The rheological properties of wet powder masses used in the preparation of pharmaceutical pellets by extrusion/spheronization were evaluated utilizing capillary and rotational rheometers. A ram extruder was used as a capillary rheometer to construct flow and viscosity curves for each wet mass under different extrusion rates and die geometry. As a result, shear thinning behavior was observed for all wet masses. Among the considered rheological models Power Law and Herschel-Bulkley models fitted well with the experimental results. For the majority of the wet masses, water separation and migration occurred during extrusion which led to uneven water content in the extrudate. The effect of extrusion condition including extrusion speed, die geometry and water content on the occurrence of water separation was investigated and the surface quality of the extrudates was compared. In addition, dynamic rheometry tests were done by a parallel plate rheometer to investigate the viscoelastic properties of the wet masses. The frequency sweep tests showed that as water content of the wet masses decreases storage (G') and loss modulus (G″) increase. The storage modulus values were much higher than those of the loss modulus showing dominated elastic rather than viscous behavior for the wet masses at low deformation rates.
PURPOSE: In the present study we evaluated a novel processing technique for the continuous production of hotmelt extruded controlled release matrix systems. A cutting technique derived from plastics industry, where it is widely used for cutting of cables and wires was adapted into the production line. Extruded strands were shaped by a rotary-fly cutter. Special focus is laid on the development of a process analytical technology by evaluating signals obtained from the servo control of the rotary fly cutter. The intention is to provide a better insight into the production process and to offer the ability to detect small variations in process-variables. MATERIALS AND METHODS: A co-rotating twin-screw extruder ZSE 27 HP-PH from Leistritz (Nürnberg, Germany) was used to plasticize the starch; critical extrusion parameters were recorded. Still elastic strands were shaped by a rotary fly-cutter type Dynamat 20 from Metzner (Neu-Ulm, Germany). Properties of the final products were analyzed via digital image analysis to point out critical parameters influencing the quality. Important aspects were uniformity of diameter, height, roundness, weight and variations in the cutting angle. Stability of the products was measured by friability tests and by determining the crushing strength of the final products. Drug loading studies up to 70% were performed to evaluate the capacity of the matrix and to prove the technological feasibility. Changes in viscosities during API addition were analyzed by a Haake Minilab capillary rheometer. X-ray studies were performed to investigate molecular structures of the matrices. RESULTS: External shapes of the products were highly affected by die-swelling of the melt. Reliable reproducibility concerning uniformity of mass could be achieved even for high production rates (>2500 cuts/min). Both mechanical strength and die swelling of the products could be linked to the ratio of amylose to amylopectin. Formulations containing up to 70% of API could still be processed. Viscosity measurements revealed the plasticizing effect caused by API addition. Dissolution data proved the suitability of extruded starch matrices as a sustained release dosage form. Monitoring of consumed energies during the cutting process could be linked to changes in viscosity. The established PAT system enables the detection of small variations in material properties and can be an important tool to further improve process stability.
When hagfish (Myxinidae) are attacked by predators, they form a dilute, elastic, and cohesive defensive slime made of mucins and protein threads. In this study we propose a link between flow behavior and defense mechanism of hagfish slime. Oscillatory rheological measurements reveal that hagfish slime forms viscoelastic networks at low concentrations. Mucins alone did not contribute viscoelasticity, however in shear flow, viscosity was observed. The unidirectional flow, experienced by hagfish slime during suction feeding by predators, was mimicked with extensional rheology. Elongational stresses were found to increase mucin viscosity. The resulting higher resistance to flow could support clogging of the attacker’s gills. Shear flow in contrast decreases the slime viscosity by mucin aggregation and leads to a collapse of the slime network. Hagfish may benefit from this collapse when trapped in their own slime and facing suffocation by tying a sliding knot with their body to shear off the slime. This removal could be facilitated by the apparent shear thinning behavior of the slime. Therefore hagfish slime, thickening in elongation and thinning in shear, presents a sophisticated natural high water content gel with flow properties that may be beneficial for both, defense and escape.
Delivery of tissue glues through small-bore needles or trocars is critical for sealing holes, affixing medical devices, or attaching tissues together during minimally invasive surgeries. Inspired by the granule-packaged glue delivery system of sandcastle worms, a nanoparticulate formulation of a viscous hydrophobic light-activated adhesive based on poly(glycerol sebacate)-acrylate is developed. Negatively charged alginate is used to stabilize the nanoparticulate surface to significantly reduce its viscosity and to maximize injectability through small-bore needles. The nanoparticulate glues can be concentrated to ≈30 w/v% dispersions in water that remain localized following injection. With the trigger of a positively charged polymer (e.g., protamine), the nanoparticulate glues can quickly assemble into a viscous glue that exhibits rheological, mechanical, and adhesive properties resembling the native poly(glycerol sebacate)-acrylate based glues. This platform should be useful to enable the delivery of viscous glues to augment or replace sutures and staples during minimally invasive procedures.
Real time measurement of melt rheology has been investigated as a Process Analytical Technology (PAT) to monitor hot melt extrusion of an Active Pharmaceutical Ingredient (API) in a polymer matrix. A developmental API was melt mixed with a commercial copolymer using a heated twin screw extruder at different API loadings and set temperatures. The extruder was equipped with an instrumented rheological slit die which incorporated three pressure transducers flush mounted to the die surface. Pressure drop measurements within the die at a range of extrusion throughputs were used to calculate rheological parameters such as shear viscosity and exit pressure, related to shear and elastic melt flow properties respectively. Results showed that the melt exhibited shear thinning behavior whereby viscosity decreased with increasing flow rate. Increase in drug loading and set extrusion temperature resulted in a reduction in melt viscosity. Shear viscosity and exit pressure measurements were found to be sensitive to API loading. These findings suggest that this technique could be used as a simple tool to measure material attributes in-line, to build better overall process understanding for hot melt extrusion.
Shear and extensional deformation are two basic rheological phenomena which occur commonly in our daily life. Because of the very different nature of the two deformations, fluid materials may exhibit significant differences in their responses to shear and extensional forces. This work investigated the human perception of shear and extensional viscosity and tested the hypothesis that human have different discriminatory sensation mechanisms including scaling to the two deformations. A series of fluid samples were prepared using two common food thickeners, guar gum and sodium carboxylmethylcellulose (CMC-Na). The shear and extensional flow behavior of these fluids were assessed using shear and extensional rheometers and in addition two separate sensory analysis sessions were organized to assess human sensitivity in perceiving the two viscosities. Magnitude estimation was used in the first session to assess human sensitivity in the perception of the shear and extensional viscosities and just-noticeable-difference (JND) assessment was used for the second session to identify the typical threshold of viscosity discrimination. For the participants considered, it was found that the perception of both shear and extensional viscosity follow a power law relationship i.e. Steven’s law. It was also observed that the human has a greater discriminatory capacity in perceiving extensional viscosity. JND analysis showed that the human threshold in detecting shear viscosity difference was 9.33%, but only 6.20% for extensional viscosity.
Evolution of bubbles is the key to volume development in bread dough. The influence of wheat bran on bubble growth in bread dough through the mixing, fermentation, and proofing stages is described as a function of its level of addition. Confocal laser scanning microscopy in combination with image processing tools was used to obtain the bubble size and shape parameters. The relationship between bubble behavior and dough rheology was mapped using biaxial extension and dynamic oscillatory rheometry studies. With increase in level of bran addition, mean bubble size decreased corresponding to each stage and showed an inverse relationship with dough overpressure and elastic modulus. Addition of wheat bran was observed to suppress the bubble coarsening phenomenon in dough. Experimental observations indicated the plausibility of coalescence-mediated bubble growth in bread dough during the latter stages of fermentation and proofing, which was hindered in the presence of bran particles.
An important parameter for the performance of nanomaterials is the degree by which the nanoparticles are dispersed in a matrix. Optical microscopy or scattering methods are useful to characterise the state of dispersion, but are not generally applicable to all materials. Electron microscopy methods are laborious in preparation and typically offer only quantitative information on a very local scale. In the present work we investigate how high frequency rheological measurements can be used for partially dispersed suspensions at intermediate to higher particle loadings, even for high viscous matrices. Although the contribution of the particles is particularly visible in the low frequency linear viscoelastic behaviour, a more direct relationship between rheological properties and degree of dispersion can be derived from the loss modulus in the high frequency limit. To this end, a home-built piezo shear rheometer is constructed to extend the frequency range typically accessible by commercial rotational rheometers. Measurements on spherical silica particles, with a varying degree of dispersion in low molecular weight PDMS, are used to demonstrate how high frequency rheometry can be used to quantify dispersion quality. The linear viscoelastic properties are compared to analytical scaling theories to demonstrate that a hydrodynamically dominated regime is reached. The dependence of the relative high frequency loss modulus on volume fraction is then compared to predictions of a hydrodynamic viscosity model for the derivation of a dispersion quality index. It is used to follow the evolution of the dispersion quality as a function of mixing time and consumed power.
- Langmuir : the ACS journal of surfaces and colloids
- Published 5 months ago
We study the kinetics of bitumen emulsion destabilization after addition of sodium hydroxide (NaOH) using macroscopic observations and rheology. Destabilization occurs in a two step process: first emulsion flocculates forming a percolated network of contacting drops and then coalescence provokes the irreversible connection of bitumen drops leading to a bitumen continuous network that further relaxes the shape. We show that the destabilization kinetics exhibits a rheological easily identifiable signature allowing reproducible and accurate measurement of the connection/coalescence time trc (which corresponds to the time, determined by rheology, required to form the network made of drops connected by non relaxed coalescence). Using this powerful tool, we show that, even if viscosity is thought to govern the shape relaxation of the connected network it does not determine the connection kinetics. Indeed emulsions with similar rheological behaviors exhibit very different destabilization times. Instead, we evidence a good correlation between the bitumen crystallized wax content and trc. From these experimental results we discuss the stabilizing effect against coalescence of crystals in bitumen emulsions.
Whereas most of lipids have viscous properties and they do not have significant elastic features, ceramides behave as very rigid solid assemblies, displaying viscoelastic behaviour at physiological temperatures. The present review addresses the surface rheology of lipid binary mixtures made of sphingomyelin and ceramide. However, ceramide is formed by the enzymatic cleavage of sphingomyelin in cell plasma membranes. The consequences of the enzymatically-driven ceramide formation involve mechanical alterations of the embedding membrane. Here, an increase on surface shear viscosity was evidenced upon enzymatic incubation of sphingomyelin monolayers. The overall rheological data are discussed in terms of the current knowledge of the thermotropic behaviour of ceramide-containing model membranes.