile as macroinitiator. All the three ionic liquids and FeBr₃ could be recycled and reused and had no effect on the living nature of polymerization.     

Electrochemical methods for studying hydrogen diffusivity,permeability, and solubility in AISI 420 and AISI 430 stainless steels

Abstract

Hydrogen permeation and diffusivity were studied electrochemically at temperatures between 283 and 343 K at constant current for annealed and hardened AISI 420 and annealed AISI 430 stainless steel. Permeation rate, effective diffusivity, and solubility were calculated from these data. Annealed AISI 420 shows higher permeation rate and lower diffusivity than annealed AISI 430 stainless steel. Hardened AISI 420 has the highest permeation rate and lowest effective diffusivity. The calculation of solubility values from permeation data is in good agreement with the values obtained using a newly developed electrochemical hydrogen solubility measurement technique.

MST/1026     

Development of novel amisulpride-loaded liquid self-nanoemulsifying drug delivery systems via dual tackling of its solubility and intestinal permeability

Objective: The aim of the current investigation was at enhancing the oral biopharmaceutical behavior; solubility and intestinal permeability of amisulpride (AMS) via development of liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) containing bioenhancing excipients.

Methods: The components of L-SNEDDS were identified via solubility studies and emulsification efficiency tests, and ternary phase diagrams were constructed to identify the efficient self-emulsification regions. The formulated systems were assessed for their thermodynamic stability, globule size, self-emulsification time, optical clarity and in vitro drug release. Ex vivo evaluation using non-everted gut sac technique was adopted for uncovering the permeability enhancing effect of the formulated systems.

Results: The optimum formulations were composed of different ratios of Capryol? 90 as an oil phase, Cremophor^® RH40 as a surfactant, and Transcutol^® HP as a co-surfactant. All tested formulations were thermodynamically stable with globule sizes ranging from 13.74 to 29.19?nm and emulsification time not exceeding 1?min, indicating the formation of homogenous stable nanoemulsions. In vitro drug release showed significant enhancement from L-SNEDDS formulations compared to aqueous drug suspension. Optimized L-SNEDDS showed significantly higher intestinal permeation compared to plain drug solution with nearly 1.6–2.9 folds increase in the apparent permeability coefficient as demonstrated by the ex vivo studies.

Conclusions: The present study proved that AMS could be successfully incorporated into L-SNEDDS for improved dissolution and intestinal permeation leading to enhanced oral delivery.     

Preparation and characterization of ionic liquid intercalation compounds into layered zirconium phosphates

In this work, immobilizing a series of ionic liquids (ILs) 1-alkyl-3-methylimidazolium chloride [C _n mim]Cl (n = 2, 4, 6, 8) on the layered zirconium phosphates were investigated. [C₄mim]Cl was used to explore in detail the factors affecting intercalation. By comparing several starting materials including α-zirconium phosphate (α-ZrP), γ-zirconium phosphate (γ-ZrP) and the corresponding alkylamine preintercalated composites, it was found that the α-ZrP · 2BA (i.e., preintercalated BA were arranged in a bilayer mode at the galleries of α-ZrP) was a suitable host for intercalating ILs. Intercalation was verified with X-ray diffraction (XRD), Raman, UV–Vis and other instrumental approaches. pH effect on immobilization was investigated. Other ionic liquids including [C _n mim]Cl (n = 2, 6, 8) intercalation compounds were prepared. Based on XRD data, the interlayer distances of the studied intercalation compounds were similar, suggesting that the ionic liquids were arranged in an approximately planar manner, as confirmed by molecular modeling.     

Formulation optimization of a drug in adhesive transdermal analgesic patch

Abstract

Context: Conventional pain management approaches have limitations such as gastrointestinal side effects, frequent dosing, and difficulties in swallowing medications. Hence, to overcome these limitations, we developed a transdermal analgesic patch.

Objective: This study was designed to formulate a drug in adhesive transdermal patch with codeine (CDB) and acetaminophen (APAP) that may potentially treat moderate pain in children.

Materials and methods: Three analgesic drugs hydrocodone bitartrate, CDB and APAP were screened by a slide crystallization study using polarized light microscope and their permeation profiles were studied using vertical Franz diffusion cells across porcine ear skin, dermatomed human skin and epidermis for 24?h, and the samples were quantified by high performance liquid chromatography. Patches used for permeation studies were prepared by dissolving sub-saturation concentration of the drug(s) in adhesive (with/without 5% w/w oleic acid [OA]), cast with a film casting knife.

Results and discussion: Among the three drugs screened, CDB demonstrated the best permeation profile (660.21?µg/cm²), and shortest lag time (4.35?±?0.01?h), and hence was chosen for patch studies. The highest concentration of CDB in the patch at which drug does not crystallize was determined as 40% of its saturation solubility (Cs) and that of APAP was determined as 200% of its Cs. CDB standalone patch delivered 105.48?µg/cm² of CDB, while the CDB–APAP combination patch with 5% w/w OA delivered 151.40?µg/cm² CDB and 58.12?µg/cm² APAP in 24?h.

Conclusion: Drug-in-adhesive patches using CDB and APAP were developed for infants and children. Addition of OA enhanced solubility and permeation of drugs.     

Clinical pharmacokinetic study for the effect of glimepiride matrix tablets developed by quality by design concept

Objective: Implementation of a new pharmaceutical technique to improve aqueous solubility and thus dissolution, enhancement of drug permeation, and finally formulation of a controlled release tablet loaded with glimepiride (GLMP).

Significance: Improve GLMP bioavailability and pharmacokinetics in type II diabetic patients.

Methods: Different polymers were used to enhance aqueous GLMP solubility of which a saturated polymeric drug solution was prepared and physically adsorbed onto silica. An experimental design was employed to optimize the formulation parameters affecting the preparation of GLMP matrix tablets. A compatibility study was conducted to study components interactions. Scanning electron microscope (SEM) was performed before and after the tablets were placed in the dissolution medium. An in vivo study in human volunteers was performed with the optimized GLMP tablets, which were compared to pure and marketed drug products.

Results: Enhancement of GLMP aqueous solubility, using the polymeric drug solution technique, by more than 6–7 times when compared with the binary system. All the studied formulation factors significantly affected the studied variables. No significant interaction was detected among components. SEM illustrated the surface and inner tablet structure, and confirmed the drug release which was attributed to diffusion mechanism. The volunteer group administered the optimized GLMP tablet exhibited higher drug plasma concentration (147.4?ng/mL), longer time to reach maximum plasma concentration (4?h) and longer t_1/2 (7.236?h) compared to other groups.

Conclusions: Matrix tablet loaded with a physically modified drug form could represent a key solution for drugs with inconsistent dissolution and absorption profiles.     

Development and evaluation of topical films containing phytoestrogenic diaryheptanoids from Curcuma comosa extract

Rational: Phytoestrogens have been found to delay signs of skin aging in post-menopausal women, in a way similar to the effects of estrogens. Diarylheptanoids from a rhizome of traditional Thai herb named Curcuma comosa is considered to be a novel class of phytoestrogens.

Objectives: The aims of this study were to prepare effective topical films using mixed types and vary ratios of hydrophobic (Eudragit RL, Eudragit RS, and Eudragit NE) and hydrophilic polymer (hydroxylpropyl methycellulose, HPMC) with Transcutol as a permeation enhancer for delivery of diarylheptanoids to improve signs of skin aging in post-menopausal women.

Material and methods: Topical films were characterized for their physical and mechanical properties. In vitro release, skin permeation and accumulation were evaluated using Franz diffusion cell and the concentrations of diarylheptanoids were determined using high-performance liquid chromatography.

Results: The combined formulations between HPMC and Eudragit NE showed the satisfactory physical and mechanical properties, and also provided the highest amount of drug released compared to Eudragit RL and Eudragit RS. When the proportion of HPMC amount in the polymer matrix increased, the cumulative drug release also increased (HPMC: Eudragit NE 6:4?>?5:5?>?4:6). Moreover, they provided a high accumulation of diarylheptanoids within skin when using transcutol as a permeation enhancer.

Conclusion: The obtained data provided the skin permeation and accumulation behavior of diarylheptanoids, indicating the feasibility of a skin delivery of the C. comosa extract. The developed films might be topically used as an alternative therapy for protection of skin aging in peri and post-menopausal women.