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India is the largest exporter of menthol, a highly valued natural volatile compound obtained from peppermint. However, natural plant menthol, which often found to be adulterated. The standard methods used for quantitative analysis of menthol are not good enough to identify certain adulterants. One of the commonly used adulterants in menthol is found to be carbitol which is nothing but diethylene glycol monoethyl ether or 2-(2-Ethoxyethoxy) ethanol. This adulterant cannot be detected properly with the gas chromatography method as prescribed in the IS (Indian Standards) 3134:1992 method for this purpose. The present paper deals with the development of a method using gas chromatography with mass spectrometry (GC-MS) which is easy and simple to determine adulteration of carbitol in menthol. It has been demonstrated that by using this method developed here can easily detect the presence of carbitol in menthol at a level as low as 1 μg/mL with linearity correlation coefficient >0.999 for the concentration range of 5.0 to 100 μg/mL. This method is found to be robust and easy to adapt.

The measurement of densities (ρ) of the pure component diethylene glycol monoethyl ether (2-(2-ethoxyethoxy)ethanol) has been carried out using a vibrating-tube densimeter (Anton Paar DMA HPM) alon...

This experiment evaluated the impacts of administering a bovine appeasing substance (BAS) at feedlot entry to receiving cattle. Angus-influenced steers (n = 342) from 16 sources were purchased from an auction yard on day –1, and transported (12 hr; 4 trucks) to the feedlot. Upon arrival on day 0, shrunk body weight (BW; 240 ± 1 kg) was recorded and steers were ranked by load, shrunk BW, and source and assigned to receive BAS (IRSEA Group, Quartier Salignan, France; n = 171) or placebo (diethylene glycol monoethyl ether; CON; n = 171). The BAS is a mixture of fatty acids that replicate the composition of the bovine appeasing pheromone. Treatments (5 mL) were topically applied to each individual steer on their nuchal skin area. Steers were allocated to 1 of 24 drylot pens (12 pens/treatment) and received a free-choice diet until day 46. Steers were assessed daily for bovine respiratory disease (BRD) signs, and feed intake was recorded from each pen daily. Steer unshrunk BW was recorded on days 7, 17, 31, 45, and 46. Shrunk BW on day 0 was added an 8% shrink to represent initial BW, and final BW was calculated by averaging BW from days 45 and 46. Blood samples were collected from 5 steers/pen on days 0, 7, 11, 31, and 45. Pen was considered the experimental unit. Steer BW gain was greater (P = 0.04) in BAS vs. CON (1.01 vs. 0.86 kg/d, SEM = 0.05). Feed intake did not differ (P = 0.95) between treatments, resulting in greater (P = 0.05) feed efficiency in BAS vs. CON (171 vs. 142 g/kg, SEM = 10). Plasma cortisol concentration was greater (P = 0.05) and plasma glucose concentration was less in CON vs. BAS on day 7 (treatment × day; P = 0.07 and

Topical psoralens plus ultraviolet A radiation (PUVA) therapy consists in the topical application of 8-methoxypsoralen (8-MOP) followed by the skin irradiation with ultraviolet A radiation. The employment of classical 8-MOP vehicles in topical PUVA therapy is associated with poor skin deposition and weak skin permeability of psoralens, thus requiring frequent drug administration. The aim of the present work was to formulate solid lipid nanoparticles (SLNs) able to increase the skin permeation of 8-MOP. For this purpose, the penetration enhancer Transcutol&reg, P (TRC) was added to the SLN formulation. SLNs were characterized with respect to size, polydispersity index, zeta potential, entrapment efficiency, morphology, stability, and biocompatibility. Finally, 8-MOP skin diffusion and distribution within the skin layers was investigated using Franz cells and newborn pig skin. Freshly prepared nanoparticles showed spherical shape, mean diameters ranging between 120 and 133 nm, a fairly narrow size distribution, highly negative &zeta, potential values, and high entrapment efficiency. Empty and loaded formulations were almost stable over 30 days. In vitro penetration and permeation studies demonstrated a greater 8-MOP accumulation in each skin layer after SLN TRC 2% and TRC 4% application than that after SLN TRC 0% application. Finally, the results of experiments on 3T3 fibroblasts showed that the incorporation of TRC into SLNs could enhance the cellular uptake of nanoparticles, but it did not increase their cytotoxicity.

Simple Summary Stress is a common issue faced by ruminants throughout their productive lives, with significant effects on health and performance of the herd. Hence, strategies that alleviate stress-induced responses with a concomitant increase in performance and health are warranted. Administration of the bovine appeasing substance improved performance and reduced the costs related to pharmacological intervention of pre-weaning dairy calves. Therefore, the utilization of the bovine appeasing substance is a feasible alternative to improve health and performance of the dairy cattle herd. Abstract (1) Background: Ruminants often face stressful situations throughout their productive lives. More specifically, pre-weaning dairy calves are exposed to novel environments, feedstuffs, and pathogens that affect their health and performance. Hence, alternatives that reduce stress and promote growth of pre-weaning dairy calves are warranted. Therefore, this study evaluated the effects of biweekly bovine appeasing substance (BAS) administration on performance and disease incidence in dairy Gir × Holstein female calves prior to weaning. (2) Methods: At birth, 140 female Gir × Holstein calves were randomly assigned to receive BAS (SecureCattle; (IRSEA Group, Quartier Salignan, France; n = 70) or placebo (BAS carrier, diethylene glycol monoethyl ether; CON; n = 70) biweekly until weaning (70 days of age). Calves were allocated into individual housing at random, with no physical contact between treatments to avoid cross-contamination. Experimental treatments (5 mL) were applied topically to the nuchal skin area of each calf. Throughout the experimental period, all animals were observed daily for medical conditions (diarrhea, pneumonia, and others), medical/pharmacological interventions were recorded, and the costs related to these procedures were analyzed. Concurrently with treatment application, calves were individually weighed, and data were analyzed using animal as the experimental unit. (3) Results: Treatment × day and treatment × period (14-day interval) interactions were observed for body weight (BW) and average daily gain (ADG; p ≤ 0.05), respectively. Calves receiving BAS had greater BW at weaning (p = 0.02) and tended to have a greater BW on day 56 (p = 0.06). Similarly, ADG was greater for BAS from days 42 to 56 (p = 0.04) and tended to be greater from days 56 to weaning (p = 0.10). No differences were observed on the overall occurrence of diseases (p = 0.92), whereas the most common observed diseases were diarrhea and pneumonia. The incidence and mean age at which animals were detected with these diseases did not differ (p ≥ 0.46). Nonetheless, CON calves detected with disease had a reduced ADG vs. BAS-administered counterparts (p < 0.01). No differences were observed between disease-diagnosed BAS vs. healthy CON, but healthy BAS had a greater ADG vs. healthy CON (p = 0.03). A treatment effect was observed for the cost per head of each pharmacological intervention (p = 0.05). (4) Conclusions: In summary, BAS administration at a 14-day interval improved performance and reduced the costs of pharmacological interventions of pre-weaning Gir × Holstein dairy calves.

Topical psoralens plus ultraviolet A radiation (PUVA) therapy consists in the topical application of 8-methoxypsoralen (8-MOP) followed by the skin irradiation with ultraviolet A radiation. The employment of classical 8-MOP vehicles in topical PUVA therapy is associated with poor skin deposition and weak skin permeability of psoralens, thus requiring frequent drug administration. The aim of the present work was to formulate solid lipid nanoparticles (SLNs) able to increase the skin permeation of 8-MOP. For this purpose, the penetration enhancer Transcutol® P (TRC) was added to the SLN formulation. SLNs were characterized with respect to size, polydispersity index, zeta potential, entrapment efficiency, morphology, stability, and biocompatibility. Finally, 8-MOP skin diffusion and distribution within the skin layers was investigated using Franz cells and newborn pig skin. Freshly prepared nanoparticles showed spherical shape, mean diameters ranging between 120 and 133 nm, a fairly narrow size distribution, highly negative ζ potential values, and high entrapment efficiency. Empty and loaded formulations were almost stable over 30 days. In vitro penetration and permeation studies demonstrated a greater 8-MOP accumulation in each skin layer after SLN TRC 2% and TRC 4% application than that after SLN TRC 0% application. Finally, the results of experiments on 3T3 fibroblasts showed that the incorporation of TRC into SLNs could enhance the cellular uptake of nanoparticles, but it did not increase their cytotoxicity.

The density (ρ), speed of sound (u), and viscosity (η) of the binary mixtures of (diethylene glycol monoethyl ether (carbitol) and water, ethanol, N,N-dimethylformamide) have been measured in full concentration range at T = 288.15, 298.15, 308.15, and 318.15 K and p = 0.0868 MPa. Using the experimental data, the molar volume (Vm), excess molar volume (VmE), isentropic compressibility (κs), excess molar isentropic compressibility (κs,mE), and viscosity deviation (Δη) were calculated. The most negative values of VmE and κs,mE and positive values of Δη obtained for the carbitol + water mixture are indicative of the strong interactions between different components relative to two other systems. The values of ρ, Vm, and κs for the studied mixtures were correlated using the Jouyban–Acree model with high accuracy. Furthermore, the obtained values of VmE, κs,mE, and Δη were described by the Redlich–Kister equation and reasonable standard deviations were obtained.

A heightened interest in (trans)dermal delivery is in part driven by the need to improve the existing skin therapies and also the demand for alternative routes of administration, notably for pharmaceutical actives with undesirable oral absorption characteristics. The premise of delivering difficult actives to the skin or via the skin however is weighed down by the barrier function properties of the stratum corneum. Short of disrupting the skin by physical means, scientists have resorted to formulation with excipients known to enhance the skin penetration and permeation of drugs. A vehicle that has emerged over the years as a safe solubilizer and enhancer for a broad range of drug actives is the highly purified NF/EP grade of diethylene glycol monoethyl ether (DEGEE) commercially known as Transcutol®. Whereas numerous studies affirm its enhancing effect on drug solubilization, percutaneous absorption rate, and/or drug retention in the skin, there are few publications that unite the body of the published literature in describing the precise role and mechanisms of action for Transcutol®. In view of the current mechanistic understanding of skin barrier properties, this paper takes on a retrospective review of the published works and critically evaluates the data for potential misses due to experimental variables such as formulation design, skin model, skin hydration levels, and drug properties. The goal of this review is to mitigate the incongruence of the published works and to construct a unified, comprehensive understanding of how Transcutol® influences skin penetration and permeation. Graphical Abstract Transcutol has affinity for the hydrophilic head groups of the stratum corneum structures.

The aim of the current research was to investigate the release of diclofenac sodium, a poorly water-soluble drug from different formulations in vitro. A microemulsion (ME) was prepared using caprylocaproyl polyoxyl-8 glycerides, diethylene glycol monoethyl ether, and propylene glycol monolaurate. For enhancing the viscosity, carbopol was used to form an ME-based gel. The prepared formulations were characterized for physical appearance, droplet size, zeta potential, refractive index, percentage transmittance, heating–cooling cycles, phase separation, pH, conductivity, viscosity, drug content, staining solubility test, transmission electron microscopy and in vitro drug release using Franz diffusion cells. The mean droplets size for ME and ME-based gel-systems were 114.4 ± 0.472, and 178 ± 2.46 nm respectively, whereas the zeta potential values were −33.3 ± 0.64 mV for the former and −33.0 ± 0.40 mV for the latter. No significant variations in the pH nor physical appearance alterations were observed while stability tests were performed. Further, TEM images for drug-loaded ME and the gel exhibited nano-droplets that were spherical in shape. The release rate of diclofenac sodium formulated as ME or as ME gel had the highest release values (76.67 ± 8.63%) and (69.28 ± 7.14%) after 6 h respectively. This was statistically significant (p

Исследована фазовая диаграмма системы «сверхкритический диоксид углерода (СК-С0) - этилкарбигол (моноэтиловый эфир диэтиленгликоля)» на изотермах 308, 318 и 323 K, дополняющая имеющиеся литературные данные, и проведено их описание с использованием уравнения состояния Пенга-Робинсона и закона смешивания Мухопадхьяи и Рао. Предложен диапазон термодинамических параметров, позволяющих эффективно удалять этилкарбигол из полимеров при их пластификации и сохранять при этом растворимые в СК-С0 компоненты готового продукта., The phase diagram of the system «CO - diethylene glycol monoethyl ether (ethylcar-bitol)» was studied on isotherms 308, 318 and 323 K. The available literature data are supplemented by the results of this study. The obtained data are described using the Peng-Robinson equation of state and the Mukhopadhyaya and Rao mixing law. A range of thermodynamic parameters is proposed to effectively remove ethylcarbitol from polymers during their plasticization and to preserve the components of the finished product soluble in supercritical CO., Сверхкритические Флюиды: Теория и Практика, Выпуск 4 (4) 2020

Background: The purpose of this study was to evaluate the effect of types of surfactants and cosurfactants on physicochemical properties and permeability of sumatriptan-loaded microemulsions through rat skin. Methods: Different types of surfactants and cosurfactants were used to prepare drug-loaded microemulsions. The physicochemical characters and permeability parameters of these formulations were measured. Results: The experimental microemulsions with varying components had small droplet size ranging from 24.6 nm to 2568.8 nm, low viscosity ranging from 7.49 to 43.34 cps and significant permeation enhancement ratio ranging from 23.0 to 98.6 when compared to the control group. Conclusion: The composition and proportion of surfactants and cosurfactants were key factors for the physiochemical properties of drug-loaded microemulsions. The cumulative transdermal amount of the microemulsion containing mixture surfactant of Laureth-3/Laureth-23 was higher than that of the microemulsion with a mixture of Tween 80/Span 20. In the selected cosurfactant, diethylene glycol monoethyl ether (DEGMEE) showed highest permeation enhancement. Thermodynamic stability tests revealed that the experimental microemulsion was a stable enough formulation to be considered as a suitable carrier for sumatriptan.

Tacrolimus (TAC), a non-steroidal anti-inflammatory and immunosuppressive agent, is used for the treatment of atopic dermatitis (AD) and skin immune diseases. TAC-loaded topical hydrogel formulations composed of carbomer, carnosine, transcutol P (diethylene glycol monoethyl ether) and humectant were prepared. For comparison, TAC-loaded topical cream-type formulations were also prepared and commercially available TAC ointment was used as a reference. A drug release study in vitro revealed that the total amount of TAC released from hydrogels over 24 h was approximately 30 times greater than that for the reference formulation. Compared to the reference ointment and creams, carbomer gel formulations showed higher skin permeation and retention of TAC (significantly different at p 0.05), especially those with more than 10% of transcutol P. Therefore, carbomer gel formulations with sufficient levels of transcutol P are good candidates for skin delivery of TAC and have potential as therapeutic agents for the treatment of AD or immune skin disorders.

Temperature dependent solubility data of tadalafil (TDL) in diethylene glycol monoethyl ether (Transcutol) + water co-solvent mixtures are not available in literature. Therefore, the aim of present study was to determine the temperature dependent solubility data of crystalline TDL in mono-solvents and various Transcutol + water co-solvent mixtures from 298.15 to 333.15 K at atmospheric pressure. The experimental solubilities of crystalline TDL were measured using the shake flask method. The experimental solubilities were correlated with the Apelblat model. The solubilities of crystalline TDL were regressed by Apelblat equation with a relative deviation in the range of 0.02 to 6.81% in all co-solvent mixtures investigated at 298.15 to 333.15 K. The root mean square deviations were observed in the range of 0.013 to 0.058. However, the correlation coefficients were observed in the range of 0.996 to 0.999. The solubility of crystalline TDL was found to be increased with increase in temperature and mass fraction of Transcutol in co-solvent mixtures. The mole fraction solubility of crystalline TDL was observed highest in pure Transcutol (8.76 × 10− 3 at 298.15 K) as compared to water (5.74 × 10− 7 at 298.15 K). Around 15,263 fold enhancements in solubility of crystalline TDL in Transcutol were observed as compared to its aqueous solubility at 298.15 K. The dissolution of TDL in most of the co-solvent mixtures was assumed to be non-spontaneous, endothermic and an entropy driven process. Overall, the results of these studies indicated that Transcutol could be used as a co-solvent in formulation development especially in terms of liquid dosage forms of crystalline TDL.

The solubility of N-(4-chlorophenyl)-2-(pyridin-4-ylcarbonyl)hydrazinecarbothioamide (isoniazid analogue) in various diethylene glycol monoethyl ether (Transcutol) + water cosolvent mixtures was measured at (298.15 to 338.15) K using the shake flask method. In order to investigate the influence of temperature on solubility, the experimental solubilities of the isoniazid analogue were correlated with the Apelblat equation. To investigate the influence of cosolvent mixtures on solubility, the log–linear model of Yalkowsky was used. For the Apelblat equation, the root-mean-square deviations (RMSDs) were observed in the range of 0.004 to 0.033. For the Yalkowsky model, the RMSDs were observed in the range of 0.021 to 0.114. The correlation coefficients were observed in the range of 0.996 to 0.999. These results indicated the good fitting of experimental solubilities with the Apelblat equation and Yalkowsky model. The solubility of isoniazid analogue was found to be highest and lowest in pure Transcutol (4.23·...

The solubilization behavior of paracetamol (PCT) in a diethylene glycol monoethyl ether (Transcutol)–water mixture at (298.15 to 333.15) K is not reported in literature so far. Therefore, attempts were made to investigate the solubilization behavior of PCT in monosolvents and various Transcutol–water mixtures at the temperature range of (298.15 to 333.15) K. The mole fraction solubility of PCT was determined by reported shake flask method. The experimental solubility data of PCT in monosolvents and various Transcutol–water mixtures were found to be correlated well with the modified Apelblat model with the correlation coefficients in the range of 0.996 to 0.999. The solubility of PCT was found to be increased significantly with the increase in temperature and mass fraction of Transcutol. The mole fraction solubility of PCT was found to be highest in pure Transcutol (0.111 at 298.15 K) as compared to water and other cosolvent mixtures. The positive values of enthalpies and entropies indicated that the disso...

Summary Background The solvent diethylene glycol monoethyl ether (DEGEE) is currently used in over 500 cosmetic products and has enabled the formulation of a topical 5% dapsone gel for the treatment of acne. It is anticipated that this common cosmetic ingredient will be a component in numerous future prescription topical products approved for the US market. Dermatologists are already treating patients that apply products containing 5–40% of this solvent multiple times each day. Aims To provide dermatologists a review of this solvent’s safety and tolerance in addition to describing how it interacts with the stratum corneum, sebum, and resident microflora. Methods To critically review technical and patent literature that provides insight into this novel solvent. Results Diethylene glycol monoethyl ether when used in a 99.9+% pure pharmaceutical grade is safe and well tolerated. Up to half of the applied solvent crosses the skin’s barrier and becomes systemic. For certain drug actives, this solvent provides for an intracutaneous depot. This solvent has not demonstrated any inherent antimicrobial properties but was found to be mildly inhibitory toward Propionibacterium acnes. Conclusions This safe, well-tolerated solvent is already used in many cosmetics and will become an ingredient in an increasing number of prescription products. Its ability to modify the skin delivery of actives it is formulated with (or formulation components that are applied just shortly before or after) make it important for dermatologists to have an understanding of this emerging solvent.

A simple gas chromatography–flame ionisation method was initially developed for the simultaneous determination of the prohibited flavours, namely diethylene glycol (DEG), diethylene glycol monoethyl ether (DEGME) and coumarin in food samples. The analytes were extracted using methanol, and was sonicated for 10 min. The extracts were filtered and directly injected into the GC unit that was fitted with a capillary AT TM -AQUAWAX column. Caffeine, which was found in some of the soft drink samples were also successfully separated. Excellent separation of these flavours and caffeine was achieved in about 23 min. Limit of detection, linear range, and reproducibility of the retention time were evaluated. Average recoveries in the ranges of 93.44–97.54% (RSD, 2.68%) for DEGME, 92.99–101.45% (RSD, 2.99%) for DEG, 90.64–100.00% (RSD, 1.99%) for coumarin and 94.62–97.50% (RSD, 2.54%) for caffeine were obtained. None of the food items analysed was found to contain coumarin, DEG or DEGME. However, of the 35 soft drinks and fruit juices that were analysed, eleven samples were found to contain caffeine, but only one exceeded the legal limit.

Densities and viscosities were measured as a function of composition for binary liquid mixture of diethylene glycol monoethyl ether [CH 3 CH 2 O(CH 2 ) 2 O(CH 2 ) 2 OH] + water from 293.15 to 333.15 K at atmospheric pressure, with a capillary pycnometer and Ubbelohde capillary viscometer respectively. From the experimental data, the excess molar volume V E , viscosity deviation Δη, and the excess energy of activation for viscous flow Δ G *E were calculated. These data were correlated by the Redlich-Kister type equations to obtain the coefficients and standard deviations. The results showed a strong molecular interaction between diethylene glycol monoethyl ether and water.

Transcutol® or diethylene glycol monoethyl ether is a liquid which has a long history of use in cosmetic and over-the-counter topically applied products. Transcutol® has been applied in several commercial preparations and is used in many studies as the main ingredient of formulations. It has been used in formulations as a co-surfactant and a penetration enhancer. It is frequently utilized in topical formulations (dermal drug delivery systems), transdermal delivery systems, and ocular and also intranasal delivery systems. It is also used as an ingredient in nanoemulsions, sunless tanning products, and in a wide range of hair-coloring products which are rinse-off products. This solvent will be a key component of many cosmetic products as well as dermatics in foreseeable future. In this chapter, some of the most important physicochemical properties of Transcutol® will be reviewed, as well as its application, pharmacology, and biomedical effects and toxicity.

The rate of Transcutol® (TC)-water interchange, was studied using whole and stripped hairless rat skin in a modified vertical Franz diffusion cell. The presence of stratum corneum limited the passage of the two solvents, but after stripping of the skin, the rate of TC transfer increased and the water flow rose until the vapour pressure at the skin surface and in the ambient air was similar. The results suggest that TC increased the donor hydration by increasing the outflow of water, with a change in the donor composition. These two opposite fluxes and the alteration of the bulk constitution of the skin and of the donor compartment throughout the experiment, are important factors to be considered for the permeation studies with this solvent.

Dermal exposure to chemicals is highly relevant in relation to the use of cosmetic products, both in consumers and in individuals exposed occupationally. Regulatory frameworks exist within the EU to limit the dermal exposure of the general population and workers to chemicals in general, as well as to limit the use of certain substances in cosmetic products. The objective of the study was to investigate and compare toxicological evaluations of dermal exposure performed under current regulatory frameworks. The publicly disseminated hazard information under the respective regulatory frameworks was compiled and compared for the five substances resorcinol, p-phenylenediamine, p-aminophenol, N-phenyl-p-phenylenediamine, and diethylene glycol monoethyl ether. A low consistency between evaluations was observed in respect to data coverage and cited dose descriptors. No systematic differences over all five substances were identified from the viewpoint of dermal hazard assessment. The critical effect and corresponding systemic effect dose descriptor was identical for two substances, differed somewhat for two other (a factor of 2-2.5). For N-phenyl-p-phenylenediamine a critical effect was only identified under REACH. QC 20140310

In order to achieve fast release of ibuprofen, a slightly soluble model substance (0.52×10?4 mol/l), surfactant systems for oral use with different PEG-40 hydrogenated castor oil (C)/diethylene glycol monoethyl ether (T) ratios were investigated. Comparison between dissolution profiles for ibuprofen from formulated systems and from two commercial products, film tablets and soft capsules, is presented in this paper. Photon correlation spectroscopy has shown that after high dilution with water, the surfactant systems were able to form micellar solutions. The size of micelles varied from 14.8±0.075 nm to 16.2±0.021 nm with increasing C/T ratio from 1:2 to 2:1. Although increasing content of PEG-40 hydrogenated castor oil resulted in formation of larger micelles, the lower values of polydispersity index indicated that a more homogeneous distribution of micelle sizes was gained. Conductometric analysis had demonstrated that the system composing of C/T ratio 2:1 showed the most pronounced interaction between droplets, which can be seen as a high rise of electrical conductivity with increasing water content (wwater/wtotal) in the sample. No significant difference in percolation threshold between formulations with different C/T ratios was observed. Different surfactant systems were adsorbed on magnesium aluminometasilicate, as adsorbent with high specific active surface (≈300 m2/g), in order to investigate the potential influence of adsorbent on ibuprofen dissolution rate. Formulated systems, with or without adsorbent, were filled in hard gelatin capsules. The dissolution profiles of ibuprofen from different formulations were obtained in 30 min by dissolution apparatus with rotating baskets and compared with dissolution profiles of ibuprofen from commercial products. For formulations without adsorbent faster release of ibuprofen in the first minutes of the dissolution test, showed formulations with C/T ratio 2:1 and 1:1. Magnesium aluminometasilicate, as adsorbent with high specific surface area, significantly improved release rate of ibuprofen from formulation with C/T ratio 2:1. However, for the formulation with C/T ratio 1:1, significantly lower release of ibuprofen was observed. Formulations with other C/T ratios in terms of fast ibuprofen release did not give satisfying results. The obtained results show that in comparison to dissolution profile of ibuprofen from commercial products proper C/T ratio as well as magnesium aluminometasilicate, as adsorbent with high specific surface area, can significantly increase release of ibuprofen. U radu je prikazana izrada različitih PEG-40 hidrogenizovano ricinusovo ulje (C)/dietil-englikolmonoetiletar (T) surfaktantnih sistema za peroralnu primenu, radi postizanja bržeg rastvaranja ibuprofena u odnosu na komercijalne preparate tipa film tableta i mekih želatinskih kapsula. Surfaktantni sistemi sa C/T odnosom 1:2, 2:1 i 1:1 okarakterisani su ispitivanjem promene električne provodljivosti sistema sa promenom sadržaja vode (% (mvode/ /mukupno)), kao i merenjem veličine prečnika kapi pri sadržaju vode od 95% (mvode/mukupno). Formulacije C/T odnosa 2:1 i 1:1 pokazale su brže rastvaranje ibuprofena u odnosu na komercijalni preparat. Izrađene formulacije C/T sistema sa ibuprofenom su zatim adsorbovane na magnezijum-aluminijum-metasilikatu, koji kao adsorbens velike specifične aktivne površine, znatno ubrzava rastvaranje ibuprofena pri C/T odnosu 2:1, dok pri drugim C/T odnosima, pozitivan uticaj adsorbensa na brzinu rastvaranja ibuprofena izostaje. Pravilnim odabirom odnosa lekovita supstanca/surfaktant/kosurfaktant/adsorbens, moguće je postići brzo rastvaranje teško rastvorljive lekovite supstance iz čvrstih farmaceutskih oblika.

To study health effects in hospital cleaners (N = 21) at floor polish removal and application. The cleaners were investigated before exposure (Monday = day 1), after polish removal work (day 2), and after application of floor polish (day 3). Ratings of symptoms, tear-film break-up-time (BUT), nasal patency and biomarkers in nasal lavage were studied. There was a significant increase both day 2 and day 3, as compared to pre-exposure, in ocular, nasal, throat symptoms, solvent smell, dyspnoea, and general symptoms such as headache and fatigue. Posterior nasal patency was decreased day 2 (p < 0.01) and day 3 (p < 0.01). No change of nasal biomarkers (ECP, MPO, lysozyme, albumin) was seen. BUT was decreased after polish removal (p < 0.01), but not after polish application. Separate test of the weekday effect in non-exposed showed slight improvements, or no change of symptoms or clinical signs from Monday to Wednesday. Air concentrations of ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monoethyl ether, dipropylene glycol monomethyl ether, diethylene glycol monoethyl ether and ethylene glycol phenyl ether 103, 666, 13,650, 7,000, 67, and 27 mu g/m(3), respectively, at polish application. Glycol ether levels were reduced to 3% after 2 days and 0.3% after 17 days. Emissions from a common water-based polish remover and floor polish system may cause ocular and airway irritation and general symptoms, and reduce tear-film stability and nasal patency. The levels of glycol ethers had a rapid decay.

In this study the effect of 2 penetration modifiers, dimethyl isosorbide (DMI) and diethylene glycol monoethyl ether (DGME) on the skin delivery of hydroquinone (HQ), salicylic acid (SA) and octadecenedioic acid (DIOIC) was investigated. Ten percent DMI and DGME were separately formulated into oil-in-water emulsions containing 1.8% HQ, SA and DIOIC, respectively. Skin delivery and the flux across split-thickness human skin of the active ingredients were determined using Franz diffusion cells. An emulsion with 10% water incorporated instead of the water-soluble penetration modifiers served as a control. The study showed that neither 10% DMI nor 10% DGME significantly enhanced the skin permeation of the various lipophilic active ingredients or the uptake into the skin. It was hypothesized that the addition of the penetration modifiers to the emulsions not only enhanced the solubility of the various active ingredients in the skin but also in the formulation, resulting in a reduced thermodynamic activity and hence a weaker driving force for penetration. Therefore, the effect of DMI and DGME on the solubility of the active ingredients in the skin was counteracted by a simultaneous reduction in the thermodynamic activity in the formulation.

The time of erythema onset may be used as a response parameter for quantification of the cutaneous erythema response induced by methyl nicotinate. The vehicles light mineral oil (LMO; test) and medium chain triglycerides (MCT; standard) were compared with regard to the pharmacodynamic response. Moreover, the influence of penetration enhancers on the time of erythema onset was investigated under zero order penetration kinetics. The enhancers dimethyl sulfoxide, diethylene glycol monoethyl ether and three different glycerides in different concentrations were added to MCT as a standard vehicle. All preparations were applied to the forearms of volunteers under infinite dose conditions at different thermodynamic drug activity levels (0.2–3.2% of the saturation level) and different drug concentrations (0.051–0.816%), respectively. Different penetration kinetics do not influence data of erythema onset, as these data are comparable to those obtained under finite dose conditions (first order penetration kinetics). With regard to the penetration enhancers, a significantly enhanced penetration of methyl nicotinate could be observed only for diethylene glycol monoethyl ether and dimethyl sulfoxide. However, no significant difference between light mineral oil and MCT could be found with regard to penetration enhancement. The time of erythema onset is an easy and efficient parameter for quantification of the pharmacodynamic response caused by nicotinates.

The purpose of this study was to scale up an oil/water (o/w) cream formulation containing 40% diethylene glycol monoethyl ether (DGME), developed via 300-g laboratory batches in a 2(5-2) fractional factorial design, to 7-kg batch sizes in a Brogli-10 homogenizer. The o/w cream was manufactured via a standard phase-inversion process in the Brogli-10 homogenizer. Partitioning studies of DGME were conducted in test tubes at ambient temperature and after 24 hr at 70 degrees C in a convection oven. Phase height was measured by vernier calipers. Microscopy studies of excipients with and without treatment with water or a DGME/water mixture were conducted with a Nikon microscope after equilibration at 35 degrees C for 24 hr. During creation of the 7-kg pilot-scale batches, congealed material was observed between the sweep agitation blade and the discharge port, where the Brogli-10 homogenizer is not temperature jacketed. Factors that increased the amount of congealed material were higher temperatures during primary emulsification and longer cooling times. Partitioning studies revealed that DGME resides in the aqueous external phase of this formulation. Microscopy studies revealed that DGME in the external phase of this cream has a profound impact on the solubility of certain solid, waxy excipients (e.g., cetyl alcohol and polyoxyethylene-2-stearyl ether) at 35 degrees C. From this study, it appears that DGME resides in the external phase of the o/w cream. During manufacturing, it is hypothesized that the presence of DGME in the external phase alters the solubility of certain solid, waxy excipients in the formula such that they no longer primarily reside in the internal oil phase. On cooling, these materials precipitate or congeal in the external phase. The fractional factorial experimental design at the 300-g laboratory scale did not predict the issues encountered during scale-up. Differences between laboratory scale and pilot plant scale that explain why this phenomenon was not seen during laboratory scale are differences in cooling times, nonjacketed or "cold spots" in the Brogli-10 homogenizer, and a low proportion of congealed material in relation to the total batch size (1.5%).

The effect of diethylene glycol monoethyl ether (DGME; Transcutol) on the permeation of ivermectin, a broad-spectrum antiparasitic agent, through bovine skin was evaluated by in vitro permeation experiments followed by serial sectioning of the skin to assess the amount of ivermectin retained in the skin. Ivermectin permeation through bovine skin was enhanced by DGME and this enhancement was DGME-concentration-dependent. Permeation of ivermectin was effectively enhanced in vehicles with low proportions of DGME, but the magnitude of permeation enhancement decreased as the proportion of DGME increased. The permeation was accompanied by the formation of cutaneous depots of ivermectin. Furthermore, the data indicated that the flux and the cutaneous accumulation of ivermectin were sensitive to the concentration gradient of DGME across the skin. This suggested that ivermectin was permeating with DGME, in which it is very soluble. Hence, the enhancing mechanism involves solubilization of the ivermectin by DGME and the transport of DGME itself across the skin. Based on these results, DGME appears to be a potential vehicle for topical delivery of ivermectin by transport through the skin and through formation of cutaneous depots of ivermectin.

The use of diethylene glycol monoethyl ether as a flavor solvent is restricted. Since existing methods of quantitation are tedious or require sophisticated multi-dimensional GC instrumentation, a simple method has been developed using low cost GC-MS. Monitoring of ions 31 and 45 enables quantitation of DEGEE in essential oils at levels down to 1 μg/g with accuracy equal to or better than 15%.

A simple GC method with a capillary column was developed for simultaneous determina tion of 6 carrier solvents (ethanol, propylene glycol, glycerin, triacetin, diethylene glycol monoethyl ether and 1, 3-butylene glycol) in flavor preparations. Samples were diluted with n-propanol, and 1μL aliquots were injected into a GC apparatus. No further treatments were carried out to remove interfering substances. Out of 96 flavor preparations, ethanol was found in 68, propylene glycol in 31, glycerin in 18, and triacetin in 12.

A short-term study involving dietary administration of 0·0, 0·25, 1·0 and 5·0% diethylene glycol monoethyl ether (DGME) to rats for 90 days has been carried out on a commercial sample of DGME containing 0·4% ethylene glycol as an impurity. The animals remained healthy throughout the test. There was one death, that of a male in the 5% group. The growth of both sexes of rats was significantly retarded at the 5% level and was accompanied by a fall in food consumption. No haematological changes were observed at any dietary level. There was evidence of slightly impaired renal function at the highest dietary level, notably in males. The organ weight findings having toxicological significance were increases at the 5% level in the relative weights of the kidney (both sexes) and testes. Pathological examination revealed significant changes at the 5% level and consisted of hydropic degeneration of kidney tubules, fatty change in the liver and testicular oedema. A no-effect level has been established of 1% DGME in the diet of rats for 90 days. On the basis of the results obtained it is suggested that DGME of the necessary degree of purity is acceptable for use as an intentional food additive.