Raman spectroscopy as a tool for measuring mutual-diffusion coefficients in hydrogels

Raman spectroscopy has been exploited to characterize the diffusion properties of solutes in hydrogels. Raman active vibrations were used as intrinsic probes of the solute concentration along gel cylinders. The resulting one-dimensional solute distribution, characterized as a function of both time and space, could be analyzed with a model based on Fick's diffusion law, and the mutual-diffusion coefficient (Dm) was then determined. To illustrate the potential of this approach, we measured the Dm of two polyethylene glycols (PEG) in Ca-alginate gels. In this case, the intensity of the CH stretching band was used to obtain the concentration profiles of PEGs, whereas the OH stretching band of water was used as an internal intensity standard. In addition to providing a straightforward approach to measuring diffusion coefficients, the Raman profile analysis provides information relative to the accessibility of gels to large molecules. As an example, it was found that the PEG penetration in Ca-alginate gels was restricted, a phenomenon that was dependent on PEG size. The Raman technique presented here effectively characterizes transport properties of solutes in gels, and such characterization is required for developing several technical applications of gels, such as their use as materials for controlled release of drugs.     

Poly(ethylene glycol) Vesicles: Self-Assembled Site for Luminescence Generation

Fluorescence in poly(ethylene glycol) (PEGs 400-12000) solutions is reported here for the first time. PEG solutions form a vesicular organization with the hydrophilic groups attached at both ends which arrange themselves beyond a particular concentration and offer electron-dense regions at the center of the vesicle. These vesicles provide an inherent site for fluorescence generation in PEG solutions. Fluorescence emission was observed at ～380 nm with an excitation wavelength of 300 nm. PEG of molecular weight 6000 was found to show maximum emission intensity at a particular concentration. The formation of PEG vesicles (～1 nm size) was confirmed by dynamic light scattering (DLS) and confocal laser microscopy. On addition of metal ions the polymeric vesicle breaks up to monomeric PEG, and hence, the fluorescence intensity decreases with a red shift. Fluorescence lifetime measurements indicate the nature of complexation of the metals with PEG. Since PEGs are used as one of the phases in aqueous biphasic systems (ABS) of liquid-liquid extractions, the nature of the fluorescence emission spectrum of the PEG phase after extraction was studied. Metal extraction in the PEG-rich phase of an ABS leads to quenching of fluorescence in PEG.     

An investigation into the low-frequency dielectric response of polyethylene glycols

The dielectric response of a series of polyethylene glycols (PEGs) in the molecular weight range 3400–20 000 has been studied using low-frequency dielectric spectroscopy. In the molten state, a Maxwell-Wagner response was seen, indicating a conducting bulk in series with a barrier layer of high capacitance. The high-frequency conductance was shown to be activated, with a higher activation energy being seen for PEG 3400 than for the other three molecular weight samples, all of which possessed similar values. On solidification, the samples showed spectra which corresponded to a high-frequency response of comparatively small magnitude with a larger response being observed as the frequency was lowered. The low-frequency conductance decreased with chain length, although no other relationship was found between the components of the dielectric response and the molecular weight.     

Effect of polyethylene glycol on the mechanical property, microstructure, thermal stability, and flame resistance of phenol–urea–formaldehyde foams

In this study, polyethylene glycol (PEG) was added to phenol–urea–formaldehyde foam to improve its toughness, and the effects of PEG, with different molecular weights and dosages, on the mechanical property, microstructure, thermal stability, and flame resistance of phenol–urea–formaldehyde foam were studied. The addition of PEG significantly increased the toughness and impact strength and decreased the pulverization rate of the foam. The compression strength of the foam first increased and then decreased with increasing amounts of PEG. When 2 wt% PEGs were added, the compression strength of foams was the highest. The addition of PEG significantly influenced the microstructure of phenol–urea–formaldehyde foams, in which the cell diameter decreased and wall thickness increased with increasing amount and molecular weight of PEG. The addition of PEG also slightly decreased the thermal stability of phenol–urea–formaldehyde foams, and increased the heat release rate, total heat release, and total smoke release of the foams.     

In vitro release studies of flurbiprofen from different topical formulations

The release profiles of flurbiprofen (F) from different gel and ointment formulations were studied in order to evaluate factors governing the release process. Carbopol 934P (CAB), poloxamer 407 (POL), and eudragit S100 (EUD) gel bases were used, while emulsion (EML) and polyethylene glycol (PEG) ointments were employed. The release studies were conducted using membraneless diffusion cells and lipophilic receptor medium, isopropyl myristate (IPM). The effects of gelling agent concentrations and the initial drug load on drug release were determined. Hydrogels were observed to give higher amounts of drug release than hydrophobic EUD gel and ointments, despite the lower bulk viscosity of these bases. Flurbiprofen release from CAB gels was 3.06-1.56-fold higher than from other formulations. Over a 4-hr period, the amount of F released was 492.8 and 316.0 µg/cm² from 2% CAB and 25% POL gels, while it was 213.05, 168.61, and 160.9 µg/cm² from EML, 40% EUD, and PEG bases, respectively. The diffusivity of F in the gel bases was an inverse function of the polymer concentrations over the range of 1-3% CAB, 20-30% POL, and 35-45% EUD gels. Drug release was increased from the bases as the initial F concentration increased over the range 0.25-1.0%, while the diffusion coefficient observed an inverse relationship. The CAB and POL gels could be the vehicles of choice for the rapid release and onset of F after topical application.     

Microencapsulation by Emulsion Non-Solvent Additicin Method

Abstract

Cellulose acetate butyrate microcapsules containing propranolol were prepared by emulsion non-solvent addition method. The effects on drug release of different polyethylene glycols (PEG), various concentrations of PEG 4000, and particle size of the drug to be encapsulated were investigated. In vitro dissolution of microcapsules in simulated intestinal fluid and buffers at different pH was also studied. PEGs were found to increase drug release for this system. The pH dissolution profiles of the microcapsules indicated that dissolution was slightly pH dependent during the first 8 hours of dissolution.     

Effect of molecular weight and ratio of poly ethylene glycols’ derivatives in combination with trehalose on stability of freeze-dried IgG

The influence of poly ethylene glycol (PEG) at different molecular weights (MWs) and ratios was studied on the stability of freeze-dried immune globulin G (IgG). PEGs (600–4000 Dalton) at concentrations of 0.5 and 5% W/V were applied in the presence of 40 and 60% W/W of trehalose to prepare freeze-dried IgG formulations. Size-exclusion chromatography, infra-red spectroscopy, differential scanning calorimeter, and gel electrophoresis were performed to characterize lyophilized samples. Pure IgG demonstrated the highest aggregation of 5.77?±?0.10% after process and 12.66?±?0.50% as well as 44.69?±?0.50% upon 1 and 2?months of storage at 45?°C, respectively. 5% W/V of PEGs 4000 in combination with 40% W/W trehalose, significantly suppressed aggregation, 0.05?±?0.01%, with minimum aggregation rate constant of 0.32 (1/month). The integrity of IgG molecules and secondary conformation were properly preserved in all formulations comparing native IgG. It could be concluded that appropriate concentration and MW of PEGs, prominently augmented stabilizing effect of trehalose on freeze-dried antibody through inserting additional supportive mechanisms of actions.     

In Vitro Release Studies of Flurbiprofen from Different Topical Formulations

ABSTRACT

The release profiles of flurbiprofen (F) from different gel and ointment formulations were studied in order to evaluate factors governing the release process. Carbopol 934P (CAB), poloxamer 407 (POL), and eudragit S100 (EUD) gel bases were used, while emulsion (EML) and polyethylene glycol (PEG) ointments were employed. The release studies were conducted using membraneless diffusion cells and lipophilic receptor medium, isopropyl myristate (IPM). The effects of gelling agent concentrations and the initial drug load on drug release were determined. Hydrogels were observed to give higher amounts of drug release than hydrophobic EUD gel and ointments, despite the lower bulk viscosity of these bases. Flurbiprofen release from CAB gels was 3.06–1.56-fold higher than from other formulations. Over a 4-hr period, the amount of F released was 492.8 and 316.0 µg/cm² from 2% CAB and 25% POL gels, while it was 213.05, 168.61, and 160.9 µg/cm² from EML, 40% EUD, and PEG bases, respectively. The diffusivity of F in the gel bases was an inverse function of the polymer concentrations over the range of 1–3% CAB, 20–30% POL, and 35–45% EUD gels. Drug release was increased from the bases as the initial F concentration increased over the range 0.25–1.0%, while the diffusion coefficient observed an inverse relationship. The CAB and POL gels could be the vehicles of choice for the rapid release and onset of F after topical application.     

New synthesis processes of polyetheramines: Comparison of three different developed amination routes

In this work, three different novel processes are reported for the preparation of polyetheramines (PEAs) from polyethylene glycols (PEGs) and polypropylene glycols (PPGs). The processes are the nucleophilic substitution, oxidation/reduction, and catalytic aminations. The novelties of the processes lay in environmentally friendly routes, the variety of possible precursors (i.e., PEG and PPG with different molecular weights), and extraction methods. The formation of the PEAs with no chain cleavage was confirmed by nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC) results. Based on the comparison study, the nucleophilic substitution and catalytic aminations were the most efficient (conversion >90%) and shortest (yield >90%) methods, respectively. For nucleophilic substitution, the amination of PEG and PPG intermediates was performed in different solvent media due to the difference in solubility parameters of PEGs and PPGs. The catalytic route (using [Zn(tu)₃]SO₄/aqueous ammonia system) can be considered a green method; however, catalytic amination of the PPGs is impossible due to insolubility of PPGs in aqueous ammonia. Therefore, the oxidation/reduction method using Leuckart reaction appears to be the most environmentally friendly route for the amination of PPGs. Moreover, PEGs and PPGs with different molecular weights showed various behaviors during reaction and separation protocols.     

Retardation of Polymeric Carrier Dissolution by Dispersed Drugs: Factors Influencing the Dissolution of Solid Dispersions Containing Polyethlene Glycols

Molecular weight is an important determinant of plyethylene glycol (PEG) dissolution rate: the rate decreasing as the molecular weight is increased. PEG samples of equivalent nominal. molecular weight had different dissolution properties. Intrinsic viscosity and differential scanning calorimetry suggested that the observed differences my be related to molecular weight variation between samples. The dissolution rate of PEG from solid dispersions is retarded, the effect being dependent on the chemical nature of the drug and its concentration. Phenobarbitone was particularly potent in retarding PEG dissolution. Phenobarbitone dissolution rate was retarded from dispersions of high phenobarbitone content. However drug dissolution from solid dispersions low in phenobarbitone were greater than that of pure phenobarbitone. The low dissolution rates were explained in terms of formation of the 2:1 PEG monomer: phenobarbitone complex during solid dispersion formation. At high PEG weight fractions (i.e. 30:1, 50:1) drug dissolution was carrier controlled and although PEG dissolution was greatly suppressed, it was sufficiently large to transport the drug into solution at a rate greater than that of pure phenobarbitone.     

Retardation of Polymeric Carrier Dissolution by Dispersed Drugs: Factors Influencing the Dissolution of Solid Dispersions Containing Polyethlene Glycols

Molecular weight is an important determinant of plyethylene glycol (PEG) dissolution rate: the rate decreasing as the molecular weight is increased. PEG samples of equivalent nominal. molecular weight had different dissolution properties. Intrinsic viscosity and differential scanning calorimetry suggested that the observed differences my be related to molecular weight variation between samples. The dissolution rate of PEG from solid dispersions is retarded, the effect being dependent on the chemical nature of the drug and its concentration. Phenobarbitone was particularly potent in retarding PEG dissolution. Phenobarbitone dissolution rate was retarded from dispersions of high phenobarbitone content. However drug dissolution from solid dispersions low in phenobarbitone were greater than that of pure phenobarbitone. The low dissolution rates were explained in terms of formation of the 2:1 PEG monomer: phenobarbitone complex during solid dispersion formation. At high PEG weight fractions (i.e. 30:1, 50:1) drug dissolution was carrier controlled and although PEG dissolution was greatly suppressed, it was sufficiently large to transport the drug into solution at a rate greater than that of pure phenobarbitone.     

Gas-phase proton-transfer chemistry coupled with TOF mass spectrometry and ion mobility-MS for the facile analysis of poly(ethylene glycols) and PEGylated polypeptide conjugates

Gas-phase ion/molecule chemistry has been combined with ion mobility separation and time-of-flight mass spectrometry to enable the characterization of large poly(ethylene glycol)s (PEGs) and PEGylated molecules (>40 kDa). A facile method is presented in which gas-phase superbases are reacted in the high-pressure source region of commercial TOF mass spectrometers to manipulate the charge states of large ions generated by electrospray ionization (ESI). Charge stripping decreases the spectral congestion typically observed in ESI mass spectra of high molecular weight polydisperse PEGylated molecules. From these data, accurate average molecular weights and molecular weight distributions for synthetic polymers and PEGylated proteins are determined. The average MW measured for PEGylated Granulocyte colony-stimulating factor (rh-GCSF, 40 726.2 Da) is in good agreement with the theoretical value, and a 16 Da mass shift is easily observed in the spectrum of an oxidized form of the heterogeneous PEGylated protein. Ion mobility separations can fractionate PEGs of different chain length; when coupled with charge stripping ion/molecule reactions, ion mobility mass spectrometry (IMMS) offers several analytical advantages over mass spectrometry alone for the characterization of large PEGylated molecules including enhanced dynamic range, increased sensitivity, and specificity. Low abundance free PEG in a PEGylated peptide preparation, which is not directly detectable by mass spectrometry, can be easily observed and accurately quantified with gas-phase ion/molecule chemistry combined with ion mobility mass spectrometry.     

Rheological characterization of hydroxypropylcellulose gels

The present paper describes the rheological properties of hydroxypropylcellulose (HPC) gels formulated in propylene glycol (PG), water, ethanol, and mixtures of these components. The effects of molecular weight, polymer concentration, and solvent composition on the apparent viscosity and flow characteristics have been studied by continuous shear rheometry. The HPC gels are shear thinning and do not exhibit significant yield or hysteresis in their rheograms. The apparent viscosity increases with increasing molecular weight and concentration of the polymer, as expected. Although not so pronounced at lower concentrations (≤ 1.5%), HPC gels tend to become increasingly non-Newtonian with increasing molecular weight at higher polymer concentrations (3%). A mathematical model has been proposed for the prediction of viscosities of HPC gels. There exists a high degree of dependence on molecular interactions between various solvent molecules in the prediction of mixture viscosities in ternary systems. The effects of solvent composition on the viscoelastic behavior of these gels have also been examined by dynamic mechanical analysis. The HPC gels are highly viscoelastic and exhibit greater degrees of elasticity with increased PG content in ternary solvent mixtures with water and ethanol. The study also suggests that dynamic mechanical analysis could prove to be a useful tool in the determination of zero-shear viscosities, viscosities that are representative of most realistic situations.     

Microencapsulation by Emulsion Non-Solvent Additicin Method

Cellulose acetate butyrate microcapsules containing propranolol were prepared by emulsion non-solvent addition method. The effects on drug release of different polyethylene glycols (PEG), various concentrations of PEG 4000, and particle size of the drug to be encapsulated were investigated. In vitro dissolution of microcapsules in simulated intestinal fluid and buffers at different pH was also studied. PEGs were found to increase drug release for this system. The pH dissolution profiles of the microcapsules indicated that dissolution was slightly pH dependent during the first 8 hours of dissolution.     

Rheological Characterization of Hydroxypropylcellulose Gels

The present paper describes the rheological properties of hydroxypropylcellulose (HPC) gels formulated in propylene glycol (PG), water, ethanol, and mixtures of these components. The effects of molecular weight, polymer concentration, and solvent composition on the apparent viscosity and flow characteristics have been studied by continuous shear rheometry. The HPC gels are shear thinning and do not exhibit significant yield or hysteresis in their rheograms. The apparent viscosity increases with increasing molecular weight and concentration of the polymer, as expected. Although not so pronounced at lower concentrations (≤ 1.5%), HPC gels tend to become increasingly non-Newtonian with increasing molecular weight at higher polymer concentrations (3%). A mathematical model has been proposed for the prediction of viscosities of HPC gels. There exists a high degree of dependence on molecular interactions between various solvent molecules in the prediction of mixture viscosities in ternary systems. The effects of solvent composition on the viscoelastic behavior of these gels have also been examined by dynamic mechanical analysis. The HPC gels are highly viscoelastic and exhibit greater degrees of elasticity with increased PG content in ternary solvent mixtures with water and ethanol. The study also suggests that dynamic mechanical analysis could prove to be a useful tool in the determination of zero-shear viscosities, viscosities that are representative of most realistic situations.     

3D polylactide-based scaffolds for studying human hepatocarcinoma processes in vitro

We evaluated the combination of leaching techniques and melt blending of polymers and particles for the preparation of highly interconnected three-dimensional polymeric porous scaffolds for in vitro studies of human hepatocarcinoma processes. More specifically, sodium chloride and poly(ethylene glycol) (PEG) were used as water-soluble porogens to form porous and solvent-free poly(L,D-lactide) (PLA)-based scaffolds. Several characterization techniques, including porosimetry, image analysis and thermogravimetry, were combined to improve the reliability of measurements and mapping of the size, distribution and microarchitecture of pores. We also investigated the effect of processing, in PLA-based blends, on the simultaneous bulk/surface modifications and pore architectures in the scaffolds, and assessed the effects on human hepatocarcinoma viability and cell adhesion. The influence of PEG molecular weight on the scaffold morphology and cell viability and adhesion were also investigated. Morphological studies indicated that it was possible to obtain scaffolds with well-interconnected pores of assorted sizes. The analysis confirmed that SK-Hep1 cells adhered well to the polymeric support and emitted surface protrusions necessary to grow and differentiate three-dimensional systems. PEGs with higher molecular weight showed the best results in terms of cell adhesion and viability.     

Dependence of drying technique on surface area and pore size for polyethylene glycol/tetramethoxysilicate hybrid gels

The effect of drying technique on the surface area and pore size of ethylene glycol/polyethylene glycol (PEG)/tetramethoxysilicate hybrid gels is presented. Various molecular weight polyethylene glycols were added to acid-catalyzed solutions of tetramethoxysilane (TMOS) in methanol. The two drying techniques investigated were supercritical CO₂ drying and conventional evaporation. Nitrogen adsorption was used to determine the surface area and pore radius. As the molecular weight of the polyethylene glycol increased, the pore size of the gel increased, and the surface area decreased. For gels with no polymer additive, both the surface area and pore size of the gels is dependent on the drying method. However, when the various polymers were added, this difference became insignificant, indicating that the polymer assists in opening the pore structure and prevention of syneresis.     

Force spectroscopy on single polymer incorporated into polymer gels

We conducted the extraction experiments of single polymer incorporated into hydrogels with an atomic force microscope (AFM) as a model for investigating nonspecific intermolecular interactions between macromolecules in a semidilute region at the single molecule level. Small amount of poly(ethylene glycol) (PEG) terminated with a thiol group was inserted in poly(acrylamide) gels, and a part of PEG polymer segments on the gel surface was attempted to pull out of the gels with a gold-coated AFM tip. The observed force-distance curves were classified into two kinds of extraction force profiles: a plateau force, which is almost constant irrespective of the tip-surface distance and a nonlinear force, which nonlinearly increases with the extraction length. Characteristic interaction length, L, and force, F, of these extraction force profiles were measured with changing the crosslinker concentration of gels which strongly affects the network structures. As a result, L of these extraction profiles significantly decreased at crosslinker concentrations higher than a standard one at which most gels have been prepared for investigating their physical properties. On the other hand, F showed no obvious difference on the change in crosslinker concentrations both on the plateau and the nonlinear force profiles. The origin of the observed forces was discussed in terms of gel network structures.     

不同相对分子质量聚乙二醇的热氧降解行为

3种不同相对分子质量的聚乙二醇(PEG)在80℃经过不同的老化时间,均发生了不同程度的热氧降解。采用红外光谱法、凝胶渗透色谱法和核磁共振波谱法研究了不同相对分子质量聚乙二醇热氧降解的行为及降解产物结构,定量表征了不同相对分子质量聚乙二醇的降解程度。结果表明,老化时间越长,3种PEG降解生成的小分子酯类化合物越多。其中PEG10000最稳定,不易发生热氧降解,PEG800降解程度最大。     

Diffusion coefficient of the protein in various crystallization solutions: The key to growing high-quality crystals in space

The diffusion coefficients of lysozyme and alpha-amylase were measured in the various polyethylene glycol (PEG) solutions. Obtained diffusion coefficients were studied with the viscosity coefficient of the solution. It was found that the diffusion process of the protein was suppressed with a factor of v^γ, where ν is a relative viscosity coefficient of the PEG solution. The value of γ is ?0.64 at PEG1500 for both proteins. The value increased to ?0.48 at PEG8000 for lysozyme, while decreased to ?0.72 for alpha-amylase. The equation of an approximate diffusion coefficient at certain PEG molecular weight and concentration was roughly obtained.