Philip D. Coates

Cocrystalization and Simultaneous Agglomeration Using Hot Melt Extrusion

ABSTRACTPurposeTo explore hot melt extrusion (HME) as a scalable, solvent-free, continuous technology to design cocrystals in agglomerated form.MethodsCocrystal agglomerates of ibuprofen and nicotinamide in 1:1 ratio were produced using HME at different barrel temperature profiles, screw speeds, and screw configurations. Product was characterized for crystallinity by XRPD and DSC, while the morphology was determined by SEM. Dissolution rate and tabletting properties were compared with ibuprofen.ResultsProcess parameters significantly affected the extent of cocrystallization which improved with temperature, applied shear and residence time. Processing above eutectic point was required for cocrystallization to occur, and it improved with mixing intensity by changing screw configuration. Product was in the form of spherical agglomerates, which showed directly compressible nature with enhanced dissolution rate compared to ibuprofen. This marks an important advantage over the conventional techniques, as it negates the need for further size modification steps.ConclusionsA single-step, scalable, solvent-free, continuous cocrystallization and agglomeration technology was developed using HME, offering flexibility for tailoring the cocrystal purity. HME being an established technology readily addresses the regulatory demand of quality by design (QbD) and process analytical technology (PAT), offering high potential for pharmaceuticals.

Melt temperature field measurement in single screw extrusion using thermocouple meshes

The development and validation of a sensor for extrusion melt temperature field measurement is described. A grid of opposing thermocouple wires was constructed and held in position by a supporting frame. Wires were joined together at crossing points to form thermocouple junctions, which were computer monitored. The mesh was used to monitor melt temperature fields during single screw extrusion at the die entrance. Design and construction of the mesh is described in addition to experimental optimization of wire diameter and junction forming. Calibration of the sensor and potential measurement errors including shear heating effects are discussed. Initial results from single screw extrusion are presented for a commercial grade of low density polyethylene using five- and seven-junction thermocouple meshes. The dependence of melt temperature profile on screw speed is illustrated. At low screw speeds melt temperature profiles were flat in shape and higher than set wall temperatures. At higher screw speeds the profiles became more pointed in shape. Use of higher resolution sensors exposed more complex temperature profiles with shoulder regions.

Gas assisted injection moulding: Finite element modelling and experimental validation

Abstract Gas assisted injection moulding of a rectangular cross-section tensile test specimen has been modelled using a finite element implementation of the pseudo-concentration method, in which the velocity components and pres sure are interpolated as primitive variables. Two-dimensional and three- dimensional modelling formulations are presented and in each case wall thickness predictions are compared with actual measurements taken from specimens obtained from computer monitored gas assisted injection moulding production. Two different boundary conditions were used for the injection of gas into the cavity. Initial mechanical testing is used to compare the apparent elastic modulus of the solid material in gas assisted injection moulding specimens with that in solid polymer specimens.

Shear and extensional rheology of hydroxypropyl cellulose melt using capillary rheometry

With increasing interest in hot melt extrusion for preparing polymer-drug systems, knowledge of the shear and extensional rheology of polymers is required for the formulation and process design. Shear and extensional rheology of three commercial grades of hydroxypropyl cellulose (HPC) was examined at 140, 145 and 150 degrees C using twin bore capillary rheometry at range of processing rates. The power law model fitted for shear flow behaviour up to shear strain rates of approximately 1000s(-1), above which measured shear viscosities deviated from the power law and surface instabilities were observed in the extrudate, particularly for higher molecular weight grades. Shear thinning index was found to be relatively independent of temperature and molecular weight, whilst the consistency index, indicative of zero shear viscosity increased exponentially with increase in molecular weight. Extensional viscosity of all grades studied was found to decrease with increasing temperature and increasing processing rate. Foaming of the extrudate occurred especially at low temperatures and with the high molecular weight grade. An understanding of the relationships between shear and extensional flows with temperature, processing rate and molecular weight is a useful tool for process design; optimisation and troubleshooting of Hot melt extrusion (HME) of pharmaceutical formulations.

Stress measurements for contraction flows of viscoelastic polymer melts

The work presented in the second of a series of three papers providing a comprehensive in-process study of polyolefin melt flows through the convergent section of slit dies. Here we focus on stress fields developed in several linear and branched polyolefin melts. Accurate measurement of stress optical coefficients derived from flow induced birefringence has enabled determination of shear and first normal stress difference fields in these polymers in an abrupt entry convergent flow geometry. The progression of stress growth with increase in melt flow rate is also described. The dimensionless stress ratio (centre line tensile stress to slit wall shear stress) has been identified as a quantity which correlates with the relative vortex size in the linear and branched polyolefins. Fully developed entry flows on melt passage into the slit section are also studied and reflect relaxation characteristics of each polymer.

Ultrasound : A virtual instrument approach for monitoring of polymer melt variables

Non-invasive ultrasound measurements are not currently widely used, due to limitations in high temperature transducer technology and signal processing. These have been addressed in the ultrasound program in our laboratory, where high frequency sampling using our own high temperature probes is now available. The need for high frequency sampling of the ultrasound signal to resolve measurements of transit time (and amplitude) to the required accuracy requires handling of large amounts of data, and in the case of actual polymer processing such as extrusion, data processing needs to be real time. A computer controlled system for the acquisition of such data is described here, with examples of the sensitivity of the measurements to a range of polymer melt process variables, including polymer composition and fillers, for extrusion and injection moulding processing.

Predicting the rheology of linear with branched polyethylene blends

A series of melt blended commercial linear and branched polyethylenes are used to explore the generality of blending laws. The measured relaxation modulus G(t), and zero shear viscosity η0 for each blend and blend fraction, have been compared with prediction for miscible blends, particularly using equations derived by Tsenoglou (1987). Plus or minus deviation between theory and measurement is dependent on the relative molecular weights of the blend components. We have found empirically that a generalised form of the blending law for G(t) and for η0, with a floating index C, provides an improved prediction of the blend fraction data. In particular the function defining C is non-symmetrical, from which we infer the significance of branching as well as molecular weight. The optimum value of the index differs for each of our blends, in the range 1.25 to 4, the variability being accounted for by the different degrees to which branched and linear polymers relax co-operatively in the melt. Blends of two near linear polymers do not fit the floating index prediction and conform more closely, though not precisely, to the original Tsenoglou rule.

Measuring the development of fibre orientation during the melt extrusion of short glass fibre reinforced polypropylene

Abstract In this paper we describe an investigation into the development of fibre orientation during melt extrusion through two convergent dies: a conical die and a slit die. The material used was a short glass fibre (aspect ratio = 24) reinforced polypropylene at two fibre weight fractions, 20% and 30%. The development of fibre orientation through the two convergent zones was measured in detail using sophisticated image analysis facilities developed in-house. It was found that the ‘pseudo-affine’ deformation model predicted the development of fibre orientation very well for both die configurations, in terms of the applied macroscopic elongational strains. The addition of a breaker plate placed in the barrel of the extruder, between the extruder screw and the convergent flow zones, was shown to produce the highest degree of fibre alignment in the extrudates, by introducing additional pre-orientation of the fibres. Mechanical measurements on the extrudates showed that for the very high degrees of fibre alignment attained, the bending modulus in the extrusion direction reached 90% of the theoretical maximum for the fibre aspect ratio used, and the crack resistance parallel to the preferred fibre direction remained high.

Flow visualisation of polymer melts in abrupt contraction extrusion dies : quantification of melt recirculation and flow patterns

This paper is the first part of a series of three in which we present experimental and analytical data covering the development of entry profiles, normal and shear stress fields, velocity fields and the in-process extensional viscosity measurement of branched and linear polyolefins. Here, we report accurate in-process measurements of the natural flow profiles of selected branched and linear polyolefins obtained from screw-driven extrusion flows through an abrupt contraction geometry. Recirculation areas, vortex centres and detachment lengths were quantified and their dependence on flow rate and process temperature studied. Significant recirculation areas were observed for the branched melts. Both the size and the development of these features were dependent on flow rate and temperature. Recirculation areas of the linear polymers were less prominent and independent of flow conditions. Correlation has been observed between rheological characteristics of the low density polyethylenes and their entry behaviour.

Water assisted injection moulding : development of insights and predictive capabilities through experiments on instrumented process in parallel with computer simulations

Abstract An idealised model of core-out in water assisted injection moulding (WAIM) is set up to isolate the effect of cooling by the water on the deposited layer thickness. Based on simulations, this is investigated for a specific case as a function of Pearson number and power law index. It is found that cooling significantly reduces the layer thickness to the extent that a change in the flow regime ahead of the bubble, from bypass to recirculating flow, is possible. For shear thinning melts with high temperature coefficient of viscosity, the simulations show very low layer thickness, which may indicate unfavourable conditions for WAIM. Although in the real moulding situation, other effects will be superimposed on those found here, the results provide new insights into the fundamentals of WAIM. Investigation of other effects characterised by Fourier and Reynolds numbers will be reported subsequently. Some early process measurement results from an experimental WAIM mould are presented. Reductions in residual wall thickness are observed as the water injection set pressure is increased and the duration of water bubble penetration through the melt is determined experimentally. The formation of voids within the residual wall is noted and observed to reduce in severity with increasing water injection pressure. The presence of such voids can be detected by the signature from an infrared temperatures sensor.