Control of thermo reversible gelation of methylcellulose using polyethylene glycol and sodium chloride for sustained delivery of ophthalmic drug

The effect of molecular weight of polyethyleneglycol (PEG) and sodium chloride (NaCl) on the gelation temperature of methylcellulose (MC) was studied with the objective to develop a MC based formulation for sustained delivery of ophthalmic drug. The gelation temperature of 1% MC was 60 ± 0.40°C. It was found that the gelation temperature of MC was reduced with the addition of 10% PEG and extent of reduction of gelation temperature was depended on the molecular weight of PEG at same PEG concentration of 10%. The gelation temperature of MC was reduced by 10.4 to 5.9°C with the increasing molecular weight of PEG starting from 400 to 20,000 (M_n ) depending on the method of determination of gelation temperature. To reduce the gelation temperature of MC close to physiological temperature (37°C), 6% NaCl was added in the different MC‐PEG combinations containing different molecular weight of PEG. It was observed that the drug release time increased from 5 to 8 h with the increase in molecular weight of PEG from 400 to 20,000 (M_n ) and this was due to the maximum viscosity and gel strength of MC‐PEG20000‐NaCl ternary combination. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Physicochemical characterization of poly(ethylene glycol) plasticized poly(methyl vinyl ether‐co‐maleic acid) films

The influence of the poly(ethylene glycol) (PEG) plasticizer content and molecular weight on the physicochemical properties of films cast from aqueous blends of poly(methyl vinyl ether‐co‐maleic acid) (PMVE/MA) was investigated with tensile mechanical testing, thermal analysis, and attenuated total reflectance/Fourier transform infrared spectroscopy. Unplasticized films and those containing high copolymer contents were very difficult to handle and proved difficult to test. PEG with a molecular weight of 200 Da was the most efficient plasticizer. However, films cast from aqueous blends containing 10% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000 when the copolymer/plasticizer ratio was 4 : 3 and those cast from aqueous blends containing 15% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000 when the copolymer/plasticizer ratio was 2 : 1 possessed mechanical properties most closely mimicking those of a formulation we have used clinically in photodynamic therapy. Importantly, we found previously that films cast from aqueous blends containing 10% (w/w) PMVE/MA performed rather poorly in the clinical setting, where uptake of moisture from patients' skin led to reversion of the formulation to a thick gel. Consequently, we are now investigating films cast from aqueous blends containing 15% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000, where the copolymer/plasticizer ratio is 2 : 1, as possible Food and Drug Administration approved replacements for our current formulation, which must currently be used only on a named patient basis as its plasticizer, tripropylene glycol methyl ether, is not currently available in pharmaceutical grade. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Effect of process parameters on the melt granulation of pharmaceutical powders

Co-melt granulation of lactose and PEG was investigated in a fluidised bed granulator. The effect of process parameters such as binder content and binder viscosity were correlated to granulation time and particle size distribution. The experimental data indicated that after initial nucleation the granulation mechanism was dependent upon binder content and binder viscosity. When the binder content was increased above 18% (w/w) de-fluidisation of the bed occurred and granulation moved to the slurry regime. As the process involved the melt granulation of relatively high molecular weight (6-20 k) and thus high viscosity PEG (500-19000 mPa s), it was found that binder viscosity had a significant affect on the granule growth mechanism. Granulation with a binder viscosity of 500 mPa s resulted in granule growth by coalescence, however, an increase in binder viscosity resulted in less coalescence and a lower granule growth rate. Furthermore, the granulation data were characterised by Stokes number analysis.     

Optimization of recovery of esterase from Serratia marcescens using combination of the solvent impregnated resin and aqueous two-phase extraction techniques

ABSTRACT

The performance of tunable aqueous polymer phase impregnated resins (TAPPIR) which is the combination of the solvent impregnated resin principle and an aqueous two-phase system for the separation of esterase from Serratia marcescens was evaluated in this study. Different molecular weight of polyethylene glycol (PEG) (2000, 4000 and 6000) at concentration ranging from 5% to 20% (w/w) and potassium citrate were used to construct the aqueous phase in TAPPIR technology. Optimum composition of PEG and salt for esterase partitioning was determined using response surface methodology. The optimum condition for the purification of esterase was impregnation of 25% (w/w) of PEG 2000 into 4 mm porous glass beads and extraction of esterase using 15% (w/w) potassium citrate at pH 8 containing 12% (w/w) crude loading with the addition of 4% (w/w) NaCl. Esterase from S. marcescens was successfully purified by the TAPPIR technology up to 5.32 of purification factor with a yield of 75.98%.     

Effect of PEG additives on properties and morphologies of membranes prepared from poly(2,6‐dimethyl‐1,4‐phenylene oxide) by benzyl bromination and in situ amination

This study investigated the effect of PEG additive on the structure formation and permeation properties of membranes. The membranes were prepared from a bromomethylated poly(2,6‐dimethyl‐1,4‐phenylene oxide)/chlorobenzene/ethanol system using the phase inversion method with PEG as an additive. As expected, PEG with a fixed molecular weight (e.g., PEG 600) acted as a pore‐forming agent, and membrane porosity increased as the PEG content of the casting solution increased. However, when the PEG content was fixed, the effect of PEG on the membrane properties and morphology was largely dependent on its molecular weight. It was found that when the molecular weight of PEG was less than 800, it acted as a pore former, but when the molecular weight of PEG was more than 1000, the pore size and porosity of the resulting membrane decreased. These results can be explained by the membrane‐forming system's thermodynamic and kinetic properties, which can be assessed by coagulation value and viscosity. Furthermore, the membranes were characterized for pure water flux and rejection of solute and by SEM observation. The filtration results agreed well with the SEM observations. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 2414–2421, 2005     

Recovery of Human Interferon Alpha-2b from Recombinant Escherichia coli by Aqueous Two-Phase System

Recovery of periplasmic human recombinant interferon alpha-2b (IFN-α2b) from Escherichia coli rosetta-gami2 (DE3) using a single-step polyethylene glycol (PEG)-potassium phosphate aqueous two-phase system (ATPS) was investigated in this study. The influences of system parameters including PEG molecular weight, tie-line length, volume ratio, crude stock loading, system pH, and sodium chloride (NaCl) concentration (%, w/w) were studied. The results showed that the optimum condition to obtain the high purification factor of IFN-α2b in a single step was achieved by ATPS composed of 4% (w/w) PEG 8000, 13% (w/w) potassium phosphate, 0.5% (w/w) NaCl, 10% (w/w) crude stock, and a system pH of 6.5. A purification factor of 26.3 and recovery yield of 40.7% were obtained from optimized ATPS.     

Separation of Bromelain by Aqueous Two Phase Flotation

Aqueous two phase flotation (ATPF) system of polyethylene glycol (PEG) and potassium phosphate is studied for the separation and partial purification of bromelain from the pineapple fruit (Annanus comosus L. Merryl). The effect of PEG molecular weight (1500–20000), concentration of phase forming components (PEG 12–18% w/w and potassium phosphate 14–20% w/w), system pH, nitrogen flow rate, and flotation time were studied and optimum conditions for ATPF were obtained. At optimum conditions of the system, i.e., 14% w/w PEG 1500, 18% w/w potassium phosphate, 80 mL/min of nitrogen flow rate and pH 7, maximum yield of 91.47% and purification fold of 4.26 were obtained. ATPF was found to be an effective technique for the purification of bromelain from pineapple fruit with higher extraction yield and purification fold as compared to aqueous two phase extraction (ATPE).     

Molecular weight effect on theta-gel formation in poly(vinyl alcohol)–poly(ethylene glycol) mixtures

Injectable hydrogel formulations that undergo in situ gelation at body temperature are promising for minimally invasive tissue repair. This work focuses on the investigation of injectable poly(vinyl alcohol) (PVA) and poly(ethylene glycol) (PEG) mixtures. The injectable PVA–PEG aqueous solutions form a hydrogel as temperature is reduced to near body temperature, while filling a defect in the injection site. Gamma sterilization of these solutions compromises injectability presumably due to crosslinking of PVA. We hypothesized that by modifying the PEG molecular weight and its concentration, injectability of radiation sterilized PVA–PEG hydrogels can be optimized without compromising the mechanical properties of the resulting gel. The use of a bimodal mixture of higher and lower molecular weight PEG (600 and 200 g/mol) resulted in lower PVA/PEG solution viscosity, better injectability, and higher gel mechanical strength. The PVA/bimodal-PEG had a lower viscosity at 2733 ± 149 cP versus a viscosity of 5560 ± 278 cP for PVA/unimodal-PEG (400 g/mol). The gel formed with the bimodal PEG mixture had higher creep resistance (61% total creep strain under 0.5 MPa) than that formed with unimodal PEG (84%). These hydrogel formulations are promising candidates for minimally invasive tissue repair. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Aqueous two-phase extraction of punicalagin (α+β) from pomegranate peel by response surface methodology

In order to enhance the recovery of punicalagin from pomegranate peel, extraction of punicalagin (α + β) was studied using aqueous two-phase system. Box Behnken design of response surface methodology was used as a tool to study the effect of Poly Ethylene Glycol (PEG) concentration, PEG molecular weight, salt concentration, solute amount and pH on the extraction yield of punicalagin. The optimal conditions were found to be 18% (w/v) PEG concentration, 8000 PEG molecular weight, 16% (w/v) salt concentration, 0.5 g solute amount and 6 pH. Under these conditions, experimental yield and predicted yield was found to be 43% and 48%, respectively.     

Extraction of microbial transglutaminase from <Emphasis Type="Italic">Amycolatopsis</Emphasis> sp. fermentation broth using aqueous two-phase system

Partitioning of microbial transglutaminase (MTG) from Amycolatopsis sp. in the polyethylene glycol (PEG)/salt-based ATPS was investigated for the first time. The key parameters such as the molecular weight of PEG (PEG 600-6000), the type and concentration of phase-forming salt (ammonium sulfate or phosphates), the pH of system (pH 5.0-8.5), and the concentration of neutral salt (0-6% NaCl, w/w) were determined. The partition coefficient of the enzyme was not linear with PEG molecular weight; PEG1000 gave better yield than others. The concentration of PEG1000, ammonium sulfate and NaCl, and the system pH showed effects with different extents on specific activity (SA) and yield of the enzyme. In the ATPS of 26% w/w PEG 1000 and 19% w/w ammonium sulfate in the presence of 5% w/w NaCl and at pH 6.0, MTG was partitioned into the PEG-rich phase with a maximum yield of 86.51% and SA was increased to 0.83. The results of SDS-PAGE showed the MTG produced by the test strain differed from the enzymes reported before. Thus, this study proves that ATPS can be used as a preliminary step for partial purification of MTG from Amycolatopsis sp. fermentation broth.     

Application of Aqueous Two‐Phase Systems for the Potential Extractive Fermentation of Cyanobacterial Products

The potential use of aqueous two‐phase systems (ATPS) to establish a viable protocol for the in situ recovery of cyanobacterial products was evaluated. The evaluation of system parameters such as poly (ethylene glycol) (PEG) molecular mass, concentration of PEG and salt was carried out to determine the conditions under which Synechocystis sp. PCC 6803 cell and cyanobacterial products, i.e., β‐carotene and lutein, become concentrated in opposite phases. PEG‐phosphate ATPS proved to be unsuitable for the recovery of cyanobacterial products due to the negative effect of the salt upon the cell growth. The use of ATPS PEG‐dextran (6.6 % w/w PEG 3350, 8.4 % w/w dextran 66900, TLL 17.3 % w/w, V_R 1.0, pH 7) and (4.22 % w/w PEG 8000, 9.77 % w/w dextran 66900, TLL 18 % w/w, V_R 1.0, pH 7) resulted in the growth of cyanobacteria (Synechocystis sp. PCC 6803) and the concentration of lutein in opposite phases. However, β‐carotene was seen to concentrate in the top phase together with the biomass. The results reported here demonstrate the potential application of ATPS to establish the conditions for an extractive fermentation prototype process for the recovery of cyanobacterial products.     

Synthesis and characterisation of polyurethanes derived from waste black liquor lignin

Waste black liquor lignin, obtained from bagasse from the small-scale paper industry, can be utilized for the synthesis of polyurethanes (PUs). Several polyurethane samples were prepared from laboratory black liquor (LBL) by reacting varying amounts of lignin ranging from 5 to 70% (w/v) in poly(ethylene glycol) (PEG) (having molecular weights of 200, 600, 1000, 1500 and 4000) with tolylene 2,4-diisocyanate (TDI). The effects of lignin concentration and molecular weight of PEG on mechanical and thermal properties of PUs obtained were investigated. The polyurethanes synthesised were characterized for different properties such as shear strength, adhesion and thermal stability. The shear strength of PU joints with aluminum was found to decrease with increase in both lignin concentration and molecular weight of PEG. Maximum shear strength, i.e. 3.6 N/mm², was shown by 50% (w/v) lignin in PEG of molecular weight 200.     

Strongly thixotropic viscosity behavior of dimethylsulfoxide solution of polyrotaxane comprising α-cyclodextrin and low molecular weight poly(ethylene glycol)

A strong thixotropic viscosity behavior was observed when polyrotaxane prepared from α-cyclodextrins (CDs) and poly(ethylene glycol) (PEG) with a molecular weight of 2000 was dissolved in dimethylsulfoxide (DMSO). A 10 wt% solution liquefied by vigorous shaking was rapidly gelated by standing - this sol-gel transition was reversible. The time for recovering the viscosity was dependent on the polyrotaxane concentration, i.e., a 10 wt% solution regelated within 30 s, whereas several hours were required for the gelation of a 2.5 wt% solution. The thixotropic nature of the solution was also confirmed by the clockwise hysteresis curve of the viscosity when the shear rate was increased and decreased. The gel permeation chromatography (GPC) measurement of the polyrotaxane in DMSO exhibited peaks in the high molecular weight region. The peak disappeared after the phenylcarbamoylation of polyrotaxane, suggesting that the peak was due to loose aggregations of polyrotaxane in DMSO. On the other hand, the DMSO solution of polyrotaxane prepared from CD and PEG with a molecular weight of 3350 - whose inclusion ratio (51%) is slightly lower than that of PEG2000 polyrotaxane (72%) - neither demonstrated the abovementioned thixotropic viscosity nor the peak corresponding to the aggregations occurring during the GPC measurement. The thixotropic behavior was speculated to be caused by the combined contribution of intermolecular attractive hydrogen bonding and higher rigidity of polyrotaxane prepared from PEG2000 than that of polyrotaxane prepared from PEG3350, presumably due to the higher inclusion ratio of the former than that of the latter.     

Recovery and partial purification of thermophilic β-xylosidase derived from recombinant Bacillus megaterium MS941 by aqueous two-phase system

A polymer–salt-based aqueous two-phase system (ATPS) was developed for the effective extraction and purification of extracellular β-xylosidase from the fermentation broth of recombinant Bacillus megaterium MS941. The effect of molecular weight (MW) of polyethylene glycol (PEG), tie-line length (TLL), volume ratio (V_R), crude loading and pH on the recovery performance was evaluated. Under the optimal extraction conditions, β-xylosidase was successfully purified up to 23-fold with a recovery yield of 99% in the bottom salt-rich phase at PEG 4,000/potassium phosphate ATPS comprising TLL of 41.8, V_R of 2.3, crude loading (C_L) of 30% (w/w) at pH 6.     

Polyphenolic extracts of Pinus radiata bark and networking mechanisms of additive‐accelerated polycondensates

The use of various chemicals for extracting polyphenolic fractions (tannins) from Pinus radiata bark was examined with the aim of obtaining high yields of high‐quality tannins to be used as wood adhesives. Extractions carried out under very highly alkaline conditions (pH > 10.5) gave relatively high yields but also excessive viscosity values even in 30% (w/w) solutions, and this demonstrated their inability to function as wood adhesives. Solutions (30% w/w) of mildly extracted (pH < 8.3) fractions gave workable viscosity values and were used in a subsequent study. A rapid acceleration effect was observed in these fractions when ammonia was used as a catalyst. Solid‐state, cross‐polarization/magic‐angle‐spinning ¹³C‐NMR of the cured samples showed evidence proving the existence of benzyl amine bridging networks in their hardened state. Simultaneously accelerated copolymerization could be observed in phenol–resorcinol–formaldehyde/P. radiata bark tannin mixtures with the addition of ammonia, as indicated by viscosity measurements. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2487–2493, 2007     

The preparation of ultra narrow molecular weight distribution poly(ethylene glycol)s by fractional crystallization from solution

The preparation of very narrow molecular weight distribution poly(ethylene glycol) (PEG) was investigated by fractional crystallization from solution. Fractionation experiments were conducted from the solutions of 1500, 2000, and 3000 molecular weight PEG in n‐butanol/n‐heptane mixtures. Size Exclusion Chromatography and Differential Scanning Calorimetric studies were performed for the characterization of fractions prepared at different crystallization temperatures and times. By suitable choice of these experimental parameters it was possible to obtain PEG fractions with M_w/M_n ≤ 1.05. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 79: 1999–2005, 2001     

Minimizing the surface effect of PDMS–glass microchip on polymerase chain reaction by dynamic polymer passivation

Polydimethyl siloxane (PDMS)–glass microchip has a very strong surface effect on polymerase chain reaction (PCR), leading to a very poor PCR yield. In the work reported here, practical dynamic passivation of surfaces of PDMS–glass microchip using polyethylene glycol (PEG) or polyvinylpyrrolidone (PVP) was achieved using a conventional thermocycler. The passivation procedure was cost‐effective and easy to conduct. The effects of polymer molecular weight and polymer concentration on tube PCR efficiency were investigated primarily to prescreen out suitable polymers and polymer concentrations in the PCR mixture. The result from tube PCR indicated that both PEG and PVP could affect the performance of Taq polymerase. A final concentration of 0.025% (w/v) or 0.4% (w/v) polymer in the PCR mixture can enhance the tube PCR, while 1% (w/v) polymer was found to inhibit the reaction. PEG was more effective in tube PCR, although PVP performed better in chip PCR. Instead of employing the polymer directly in the PCR mixture, i.e. the conventional in situ passivation approach, another approach of dynamic passivation by pre‐injecting polymers into the microchip achieved better performance. The efficiency of pre‐passivation was found to follow the order: PVP10000>PVP55000, PEG8000> PEG10000>PEG400. After pre‐passivation with PVP10000, PVP55000 and PEG8000, the PCR efficiency can recover to 93%, 86% and 83%, respectively, of that obtained from tube PCR. Copyright © 2006 Society of Chemical Industry     

Preparation and properties of nonionic polyol dispersion from terpinene‐maleic ester‐type epoxy resin

A nonionic epoxy‐based polyol (NTP) which can be used in place of the commonly used polyol dispersions to prepare two‐component waterborne polyurethanes was synthesized with terpinene‐maleic ester‐type epoxy resin (TME), polyethylene glycol (PEG), and trimethylopropane (TMP) in the presence of sulfuric acid as catalyst. The synthesis process was tracked with gel permeation chromatography (GPC) and differential scanning calorimetry (DSC) by investigating the changes of molecular weight and glass transition temperature (T_g) of the product. FTIR was used to characterize the chemical structure of NTP. Major technical parameters of NTP were as follows: hydroxyl value 100 mg/g, hydroxyl group content 3.04%, T_g 4.03°C, and viscosity 150 mPa s (40% solid content). Effect of molecular weights and dosages of PEG on stability of NTP dispersion was examined by particle size analyses. It was found that stable dispersion was obtained when using PEG6000 as hydrophilic chain and its dosage ≥8% by the weight of TME. The average particle size of the prepared dispersion was about 200 nm from particles size and TEM analyses. The NTP dispersion showed characteristic of shear thinning, which indicated it was a pseudoplastic fluid. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Potential application of aqueous two‐phase systems for the fractionation of RNase A and α‐Lactalbumin from their PEGylated conjugates

BACKGROUND: PEGylation reactions often result in a heterogeneous population of conjugated species and unmodified proteins that presents a protein separations challenge. Aqueous two‐phase systems (ATPS) are an attractive alternative for the potential fractionation of native proteins from their PEGylated conjugates. The present study characterizes the partition behaviors of native RNase A and α‐Lac and their mono and di‐PEGylated conjugates on polyethylene glycol (PEG)—potassium phosphate ATPS. RESULTS: A potential strategy to separate unreacted native protein from its PEGylated species was established based upon the partition behavior of the species. The effect of PEG molecular weight (400–8000 g mol^?1), tie‐line length (15–45% w/w) and volume ratio (V_R; 0.33, 1.00 and 3.00) on native and PEGylated proteins partition behavior was studied. The use of ATPS constructed with high PEG molecular weight (8000 g mol^?1), tie‐line lengths of 25 and 35% w/w, and V_R values of 1.0 and 3.0 allowed the selective fractionation of native RNase A and α‐Lactalbumin, respectively, from their PEGylated conjugates on opposite phases. Such conditions resulted in an RNase A bottom phase recovery of 99%, while 98% and 88% of mono and di‐PEGylated conjugates, respectively were recovered at the top phase. For its part, α‐Lac had a bottom phase recovery of 92% while its mono and di‐PEGylated conjugates were recovered at the top phase with yields of 77% and 76%, respectively. CONCLUSIONS: The results reported here demonstrate the potential application of ATPS for the fractionation of PEGylated conjugates from their unreacted precursors. Copyright © 2010 Society of Chemical Industry     

A novel mucoadhesive polymer prepared by template polymerization of acrylic acid in the presence of poly (ethylene glycol)

A new mucoadhesive polymer was prepared by template polymerization of acrylic acid in the presence of poly(ethylene glycol) (PEG). FTIR results indicated that a polymer complex was formed between poly(acrylic acid) (PAA) and PEG through hydrogen bonding. The hydrogen bonding in the PAA/PEG polymer complex was stronger than that in the PAA/PEG blend, and became stronger as the molecular weight of PEG increased. Glass transition temperatures (T_g) of PAA in the PAA/PEG polymer complexes was shifted to a lower temperature than that of PAA in the PAA/PEG blend. However, they tended to become higher as the molecular weight of PEG increased. The dissolution rate of the PAA/PEG polymer complex was much slower than the PAA/PEG blend, and was dependent on pH and molecular weight of the PEG. The mucoadhesive force of the PAA/PEG polymer complexes was stronger than for the PAA/PEG blend or a commercial product, Carbopol 971P NF. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 73: 2749–2754, 1999