Continuous Shear Rheometry Research Articles

Rheological analysis of a novel phenylboronic acid-closomer gel

This study aims to characterize the rheological behavior of a novel phenylboronic acid (PBA)-based closomer nanoconjugate (Closogel) with potential application in pharmaceutical formulation. PBA was used as a cross-linking agent and model (antiviral) drug. The PBA loaded Closogel chemical structure was analyzed by boron (11B) NMR and Fourier transform infrared (FTIR) spectroscopy. The Closogel and control hydroxyethyl cellulose (HEC) gel were analyzed under oscillatory and continuous shear rheometry followed by mathematical modeling to characterize the gel flow behavior. The chemical analysis confirmed the existence of characteristic borate esters peaks and Boron chemical shifts within Closogel spectra. Due to its more flexible molecular structure, undiluted Closogel exhibited lower, yield stress, viscosity and relaxation time (30 Pa &163 Pa.s & 0.21 s vs 45 Pa &301 Pa.s & 0.39 s for HEC). Both Closogel and HEC gels exhibited a thixotropic behavior. The plastic undiluted and pseudoplastic 2.5 % w/v aqueous Closogels were more viscous than elastic (tan (δ) > 1) in the linear viscoelastic range. The Herschel-Bulkley model showed a significant fitting to all experimental data (R2 > 0.95). The 0.25 % w/v aqueous Closogel nearly exhibited a Newtonian behavior with a flow index of 0.93. These data suggest that PBA loaded Closomer-based gels have similar rheological behavior, with lower complex modulus than that of HEC gels, and they can be a promising platform used for delivery of topical antiviral or other bioactive agents.

Curcumin-Loaded Liquid Crystalline Systems for Controlled Drug Release and Improved Treatment of Vulvovaginal Candidiasis

Vulvovaginal candidiasis (VVC) is the most common infection caused by Candida albicans and greatly reduces the quality of life of women affected by it. Due to the ineffectiveness of conventional treatments, there is growing interest in research involving compounds of natural origin. One such compound is curcumin (CUR), which has been proven to be effective against this microorganism. However, some of CUR's physicochemical properties, especially its low aqueous solubility, make the therapeutic application of this compound difficult. Thus, the incorporation of CUR in mucoadhesive liquid crystalline systems (MLCSs) for vaginal administration may be an efficient strategy for the treatment of VVC. MLCSs are capable of potentiating the compound's action, releasing it in a controlled manner, and can enable longer exposure at the site of infection. In this study, MLCSs consisting of oleic acid and ergosterol 5:1 (w/w) as the oily phase, PPG-5-CETETH-20 as the surfactant, and a polymer dispersion of 1% chitosan as the aqueous phase, were developed for the application of CUR (MLCS-CUR) in VVC treatment. The formulations were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), oscillatory rheometry, continuous shear rheometry, texture profile analysis, and in vitro mucoadhesion. In addition, the antimicrobial activity was evaluated in vitro, and the effects on local fungal burden and cytokine profiles were investigated in a murine model of VVC. PLM and SAXS showed that the developed formulations presented a characteristic of a microemulsion. However, after the addition of artificial vaginal mucus (AVM), PLM showed that the formulations had structures similar to the "Maltese cross" characteristic of lamellar MLCS. Mucoadhesive test results showed an increase in the mucoadhesive strength of these formulations. Rheology analyses suggested long-lasting action of the formulation at the infected site. The in vitro antimicrobial activity assays suggested that CUR possesses antifungal activity against Candida albicans, determined after its incorporation into the MLCS. Further, MLCS-CUR was also more effective in vivo in the control of vaginal infection than treatment with fluconazole. Immunological assays showed that the ratio of pro-inflammatory (IL-1β) to anti-inflammatory (TGF-β) cytokines has decreased and that there is a reduction in the number of polymorphonuclear neutrophils recruited to the vaginal lumen, showing that treatment with MLCS-CUR was effective in modulating the inflammatory reaction associated with the infection. The results suggest that MLCSs could potentially be used in the treatment of VVC with CUR.

Rheological destructuring of aqueous gels composed of cellulose ethers following storage in the presence of redox agents

AbstractDespite their widespread use, there is a paucity of information concerning the effect of storage on the rheological properties of pharmaceutical gels that contain organic and inorganic additives. Therefore, this study examined the effect of storage (1 month at either 4 or 37°C) on the rheological and mechanical properties of gels composed of either hydroxypropylmethylcellulose (3–5% w/w, HPMC) or hydroxyethylcellulose (3–5% w/w, HEC) and containing or devoid of dispersed organic (tetracycline hydrochloride 2% w/w) or inorganic (iron oxide 0.1% w/w) agents. The mechanical properties were measured using texture profile analysis whereas the rheological properties were analyzed using continuous shear rheometry and modeled using the Power Law model. All formulations exhibited pseudoplastic flow with minimal thixotropy. Increasing polymer concentration (3–5% w/w) significantly increased the consistency, hardness, compressibility, and adhesiveness of the formulations due to increased polymer chain entanglement. Following storage (1 month at 4 and 37°C) the consistency and mechanical properties of additive free HPMC gels (but not HEC gels) increased, due to the time‐dependent development of polymer chain entanglements. Incorporation of tetracycline hydrochloride significantly decreased and increased the rheological and mechanical properties of HPMC and HEC gels, respectively. Conversely, the incorporation of iron oxide did not affect these properties. Following storage, the rheological and mechanical properties of HPMC and HEC formulations were markedly compromised. This effect was greater following storage at 37 than at 4°C and, additionally, greater in the presence of tetracycline hydrochloride than iron oxide. It is suggested that the loss of rheological/mechanical structure was due to chain depolymerization, facilitated by the redox properties of tetracycline hydrochloride and iron oxide. These observations have direct implications for the design and formulation of gels containing an active pharmaceutical ingredient. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 852–859, 2005

Steady flow and viscoelastic properties of lubricating grease containing various thickener concentrations

The flow and viscoelastic properties of a lubricating grease formed from a thickener composed of lithium hydroxystearate and a high-boiling-point mineral oil were investigated as a function of thickener concentration. The flow properties of grease were measured using continuous shear rheometry, while the viscoelastic properties were measured using oscillatory shear measurements. The flow properties show that grease is a shear-thinning fluid with a yield stress that increases with thickener concentration. At concentrations of lithium hydroxystearate greater than 5% by volume, the storage modulus, G′, was found to be greater than the loss modulus, G″, with both moduli increasing with increasing thickener concentration, below this critical concentration G″ was greater than G′. Slip at the wall of the measuring platens was a major problem encountered during the rheological measurement of grease, this is hardly surprising, and greases are designed to slip in their lubricating functions. Therefore the measuring platens were roughened by sandblasting and significantly higher yield values were recorded with the roughened geometries. Creep experiments were also performed. In the creep test, yield stresses of greases could be obtained. Zero shear viscosity was also calculated from the creep experiment and as a result viscosities over nine orders of magnitude were obtained. The power law index of the scaling law of the elastic modulus and yield stress with increasing volume fraction was found to be 4.7±0.2 suggesting that the flocculation of the particles that compose the grease is likely to be of the chemically limited aggregation variety.

Investigation on the viscoelastic properties of lipid based colloidal drug carriers

The rheological behaviour of solid lipid nanoparticle dispersions (SLN) prepared by high pressure homogenization was investigated using a Haake RS-100 rheometer. Four preparations differing in their lipid content and macroscopic consistency were tested by continuous shear rheometry and oscillatory testing. Rheological data from continuous shear measurement reveal plastic flow for systems with low lipid content as well as for systems with high lipid content. By using oscillatory testing more detailed information concerning the structure could be achieved. Rheological measurements of 40% lipid dispersions show viscoelastic properties comparable to the data from standard dermal preparations. Therefore high concentrated lipid dispersions might constitute a promising vehicle for topical administration.

An investigation into interactions between polyacrylic polymers and a non-ionic surfactant: an emulsion preformulation study

The aim of this study was to investigate possible interactions between a polymeric emulsifier and a non-ionic surfactant, with a view of achieving better understanding of emulsion stabilisation mechanisms. The polymeric emulsifier used was acrylates/C 10–30 alkyl acrylate crosspolymer (Pemulen TR-2®), while Polyoxyethylene 20 sorbitan mono-oleate (Polysorbate 80) has been chosen as a model surfactant. Both materials were used within the concentration range relevant for their practical application. A 0.2%w/w aqueous dispersion of polymeric emulsifier, containing various amounts of surfactant (from 0.01 to 1.0% w/w) was used throughout the study. Interfacial aspects of the proposed polymer/surfactant interactions were analysed by means of surface tension measurements. Changes in the network structure of the test dispersions were quantified by continuous shear rheometry, supported by the texture analysis. To analyse the influence of hydrophobic alkyl groups present on the Pemulen TR-2® chains, an unmodified, hydrophilic polyacrylic acid polymer, Carbopol 934P®, was assessed under the same conditions. The results obtained by both surface tension and rheological studies have revealed large differences in behaviour of the two polymers in the presence of the model surfactant. Pemulen TR-2® was shown to desorb the surfactant from the surface, within the whole concentration range studied. Furthermore, an increase in viscosity and texture profile parameters with increasing Polysorbate 80 concentration up to 0.3% w/w was evident in the case of Pemulen TR-2® dispersions. This was followed by a decrease in the gel network strength at higher surfactant concentrations. On the other hand, Carbopol 934P® has shown no signs of surfactant desorption and only small changes in the network structure with the increasing concentration of surfactant. It is shown in this study that an interaction between a polymeric emulsifier Pemulen TR-2® and a non-ionic surfactant Polysorbate 80 does occur in their aqueous dispersion, and that it is: (a) hydrophobic in nature; (b) concentration-dependent; and (c) has an impact on the rheological properties of dispersion.

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.

US 4,923,916 & US 4,923,917 Fire retardants for polystyrene and sma

Liquid paraffin emulsions stabilized by sodium dodecyl sulfate with long-chain alcohols have been examined by microscopy, particle-size analysis, continuous shear rheometry, and creep. The disperse phases were aggregated and emulsions were viscoelastic and thixotropic and developed crystals on storage. Emulsions were firm and rheologically stable when cetostearyl alcohol was used. They were similar but slightly less stable when formulated with (a) a mixture of C16 and C18 alcohols in the ratio present in cetostearyl alcohol and (b) a mixture of C10, C12, C14, C16, and C18 alcohols in similar ratios. Emulsions were less stable when formulated either with C16 or with mixtures of C16 and C18 alcohols in ratios 31, 11, and 13. A more mobile, less stable emulsion was obtained with C18 alone, but a stiff emulsion was formed provided that the ratio of C16 to total alcohol (C16 plus C18) was greater than approximately 0.07. Differences between emulsions were not related to particle-size distribution but to the nature and content of the C18 alcohol, which influenced the strength of the viscoelastic network formed. Trace amounts of unidentified compounds exerted a minor effect.

Continuous shear rheometry of o/w emulsions; control of evaporation in cone/plate geometry

Volatile solvents may evaporate during cone/plate viscometry so that false rheograms develop. This surface evaporation was prevented in a cod-liver oil-in-water emulsion stabilized with zanthoxylum gum by layering a film of cod-liver oil on the exposed surface of the emulsion test sample. The oil layer effectively prevented evaporation and did not alter significantly the rheological behaviour of the test material.

Formation of liquid crystals in sunflower oil in water emulsions

Sunflower oil in water emulsions containing between 10–70% (w/w) oil and 1–15% (w/w) sorbitan monopalmitate (Span 40) and polyoxyethylene (20) sorbitan monopalmitate (Tween 40) in different ratios were prepared. Their rheological behavior was investigated by continuous shear rheometry and by creep viscometry. Emulsions containing ⩾5% (w/w) of Span Tween in weight ratios of 6 4 and 7 3 exhibited viscoelasticity. This was ascribed to the presence of a lamellar type of liquid crystalline phase in the systems which was confirmed by electron microscopy.

The rheological properties of carbopol gels I. Continuous shear and creep properties of carbopol gels

The effect of physical and chemical variables on consistency of Carbopol 940 and 941 gels was investigated by continuous shear rheometry. Gels provided plastic flow curves with negligible hysteresis. Continuous shear properties were not greatly affected by centrifuging, milling, temperature cycling, and ageing. Initial addition of neutralizing agent (0–6% w/w for 3% gels) markedly increased consistency; further addition caused a more gradual increase. Daylight reduced consistency. Apparent viscosities varied exponentially with concentration. Increased temperature gradually decreased apparent viscosity. Solvents had a variable effect on apparent viscosities which could not be correlated with solvent viscosity nor molecular weight. Apparent viscosities for gels neutralized with different bases were independent of type of base used.Small strain testing investigated fundamental properties of Carbopol gels and determined the effect of polymer concentration, temperature, neutralization, different solvents and neutralizers. Gels were linear viscoelastic and to a first approximation were elastic solids. Creep compliance varied exponentially with concentration and showed no correlation with solvent or neutralizer type.

Kinetics of structure build-up in self bodied emulsions stabilized by mixed emulsifiers

Ternary systems and emulsions prepared with anionic (sodium dodecyl sulfate), cationic (cetrimide), or nonionic (cetomacrogol) surfactants and cetostearyl alcohol were examined in creep and in continuous shear rheometry at the storage temperature of 25°C. Systems were tested frequently during the first 24 hr after preparation, and then regularly for 3 months. Creep tests were of short duration and the curves were analyzed to derive continuous spectra of retardation times. For each surfactant, the results obtained were correlated with the mechanisms by which gel networks formed. With age, anionic and cationic ternary systems and emulsions behaved similarly with respect to total compliances, retardation spectra, and continuous shear parameters. Additional structure, although not extensive, formed within the first 2 hr storage. This was indicated in creep by initial falls in total compliance values and decreases in the heights of retardation spectra, and in continuous shear by corresponding increases in apparent viscosities and hysteresis loop areas. Thereafter negligible new structure formed, and thus retardation spectra for systems tested after 2.5 and 24 hr storage were similar, and there was little variation in total compliance, apparent viscosity, and loop area values. The essentially constant position of maxima in the retardation spectra indicated that the high temperature interaction which occurred during the preparation of ionic systems was the major mechanism which operated to form gel networks. The low temperature interaction occurring during the first 2 hr storage was insignificant. Cetomacrogol ternary system and emulsion behaved differently to the ionic systems. Structure built up rapidly during the first 24 hr storage. This was shown in creep by marked reductions in total compliances and retardation spectral values and in continuous shear by changing complex flow properties. The movement of maxima in the retardation spectra to longer times indicated that the mechanisms which operated to form gel networks at the storage temperature produced structures which differed at a molecular level to those formed at high temperatures.

Kinetics of structure build-up in self-bodied emulsions stabilized by mixed emulsifers.

Journal Article Kinetics of structure build-up in self-bodied emulsions stabilized by mixed emulsifiers Get access B W BARRY, B W BARRY School of Pharmacy, Portsmouth Polytechnic, Park Road, Portsmouth, PO1 2QQ, UK Search for other works by this author on: Oxford Academic Google Scholar G M SAUNDERS G M SAUNDERS School of Pharmacy, Portsmouth Polytechnic, Park Road, Portsmouth, PO1 2QQ, UK Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 23, Issue Supplement_1, December 1971, Page 240S, https://doi.org/10.1111/j.2042-7158.1971.tb08827.x Published: 12 April 2011

The self-bodying action of alkyltrimethylammonium bromides/cetostearyl alcohol mixed emulsifiers; Influence of quaternary chain length

Liquid paraffin in water emulsions stabilized by alkyltrimethylammonium bromides (of C 12C 18 chain lengths) with cetostearyl alcohol have been examined by microscopy, particle size analysis, continuous shear rheometry, and creep. The rheological properties of emulsions prepared from each quaternary mixed emulsifier were related to gel networks formed in the continuous phases. These networks were shown to have properties similar to those of ternary systems formed by dispersing the corresponding quaternary surfactants and cetostearyl alcohol in water. All four quaternary mixed emulsifiers exhibited the self-bodying phenomenon. Ternary systems and emulsions of equivalent mixed emulsifier concentration increased in consistency as the surfactant chain length increased. Emulsions prepared with quaternaries of medium chain length (C 14 and C 16) formed strong viscoelastic networks. C 12 emulsions possessed tenuous networks and when C 18 quaternary was used, the structures were not as rigid as predicted by the trend of the lower homologs. When C 12 and C 18 emulsions were stored, oil globules which were hexagonal in cross section were formed. These reverted to a spherical shape when diluted. These results are discussed at a molecular level by considering the effect of variation in surfactant chain length on the formation of smectic structures.

The self-bodying action of the mixed emulsifier cetrimide-cetostearyl alcohol.

Liquid paraffin emulsions stabilized by the mixed emulsifier cetrimide/cetostearyl alcohol have been examined by microscopy, particle size analysis, continuous shear rheometry, and creep. The disperse phase of each emulsion was aggregated, and many of the nonspherical particles contained crystals of cetostearyl alcohol. The rheological properties of each emulsion were not related directly to the particle size distribution but to a gel network present in the continuous phase. This gel network was shown to be similar to that formed by dispersing cetrimide and cetostearyl alcohol in water so as to form a ternary system. All the systems showed complex flow properties in continuous shear experiments, e.g., hysteresis loops denoting irreversible shear breakdown. Additional complex flow properties, i.e., spur points and dilatancy, apparent in emulsions containing greater than 5% mixed emulsifier, were related to the structure in the continuous phase. In creep, mechanical models of three Voigt Units in series with a Maxwell Unit were deduced. In ternary systems and emulsions, the compliances decreased and the viscosities increased as the cetrimide/cetostearyl alcohol concetration increased. The creep parameters indicated that emulsions containing greater than 5% mixed emulsifier increased in consistency on aging, owing to the orientation of gel structure in the continuous phase.

Rheology of emulsions stabilized by sodium dodecyl alcohols

Liquid paraffin emulsions stabilized by sodium dodecyl sulfate with long-chain alcohols have been examined by microscopy, particle-size analysis, continuous shear rheometry, and creep. The disperse phases were aggregated and emulsions were viscoelastic and thixotropic and developed crystals on storage. Emulsions were firm and rheologically stable when cetostearyl alcohol was used. They were similar but slightly less stable when formulated with (a) a mixture of C16 and C18 alcohols in the ratio present in cetostearyl alcohol and (b) a mixture of C10, C12, C14, C16, and C18 alcohols in similar ratios. Emulsions were less stable when formulated either with C16 or with mixtures of C16 and C18 alcohols in ratios 31, 11, and 13. A more mobile, less stable emulsion was obtained with C18 alone, but a stiff emulsion was formed provided that the ratio of C16 to total alcohol (C16 plus C18) was greater than approximately 0.07. Differences between emulsions were not related to particle-size distribution but to the nature and content of the C18 alcohol, which influenced the strength of the viscoelastic network formed. Trace amounts of unidentified compounds exerted a minor effect.

The self bodying action of the mixed emulsifier sodium dodecyl sulfate/cetyl alcohol

Liquid paraffin emulsion stabilized by the mixed emulsifier sodium dodecyl sulfate/cetyl alcohol have been examined by microscopy, particle size analysis, continuous shear rheometry, and creep. The disperse phase was aggregated and included some nonspherical globules containing crystals of cetyl alcohol. Emulsions were thixotropic and the extent increased with emulsifier concentration. In creep, systems suggested a mechanical model of three Voigt units in series with a Maxwell unit; the compliances decreased and the viscosities increased with emulsifier concentration. Rheological properties are explained by the presence of a viscoelastic network in the continuous phase.