Abstract: The purpose of the present study was to examine and compare the cosolvency using three different cosolvents, namely PEG 400, PG, and glycerin on the aqueous solubility enhancement of a poorly aqueous soluble drug, etoricoxib, since solubilization of nonpolar drugs constitutes one of the important tasks in the formulation design of liquid dosage forms. The aqueous solubility of etoricoxib was 0 . 0 7 6 7 ± 0 . 0 0 1 8 mg/mL, which was significantly improved by the addition of PEG 400, PG, and glycerin as cosolvents. It was scrutinized that the less-polar solvents were found to increase the aqueous solubility by greater extent, thus accentuating hydrophobic interaction mechanism. Among various solvent-cosolvent blends investigated, water-PEG 400 showed highest solubilization potential. Thus, the study generated an important array of data to compare the effect of these cosolvents on the aqueous solubility of etoricoxib.

Abstract: In this study, abundant naturally occurring agarose has been used as a support and ligand for palladium nanoparticles. In the presence of this catalytic system, Mizoroki–Heck and Sonogashira–Hagihara coupling reactions were performed successfully. The catalyst exhibits high activity in Mizoroki–Heck reaction under phosphane and solvent-free conditions for the reaction of iodo- and bromoarenes with butyl acrylate and styrene. This catalytic system also showed high catalytic activity for Sonogashira–Hagihara coupling reaction of various aryl halides (I, Br, Cl) under copper and ligand-free conditions in polyethylene glycol (PEG 400) as an ecofriendly and non-poisonous media. The catalyst can be separated from the reaction mixture and reused for the similar batches of the reaction. High efficiency of the catalyst along with its recycling ability and the rather low Pd-loading which are demonstrated in both Mizoroki–Heck and Sonogashira–Hagihara reactions are the merits of the presented catalyst system.

Abstract: Gold(III) chloride (HAuCl 4 ·3H 2 O) in PEG 400 was found to be an efficient catalytic system for the synthesis of biologically important functionalized spirochromene derivatives via one-pot three-component reaction of isatins/acenaphthoquinone, active methylene compounds and cyclic 1,3-diketones/4-hydroxycoumarin. A new catalytic system, recyclability of reaction medium, little reaction times and excellent yields with easy workup render this protocol more attractive and economically viable.

Abstract: Molar volumes and excess molar volumes were investigated from density values for (PEG 400 + water) and (PEG 400 + ethanol) binary mixtures at temperatures from 283.15 K to 313.15 K. Both systems exhibit negative excess volumes probably due to increased interactions like hydrogen bonding and/or large differences in molar volumes of components. Volume thermal expansion coefficients were also calculated for binary mixtures and pure solvents. The Jouyban-Acree model was used for density and molar volume correlations of the studied mixtures at different temperatures. The mean relative deviations between experimental and calculated density data were 0.1 and 0.5 %, for aqueous and ethanolic mixtures, respectively; whereas, in molar volume data the values were 18.0 and 6.9 %, for aqueous and ethanolic mixtures, respectively. The trained versions of the model for PEG 400 binary solvents could be used to predict the density values of other PEGs with reasonable prediction error employing the density of mono-solvents.

Abstract: Background Increased intestinal permeability is an important measure of disease activity and prognosis. Currently, many permeability tests are available and no consensus has been reached as to which test is most suitable. The aim of this study was to compare urinary probe excretion and accuracy of a polyethylene glycol (PEG) assay and dual sugar assay in a double-blinded crossover study to evaluate probe excretion and the accuracy of both tests. Methods Gastrointestinal permeability was measured in nine volunteers using PEG 400, PEG 1500, and PEG 3350 or lactulose-rhamnose. On 4 separate days, permeability was analyzed after oral intake of placebo or indomethacin, a drug known to increase intestinal permeability. Plasma intestinal fatty acid binding protein and calprotectin levels were determined to verify compromised intestinal integrity after indomethacin consumption. Urinary samples were collected at baseline, hourly up to 5 hours after probe intake, and between 5 and 24 hours. Urinary excretion of PEG and sugars was determined using high-pressure liquid chromatography-evaporative light scattering detection and liquid chromatography-mass spectrometry, respectively. Results Intake of indomethacin increased plasma intestinal fatty acid-binding protein and calprotectin levels, reflecting loss of intestinal integrity and inflammation. In this state of indomethacin-induced gastrointestinal compromise, urinary excretion of the three PEG probes and lactulose increased compared with placebo. Urinary PEG 400 excretion, the PEG 3350/PEG 400 ratio, and the lactulose/rhamnose ratio could accurately detect indomethacin-induced increases in gastrointestinal permeability, especially within 2 hours of probe intake. Conclusion Hourly urinary excretion and diagnostic accuracy of PEG and sugar probes show high concordance for detection of indomethacin-induced increases in gastrointestinal permeability. This comparative study improves our knowledge of permeability analysis in man by providing a clear overview of both tests and demonstrates equivalent performance in the current setting.

Abstract: The main objective this study is to prepare and evaluate the selfnanoemulsifying drug delivery (SNEDDS) system in order to achieve a better dissolution rate of a poorly water soluble drug valsartan. The present research work describes a SNEDDS of valsartan using labrasol, Tween 20 and Polyethylene glycol (PEG) 400. The pseudo-ternary phase diagrams with presence and absence of drug were plotted to check for the emulsification range and also to evaluate the effect of valsartan on the emulsification behavior of the phases. The mixtures consisting of oil (labrasol ) with surfactant (tween20), co-surfactant (PEG 400) were found to be optimum formulations. Prepared formulations were evaluated for its particle size distribution, nanoemulsifying properties, robustness to dilution, self emulsication time, turbidity measurement, drug content and in-vitro dissolution. The optimized formulations are further evaluated for heating cooling cycle, centrifugation studies, freeze thaw cycling, particle size distribution and zeta potential were carried out to confirm the stability of the formed SNEDDS formulations. The prepared formulation has a significant improvement in terms of the drug solubility as compared with marketed tablet and pure drug, thus, this greater dissolution of valsartan from formulations could lead to higher absorption and higher oral bioavailability.

Abstract: A simple and convenient approach for the synthesis of tetraheterocyclic benzothiazolo-[2,3-b]-quinazolin-1-ones has been developed utilizing the MCR methodology, which involves the condensation of 2-aminobenzothiazole, cyclic β-diketones and various aldehydes using Amberlyst-15® in PEG 400 as an environmentally benign and reusable catalyst system. Environmental benignity, recyclability, cost-effectiveness, easy workup and excellent yields are the major attributes of this one-pot procedure.

Abstract: The present work investigates the feasibility of the design of an enteric coated microporous osmotic pump tablet (ECMOPT) to prolong the drug release of an antipsychotic drug, quetiapine fumarate (QTF). The ECMOPT consisted of an osmotic core coated with a microporous membrane (MPM) made up of cellulose acetate and PEG 4000 as in situ micropore former. The effect of formulation variables such as concentration of sodium chloride, types of pore former (PEG 400, PEG 4000 and PEG 6000), coat thickness (100 and 200 microm) of MPM were evaluated for drug release characteristics. The FTIR, DSC and XRD analyses were carried out to characterize physico-chemical changes of powder blend and final formulation. SEM images have confirmed in situ micropores formation in MPM. A zero order release was obtained for QTF. The formulations were found to be stable up to 3 months when tested for stability at 40 degrees C/75% RH.

Abstract: Polyethylene glycol is found to be a nontoxic and recyclable reaction medium for the microwave-assisted, multi-component one-pot reactions of aromatic aldehydes with ethyl-2-cyanoacetate and 1,3-cyclohexanedione or 5,5- dimethyl-1,3-cyclohexanedione in the presence of piperidine. This environmentally friendly microwave protocol offers ease of operation and enables recyclability of reaction medium and synthesis of a variety of substituted tetrahydrobenzo[b]pyran derivatives. It is an efficient, promising, and green synthetic strategy to construct tetrahydrobenzo[b]pyran skeleton.

Abstract: Celecoxib, a diaryl substituted pyrazole, is practically insoluble in water which precludes its use in parenteral and liquid dosage forms. This study explores the solubility enhancement of celecoxib using hydrotropy and cosolvency solubilization approaches. The equilibrium solubility studies were performed using hydrotropes piperazine, sodium citrate, and urea and cosolvents PEG 200, PEG 400, PEG 600, DMA, Ethanol and Propylene glycol at various temperatures. Parenteral formulations using hydrotrope and cosolvents were developed and studied for accelerated stability study. The solubility of celecoxib was found to increase upto 45 times in 3M piperazine solution and upto 10232 times in PEG 600 at 25±2 0 C. The results of solubilization study showed that the increase in solubility of celecoxib is smaller in piperazine and urea when used alone as compared to the increase in solubility which was found when these hydrotropes were used in combination with cosolvents PEG 600, PEG 400, DMA and Eth. Stability studies indicated that all the formulations stored were found to be stable for drug content, pH and change in physical appearance i.e. color, precipitation.

Abstract: The synthesis of substituted quinolines can be easily and greenly accomplished by the direct reaction between the corresponding aminoalcohol and ketone using PEG-400 as reaction medium in the presence of a base, without any transition-metal catalyst.

Abstract: The aim of present work deals with formulation and characterization of atenolol fast dissolving films. Atenolol is a β – selective adrenergic antagonist used as antihypertensive agen. Films were formulated using film forming polymer like Hydroxypropylmethylcellulose (HPMC E5)(F1 – F8) and tween 80 is added to the formulation from F5 – F8 by solvent casting technique with the help of Polyethylene glycol (PEG 400) as a plasticizer and glycerine as a sweetening agent. FT-IR analysis was performed to study the interaction between the drug and polymer .The films were evaluated for weight variation, surface pH , folding endurance , drug content , dissolving time , disintegration time, in-vitro dissolution studies. Based on the evaluation parameters F4 containing Drug: Polymer (1:4) ratio showed optimum performance and marked increase in releasing of drug 92.34%, though F8 formulation has maxmimum drug release as it has less tensile strength. It can be concluded in the study that mouth dissolving film can be potential novel drug dosage form for poorly water soluble drugs.

Abstract: Based on an elementary osmotic pump, controlled release systems of diclofenac sodium (DS) were designed to deliver the drug in a zero-order release pattern. Osmotic pump tablets containing 100 mg DS were prepared and coated with either semipermeable (SPM) or microporous (PM) membranes. The tablet coats were composed of hydrophobic triacetin (TA) or hydrophilic polyethylene glycol 400 (PEG 400) incorporated in cellulose acetate (CA) solution, for SPM and PM, respectively. Variable tablet core compositions such as swelling polymers (PEO and HPMC) and osmotic agents (lactose, NaCl, and KCl) were studied. An optimized, sensitive and well controlled in vitro release design, based on the flow-through cell (FTC), was utilized to discriminate between preparations. The results revealed that the presence of PEG 400 in the coating membrane accelerated the drug release rate, while TA suppressed the release rate of DS. In the case of SPM, the amount of DS released was inversely proportional to the membrane thickness, where 5% (w/w) weight gain gave a higher DS release rate than 10% (w/w). Results of different tablet core compositions revealed that the release rate of DS decreased as PEO molecular weight increased. HPMC K15M showed the lowest DS release rate. The presence of lactose, KCl, or NaCl pronouncedly affected DS release rate depending on polymer type in the core. Scanning electron microscopy (SEM) confirmed formation of pores in the membrane that accounts for faster DS release rate. These results revealed that DS could be formulated as an osmotic pump system with a prolonged, zero-order release pattern.

Abstract: Summary: Polymers derived from cyclodextrins show several biomedical applications. In this paper, six cross-linked polyurethane networks based on β-cyclodextrin (βCD) or hydroxypropyl-β-cyclodextrin (HPβCD) and polyethylene glycols (PEG 400, PEG 1500 or PEG 4000) were synthesized by the usual two-step polymerization method. The polymers were characterized by Fourier-transformed infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA) and X-ray diffraction (XRD). The inclusion capacity was evaluated by the discoloration method of a phenolphthalein solution. In order to explore their potential use as controlled drug delivery systems, dissolution profiles and release behavior of inclusion complexes between PUR/TDI/βCD/PEG4000 or PUR/TDI/HPβCD/PEG1500 and nifedipine (NIF) were investigated. FTIR assignments confirmed the formation of urethane linkages. XRD patterns revealed that the crystallinity decreased mainly due to the crosslinking process. TGA showed three stages of mass loss attributed to water loss, cleavage of urethane bonds and volatilization of decomposition products. The inclusion capacity of cyclodextrins cross-linked with polyurethane was suitably maintained. Dissolution profiles demonstrated that the inclusion complexes PUR/TDI/βCD/PEG4000-NIF and PUR/TDI/HPβCD/PEG1500-NIF are feasible systems for controlling drug release, showing a biexponential release behavior.

Abstract: – A facile synthesis of hitherto unreported (9-methyl-9 H -carbazole- 3,6-diyl)bis(benzofuran-2-yl-methanone)s ( 3a-f ) is described, featuring the PEG-400-promoted and ultrasound-assisted Rap-Stoermer reaction of 3,6-dichloroacetyl-9-methyl-9 H -carbazole (1 ) with a variety of salicylaldehydes as well as 2-hydroxy-1-naphthaldehyde ( 2 ) in the presence of K 2 CO 3 as the base in acetonitrile. This procedure offers easy access to benzofuran-2-yl(carbazolyl)- methanone derivatives in short reaction time and the products are achieved in good yields.

Abstract: To avoid the systemic adverse effects that might occur after oral administration, transdermal delivery of ambroxol was studied as a method for maintaining proper blood levels for an extended period. Release of ambroxol according to concentration and temperature was determined, and permeation of drug through rat skin was studied using two chamber-diffusion cells. The solubility according to PEG 400 volume fraction was highest at 40% PEG 400. The rate of drug release from the EVA matrix increased with increased temperature and drug loading doses. A linear relationship existed between the release rate and the square root of loading rate. The activation energy (Ea) was measured from the slope of the plot of log P versus 1000/T and was found to be 10.71, 10.39, 10.33 and 9.87 kcal/mol for 2, 3, 4 and 5% loading dose from the EVA matrix, respectively. To increase the permeation rate of ambroxol across rat skin from the EVA matrix, various penetration enhancers such as fatty acids (saturated, unsaturated), propylene glycols, glycerides, pyrrolidones, and non-ionic surfactants were used. The enhancing effects of the incorporated enhancers on the skin permeation of ambroxol were evaluated using Franz diffusion cells fitted with intact excised rat skin at 37° using 40% PEG 400 solution as a receptor medium. Among the enhancers used, polyoxyethylene-2-oleyl ether increased the permeation rate by 4.25-fold. In conclusion, EVA matrix containing plasticizer and permeation enhancer could be developed for enhanced transdermal delivery of ambroxol.