Aqueous Solutions Of Hydroxypropylmethylcellulose Research Articles

HPMC Hydrogel Formation Mechanisms Unveiled by the Evaluation of the Activation Energy.

Aqueous solutions of hydroxypropyl methylcellulose (HPMC) show inverse thermoreversible gelation, i.e., they respond to small temperature variations exhibiting sol–gel transition during heating, and reversibly gel–sol transition during cooling. According to the pertinent literature on HPMC aqueous systems, at room temperature, the loss modulus (G”) is higher than the storage modulus (G’). During the heating ramp, the viscoelastic response follows a peculiar path: initially, G” and G’ smoothly decrease, then drop to a minimum and finally increase. Eventually, G’ overcomes G”, indicating the gel formation. A recent explanation of this behaviour considers a two-step mechanism: first, phase separation occurs, then fibrils form from a polymer-rich phase and entangle, leading to a three-dimensional network. Based on this, our research focuses on the rheological analysis of the different steps of the sol–gel transition of an HPMC aqueous solution. We perform different viscoelastic tests: thermal ramps, time sweeps, and frequency sweeps at selected characteristic temperatures. We couple classical analysis of the SAOS experiments with an innovative approach based on the evaluation of the activation energy (Ea), made possible by the instrument intrinsic temperature oscillations around the target value. Results show that Ea can be a valid tool that contributes to further clarifying the peculiar microstructural evolution occurring in this kind of thermoreversible gel.

Structural Transition in Dilute Solutions of Rod-Like Macromolecules

On the basis of experimental data obtained for the viscosity in aqueous solutions of hydroxypropyl methylcellulose (metolose), it has been found that a structural transition takes place in dilute solutions of rod-like macromolecules with the increasing temperature. Namely, macromolecules form clusters in which they are arranged in parallel to one another. It is shown that this transition is a set of local phase transitions of the first kind.

Nonequilibrium Fluctuations of Light Scattering Intensity in the Neighborhood of the Phase Transition Temperature

Light scattering in a 3% aqueous solution of hydroxypropyl methylcellulose (metolose) is studied under nonequilibrium conditions within a temperature range of 303–353 K, i.e., in the neighborhood of the phase transition temperature (336 K). It is established that the light scattering intensity undergoes considerable fluctuations in this temperature interval. It is shown that they are caused by quasi-periodic motions (density fluctuations) appearing in the strongly nonequilibrium state of the solution.

A predictive transport model for convective drying of polymer strip films loaded with a BCS Class II drug

Drying is an important unit operation in the manufacturing of polymer strip films as it affects various film quality attributes. Optimal design and control of convective drying process require models that capture the impact of critical process parameters such as air temperature and velocity on the temporal evolution of film thickness and moisture. Here, a detailed transport model was presented to capture moisture diffusion, heat transfer and moving boundary in convective drying of polymer strip films loaded with griseofulvin (GF), a poorly water-soluble drug. It incorporates a solvent diffusivity model based on free-volume theory. Experimentally, film precursor suspensions were prepared by mixing silica-coated and micronized GF powder with an aqueous solution of hydroxypropyl methylcellulose (HPMC)–glycerin. Films were cast and moisture–time variation during drying was measured. The transport model, whose diffusivity parameters were estimated using drying data at a reference condition, was validated at different drying conditions and wet film thicknesses. It delineates underlying mechanisms of drying kinetics and demarcates a smooth transition from constant-rate to falling-rate period. Overall, our results suggest that the transport model is capable of predicting the temporal evolution of moisture and final film thickness at different drying air velocities and temperatures with reasonable accuracy.

Gelation, Phase Separation, and Fibril Formation in Aqueous Hydroxypropylmethylcellulose Solutions.

The thermoresponsive behavior of a hydroxypropylmethylcellulose (HPMC) sample in aqueous solutions has been studied by a powerful combination of characterization tools, including rheology, turbidimetry, cryogenic transmission electron microscopy (cryoTEM), light scattering, small-angle neutron scattering (SANS), and small-angle X-ray scattering (SAXS). Consistent with prior literature, solutions with concentrations ranging from 0.3 to 3 wt % exhibit a sharp drop in the dynamic viscoelastic moduli G' and G″ upon heating near 57 °C. The drop in moduli is accompanied by an abrupt increase in turbidity. All the evidence is consistent with this corresponding to liquid-liquid phase separation, leading to polymer-rich droplets in a polymer-depleted matrix. Upon further heating, the moduli increase, and G' exceeds G″, corresponding to gelation. CryoTEM in dilute solutions reveals that HPMC forms fibrils at the same temperature range where the moduli increase. SANS and SAXS confirm the appearance of fibrils over a range of concentration, and that their average diameter is ca. 18 nm; thus gelation is attributable to formation of a sample-spanning network of fibrils. These results are compared in detail with the closely related and well-studied methylcellulose (MC). The HPMC fibrils are generally shorter, more flexible, and contain more water than with MC, and the resulting gel at high temperatures has a much lower modulus. In addition to the differences in fibril structure, the key distinction between HPMC and MC is that the former undergoes liquid-liquid phase separation prior to forming fibrils and associated gelation, whereas the latter forms fibrils first. These results and their interpretation are compared with the prior literature, in light of the relatively recent discovery of the propensity of MC and HPMC to self-assemble into fibrils on heating.

Microfluidic Fabrication of Hydrocortisone Nanocrystals Coated with Polymeric Stabilisers.

Hydrocortisone (HC) nanocrystals intended for parenteral administration of HC were produced by anti-solvent crystallisation within coaxial assemblies of pulled borosilicate glass capillaries using either co-current flow of aqueous and organic phases or counter-current flow focusing. The organic phase was composed of 7 mg/mL of HC in a 60:40 (v/v) mixture of ethanol and water and the anti-solvent was milli-Q water. The microfluidic mixers were fabricated with an orifice diameter of the inner capillary ranging from 50 µm to 400 µm and operated at the aqueous to organic phase flow rate ratio ranging from 5 to 25. The size of the nanocrystals decreased with increasing aqueous to organic flow rate ratio. The counter-current flow microfluidic mixers provided smaller nanocrystals than the co-current flow devices under the same conditions and for the same geometry, due to smaller diameter of the organic phase stream in the mixing zone. The Z-average particle size of the drug nanocrystals increased from 210–280 nm to 320–400 nm after coating the nanocrystals with 0.2 wt % aqueous solution of hydroxypropyl methylcellulose (HPMC) in a stirred vial. The differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) analyses carried out on the dried nanocrystals stabilized with HPMC, polyvinyl pyrrolidone (PVP), and sodium lauryl sulfate (SLS) were investigated and reported. The degree of crystallinity for the processed sample was lowest for the sample stabilised with HPMC and the highest for the raw HC powder.

THE STUDY OF NATURAL POLYSACCHARIDES: ORGANOLEPTIC, PHYSICAL, CHEMICAL, MICROBIOLOGICAL PROPERTIES, AND THERMODYNAMIC CHARACTERISTICS OF AQUEOUS SOLUTIONS

Natural polysaccharides is a promising raw material for biodegradable polymers production. To properly select sources of their origin would require conformity with safety standards in force for the similar products. This work conducts a study with a view to examine the extent to which the organoleptic, physical and chemical properties of the polysaccharides in question, as well as their safety indicators conform with the provisions of GOST 16280-2002, CAS 11114-20-8 and CAS 9004-65-3. It is determined that the samples selected, namely, agar-agar produced by Panreac (Germany) and Helicon (USA), carrageenan produced by Boc Sciences (USA) and Newgreen Pharmchem Co. (China) and hydroxypropylmethyl cellulose produced by Acros (Belgium) and Ashland Aqualon Functional Ingredients (USA), meet safety requirements for this type of raw material. Simultaneously, we employ high-sensitivity differential scanning calorimetry method to analyze thermodynamic characteristics of natural polysaccharides’ aqueous solutions. It is shown that gels based on agar-agar have high melting temperature and can withstand temperature rise; after, their microscopic structure is not affected by thermal history, and the gel system remains stable. Thermodynamically, aqueous solution of kappa-carrageenan forms more stable gel than iota-carrageenan; strength and melting point of kappa-carrageenan gels can be adjusted by changing the concentration of potassium chloride in the solution. Aqueous solutions of hydroxypropylmethylcellulose are thermodynamically stable. The experimental data obtained confirm the feasibility of natural polysaccharides application in the production of biodegradable polymers.

Chitosan and Cystatin/Lysozyme Preparation as Protective Edible Films Components

This work characterizes biological, physical, and chemical properties of films formed from an aqueous solution of hydroxypropyl methylcellulose (HPMC), with different concentrations of chitosan (CH) and bioactive cystatin/lysozyme preparation (C/L). The properties of biocomposites were examined by Dynamic Mechanical Analysis (DMA), Fourier’s transfer infrared spectroscopy (FTIR), water vapour permeability (WVP), and tensile testing. Antimicrobial activity againstMicrococcus flavus,Bacillus cereus,Escherichia coli,Pseudomonas fluorescens, andCandida famatawas conducted. Films glass transition and storage modulus were dependent on the C/L and CH concentration. Modulus values decreased during the temperature scan and with higher reagents levels. An increase of CH and C/L concentrations in the films resulted in a decrease in tensile strength from 2.62 to 1.08 MPa. It suggests the hydrolyzing influence of C/L, also observed in smaller peak size ofαrelaxation. C/L addition caused shiftingTgto higher temperature. DMA and FTIR analysis proved that HPMC and CH are compatible polymers. Water resistance was improved with rising CH concentration from1.08E-09to7.71E−10 g/m∗s∗Pa. The highest inhibition zone inM. flavusandC. famatawas recorded at the highest concentration of CH and C/L.

Assessment of ocular surface toxicity after topical instillation of nitric oxide donors

To evaluate the ocular surface toxicity of two nitric oxide donors in ex vivo and in vivo animal models: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) in a hydroxypropyl methylcellulose (HPMC) matrix at final concentrations 1.0 and 10.0 mM. Ex vivo GSNO and SNAC toxicities were clinically and histologically analyzed using freshly excised pig eyeballs. In vivo experiments were performed with 20 albino rabbits which were randomized into 4 groups (5 animals each): Groups 1 and 2 received instillations of 150 µL of aqueous HPMC solution containing GSNO 1.0 and 10.0 mM, respectively, in one of the eyes; Groups 3 and 4 received instillations of 150 µL of aqueous HPMC solution-containing SNAC 1.0 and 10.0 mM, respectively, in one of the eyes. The contralateral eyes in each group received aqueous HPMC as a control. All animals underwent clinical evaluation on a slit lamp and the eyes were scored according to a modified Draize eye test and were histologically analyzed. Pig eyeballs showed no signs of perforation, erosion, corneal opacity or other gross damage. These findings were confirmed by histological analysis. There was no difference between control and treated rabbit eyes according to the Draize eye test score in all groups (p>0.05). All formulations showed a mean score under 1 and were classified as "non-irritating". There was no evidence of tissue toxicity in the histological analysis in all animals. Aqueous HPMC solutions containing GSNO and SNAC at concentrations up to 10.0 mM do not induce ocular irritation.

Activity of glucose oxidase immobilized onto Fe3+ attached hydroxypropyl methylcellulose films

Hydroxypropyl methylcellulose (HMPC) insoluble films were prepared by 60Co-γ irradiation of 10% (w/w) aqueous solutions of hydroxypropyl methylcellulose. The adsorption of Fe3+ onto HPMC films was studied in the range of pH 3.0–7.0. The effect of initial concentrations of Fe3+ solutions on adsorption capacity was studied in the range of 100–1000ppm. Maximum adsorption capacity was found as 250mg Fe3+/g dry HPMC film at pH 5.0. The structure and the morphology of Fe3+-attached HPMC film were evaluated by using FTIR/ATR and SEM–EDX methods. Glucose oxidase (GOX) immobilization on both pristine HPMC and maximum Fe3+-attached HPMC film was investigated in aqueous solutions containing different amount of GOX and at different pHs. Maximum GOX adsorption capacity was found as 500mg/g Fe3+-attached HPMC film. Residual activity of GOX on pristine HPMC and Fe3+-attached HPMC films was investigated with changing pH. While maximum residual GOX activity was observed at pH 6.0 for free enzyme, it was obtained by HPMC and Fe3+-attached HPMC at pH 7.0. GOX desorption studies were achieved by using pH 6.0 buffer (I=0.02M) and 0.1M EDTA solutions. The long-term stability and activity studies of GOX, which is immobilized onto Fe3+-attached HPMC films are still under our investigation.

Thin-coating as an alternative approach to improve flow properties of ibuprofen powder

In the present study, thin-coating as a potential method for improving flow properties of cohesive ibuprofen powder was introduced. Briefly, the technique was based on the successive deposition of ultrasound-assisted fine polymer mist onto the surface of the powdered active pharmaceutical ingredient (API), producing individual particles with a hydrophilic thin-coat. A 0.15% m/V aqueous solution of hydroxypropyl methylcellulose (HPMC) was used. Particle size and surface analysis revealed a decrease in the cohesiveness of ibuprofen powder and an increase in the homogeneity of particle surfaces as a result of polymer treatment. Superficial changes caused a substantial improvement on the flowing characteristics of coated substance over uncoated. The enhancement in flow rate proceeded as the uniformity of the HPMC layer increased. In conclusion, the proposed technique is a simple and effective method that can be used as a continuous process to modify API particle surface properties, which in turn improve the handling of poorly flowable powder.

Influence of liquid layers on energy absorption during particle impact

The influence of the thickness of a covering liquid layer and its viscosity as well as the impact velocity on energy loss during the normal impact on a flat steel wall of spherical granules with a liquid layer was studied. Free-fall experiments were performed to obtain the restitution coefficient of elastic–plastic γ-Al 2O 3 granules by impact on the liquid layer, using aqueous solutions of hydroxypropyl methylcellulose with different concentrations for variation of viscosity (1–300 mPa s). In the presence of a liquid layer, increase of liquid viscosity decreases the restitution coefficient and the minimum thickness of the liquid layer at which the granule sticks to the wall. The measured restitution coefficients were compared with experiments performed without liquid layer. In contrast to the dry restitution coefficient, due to viscous losses at lower impact velocity, higher energy dissipation was obtained. A rational explanation for the effects obtained was given by results of numerically solved force and energy balances for a granule impact on a liquid layer on the wall. The model takes into account forces acting on the granule including viscous, surface tension, capillary, contact, drag, buoyancy and gravitational forces. Good agreement between simulations and experiments has been achieved.

Structure and properties of ibuprofen–hydroxypropyl methylcellulose nanocomposite gel

From a mixture of a methanol solution of ibuprofen (IB) and an aqueous solution of hydroxypropyl methylcellulose (HPMC), clear, uniform sol was obtained at the methanol/water proportion 7/3. When sol was brought to dryness, nanocomposite gel was obtained with amorphous IB particles of 20–50 nm dispersed in HPMC matrix. Simultaneous and quick nano-hybridization and amorphization are based on: (i) re-precipitation of IB in the restricted space of HPMC network, and (ii) recombination of hydrogen bonds from those within IB crystal to those between IB and HPMC. Associated change in the properties including dissolution into aqueous medium was discussed briefly in view of application feasibility to pharmaceutical processing.

Thermoreversible gelation of hydroxypropylmethylcellulose in simulated body fluids

The thermoreversible gelation of hydroxypropylmethylcellulose (HPMC) in simulated intestinal/gastric fluids (SIF/SGF) was monitored by microcalorimetry (micro-DSC), turbidity and rheometry. Both SGF and SIF facilitated sol–gel transition in HPMC without changing the patterns of gelation behavior. The sol–gel transition was found to be an entropy driven and temperature dependent process. Solution isotopic effects using Deuteraed water (D 2O) yielded a linear decrease in the temperature of endothermic maximum ( T max) with the increase in the molar ratio of D 2O, indicating that polymer–polymer direct hydrogen bonding (interchain hydrogen bonding) was involved in the gelation process in addition to hydrophobic association. It was found that the T max shifted roughly linear to lower temperature with the increase of SGF/SIF content. This effect can be interpreted by the salting-out effect. Three distinct regions of the enthalpy and entropy changes (Δ H and Δ S) depending on buffer content were observed. However, Δ H and Δ S were linear with HPMC weight concentration. The aqueous solutions of HPMC showed a low critical solution temperature (LCST) and form an elastic gel with increasing temperature. Rheological measurements indicated that the sol–gel transition proceeded in two stages. The gel elasticity was affected by the polymer concentration and buffer content. The results obtained from different techniques are consistent and show similar trends.

Conformation and kinetic characteristics of interactions between local anesthetics and aqueous solutions of hydroxypropylmethylcellulose

Conformation and kinetic characteristics of the interactions of local anesthetics lidocaine (xycaine), tetracaine (dicaine), bupivacaine, and new RU-1117 compound with proven anesthetic activity with Visiton (1% hydroxypropylmethylcellulose in phosphate buffer) were studied. It was found that complex formation between the local anesthetics and hydroxypropylmethylcellulose is a time-dependent reversible process. The equilibrium is attained within 2.5-8.0 h and depends on the chemical nature of local anesthetic.

Universal Suspension Hydrodynamics: Molecular Characterization of Hydroxypropyl Methylcellulose

A study of the rheology of aqueous solutions of hydroxypropyl methylcellulose (HPMC) is presented with the aim of supporting the previously suggested physics, referred to as laminar dynamics, of the viscosity increasing effect per unit volume of particles with extended shape on a flowing suspension. Since it is essential that appropriate flow is employed in order to utilize the proposed model enabling absolute values of the particle's weight average axial ratio a w to be derived from the intrinsic viscosity [η], the shear requirement is studied extensively. Hence, flow curves (viscosity η versus shear rate) for a series of commercial HPMC viscosity grades (3 to 10,000 cP) of USP substitution type 2910 were measured under an extended range of concentrations c (g/dL) and shear rates D (1/s). The results indicate that [η] (dL/g) can be obtained by combining c and D in such a way that either c → 0 (at constant D > 0) or D > D* (at constant c > 0), where D* is a critical shear rate. It may hence be concluded that laminar dynamics is applicable at any constant D > 0 if c → 0, and it is proposed that such flow corresponds to a complete absence of particle–particle interactions leading to a flow in the vicinity of the particle parallel to its length axis. It is demonstrated that the particle–particle interaction tends to become negligible, i.e., the Huggins constant kH → 0 (for extended shape), at any concentration when D > D*. Assuming that the particle–particle interaction is entirely hydrodynamic, i.e., a negligible non-hydrodynamic interaction such as an electrostatic or chemical interaction, at any D, it is possible to derive a universal suspension hydrodynamics, solely determined by the particle shape and concentration under Newtonian conditions and general to any polymer suspension or solution, by combining stationary dynamics (shown empirically to be a universal relation; ηsp = f(c[η]), D → 0) with laminar dynamics (ηsp = c[η], D > D* or c → 0). It is demonstrated how these universal functions can be used for absolute determination of a w and subsequent calculation of such values as molecular weight, size, Mark-Houwink constant, critical (“overlap”) concentration c*, and radius of gyration Rg,w. In addition, a universal suspension characteristic termed critical specific viscosity ηsp* is identified.

Monitoring the Thermal Gelation of Cellulose Ethers in situ Using Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy

In this work attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy was used to probe the thermal gelation behavior of aqueous solutions of hydroxypropyl methylcellulose (HPMC), specifically thermal gelation and accompanying precipitation. Cloud point measurements are usually evaluated through turbidity in dilute solutions but the method cannot readily be applied to more concentrated or highly viscous solutions. From the ATR-FTIR data, intensity changes of the nu(CO) band marked the onset of gelation and information about the temperature of gelation and the effect of the gel structure on the water hydrogen bonding network was elucidated. Changes in the relative intensities of bands associated with the methoxyl groups and hydrogen-bond-forming secondary alcohol groups indicated that hydrophobic polymer chain interactions were involved in the gelation process. The dominance of inter-molecular H bonding over intra-molecular H bonding within the cellulose ether in solution was also observed. The ATR-FTIR data was in good agreement with measurements of turbidity conducted on the same systems. The work indicates significant potential for the use of ATR-FTIR for the investigation of gelation and cloud point measurements in viscous cellulosic formulations.

Preparation of Anode/Electrolyte Ceramic Composites by Coextrusion of Pastes

Anode/electrolyte two-layer ceramic composites for tubular solid oxide fuel cells were prepared through coextrusion of multiple pastes containing a water-based binder (an aqueous solution of hydroxypropyl methylcellulose). The multibillet extrusion (MBE) technique was found to be effective in achieving the anode/electrolyte composite pipes. Furthermore, it is possible to reduce the wall thickness of both anode and electrolyte layers by raising the extrusion ratio of each layer. The extrusion pressure and binder content required to obtain sound extrudates decreased with an increase in the fraction of nickel oxide in an anode layer. It is feasible to decrease the difference in the sintering shrinkage between the anode and electrolyte layers by incorporating calcined coarse yttria-stabilized zirconia (YSZ) powder in the electrolyte layer. The incorporation of coarse YSZ powder in an anode is effective in forming a continuous NiO network within the YSZ matrix.

Thermally induced coupling of phase separation and gelation in an aqueous solution of hydroxypropylmethylcellulose (HPMC)

Thermally induced coupling of gelation and phase separation in polysaccharide aqueous solutions has a complex feature because of critical and tricritical phenomena, thermally induced hydrophobic interaction, and molecular-weight distribution of the polysaccharide. To elucidate the process, the criticality of a hydroxypropylmethylcellulose (HPMC) aqueous solution was assessed, and then dielectric relaxation and fluorescence intensity experiments were carried out. The diffusion coefficient of the solution with a weight fraction of HPMC being 0.06 could be extrapolated to zero at the cloud-point curve which showed the criticality of the solution. The fluorescence intensity increased at a temperature much lower than the cloud point and the gel point, especially for concentrated solutions, indicating the hydrophobic interaction as the driving force of the gelation coupled by the phase separation. Dielectric relaxation measurements by time-domain reflectometry revealed two characteristic relaxations of chain motions around 100 MHz and orientation of free water around 20 GHz , which is accompanied by a low-frequency tail reflecting hydration water.

Effect of nicotinamide on the properties of aqueous HPMC solutions

The effect of nicotinamide on the properties of aqueous hydroxypropylmethylcellulose (HPMC) solutions was studied. Rheological studies showed that solutions of HPMC of concentration less than 3.0 w/v.% did not form gels and exhibited Newtonian flow patterns at 25 °C. The inclusion of nicotinamide increased the viscosity of HPMC solutions, which indicates that nicotinamide expanded the HPMC coils in aqueous solution. When the temperature of the solutions was raised, they formed gels that were detected by viscometry and oscillation tests as abrupt increases in viscosity, storage modulus and loss modulus and an abrupt decrease in loss angle. Nicotinamide exhibited a salting in effect on the HPMC solutions resulting in an increase in gelation temperatures and cloud points. These effects are considered to be due to the hydrogen-bonding of nicotinamide to HPMC molecules, which was suggested by a shift to a longer wavelength of the UV spectra of aqueous nicotinamide solutions by the addition of HPMC. These results suggested that nicotinamide has affinity with the hydrophilic groups of HPMC.