Influence of process parameters on fluidised hot-melt granulation and tablet pressing of pharmaceutical powders

This study investigates the influence of process parameters on the fluidised hot melt granulation of lactose and PEG 6000, and the subsequent tablet pressing of the granules. Granulation experiments were performed to assess the effect of granulation time and binder content of the feed on the resulting granule properties such as mass mean granule size, size distribution, granule fracture stress, and granule porosity. These data were correlated using the granule growth regime model. It was found that the dominant granule growth mechanisms in this melt granulation system were nucleation followed by steady growth (PEG 10–20% w/w). However, with binder contents greater than 20% w/w, the granulation mechanism moved to the “over-wet massing” regime in which discrete granule formation could not be obtained. The granules produced in the melt fluidised bed process were subsequently pressed into tablets using an industrial tablet press. The physical properties of the tablets: fracture stress, disintegration time and friability were assessed using industry standards. These analyses indicated that particle size and binder content of the initial granules influenced the mechanical properties of the tablets. It was noted that a decrease in initial granule size resulted in an increase in the fracture stress of the tablets formed.

Co-melt fluidised bed granulation of pharmaceutical powders: Improvements in drug bioavailability

This study investigates the use of co-melt fluidised bed granulation for the agglomeration of model pharmaceutical powders, namely, lactose mono-hydrate, PEG 10000, poly-vinyl pyrolidone and ibuprofen as a model drug. Granulation within the co-melt system was found to follow a nucleationâ??steady growthâ??coating regime profile. Using high molecular weight PEG binder, the granulation mechanism and thus the extent of granulation was found to be significantly influenced by binder viscosity. The compression properties of the granulate within the hot fluidised bed were correlated using a novel high temperature experimental procedure. It was found that the fracture stress and fractural modulus of the materials under hot processing conditions were orders of magnitude lower than those measured under ambient conditions. A range of particle velocities within the granulator were considered based on theoretical models. After an initial period of nucleation, the Stokes deformation number analysis indicated that only velocities within the high shear region of the fluidised bed were sufficient to promote significant granule deformation and therefore, coalescence. The data also indicated that larger granules de-fluidised preventing agglomeration by coalescence. Furthermore, experimental data indicated that dissipation of the viscous molten binder to the surface was the most important factor in the latter stages of the granulation process. From a pharmaceutical perspective the inclusion of the model drug, ibuprofen, combined with PVP in the co-melt process proved to be highly significant. It was found that using DSC analysis on the formulations that the decrease in the heat of fusion associated with the melting of ibuprofen within the FHMG systems may be attributed to interaction between PVP and ibuprofen through inter-molecular hydrogen bonding. This interaction decreases the crystallinity of ibuprofen and facilitates solubilisation and bioavailability within the solid matrix.

A novel approach to dynamic modelling of polymer extrusion for improved process control

Polymer extrusion is a complex process and the availability of good dynamic models is key for improved system operation. Previous modelling attempts have failed adequately to capture the non-linearities of the process or prove too complex for control applications. This work presents a novel approach to the problem by the modelling of extrusion viscosity and pressure, adopting a grey box modelling technique that combines mechanistic knowledge with empirical data using a genetic algorithm approach. The models are shown to outperform those of a much higher order generated by a conventional black box technique while providing insight into the underlying processes at work within the extruder.

Enhancing process insight in polymer extrusion by grey box modelling

Due to the complexity and inherent instability in polymer extrusion there is a need for process models which can be run on-line to optimise settings and control disturbances. First-principle models demand computationally intensive solution, while ‘black box’ models lack generalisation ability and physical process insight. This work examines a novel ‘grey box’ modelling technique which incorporates both prior physical knowledge and empirical data in generating intuitive models of the process. The models can be related to the underlying physical mechanisms in the extruder and have been shown to capture unpredictable effects of the operating conditions on process instability. Furthermore, model parameters can be related to material properties available from laboratory analysis and as such, lend themselves to re-tuning for different materials without extensive remodelling work.

Electrochemical synthesis and characterization of conducting polymers using room temperature melt as an electrolyte

Aromatic monomers can be polymerised using the chloroaluminate room temperature melt obtained by mixing 1:2 ratio of cetyl pyridinium chloride and anhydrous aluminium chloride miscible in all proportions with organic solvents as an electrolyte. The chloroaluminate (AlCl4-) anion generated in this melt having a tetrahedral symmetry with equal bond lengths and bond angles is the dopant to stabilize macrocation generated near the vicinity of anode to yield better conducting and better ordered electronically conducting free standing polymer film. In this communication, we discuss the polymers derived from benzene and pyrrole and their characterization by various techniques.

A new route to synthesize high degree polythiophene in a room temperature melt medium

Conducting polymers suffer from folds and kinks because of random nucleation and solvation of a free radical cation to yield a cross linked/disordered polymer and therefore a solvent free electrochemical polymerization in a room temperature melt medium is adopted to yield a high degree polymer with high electronic conductivity. Electropolymerization of thiophene was performed on platinum/ITO substrates using cyclic voltametry or galvenostatic mode in chloroaluminate room temperature melt medium to obtain a reddish brown free standing film which can be peeled off from the electrode surface after a minimum of 10 cycles. The conductivity was found to be around 102 S/cm. The degree of polymerization was calculated to be around 44 from IR studies. A layered structure supportive for high degree of polymerization was witnessed from potential step technique. From UV spectra the charge carriers were found to be bipolarons. The morphology of the film was found to be crystalline from SEM and XRD studies. Capacitative impedance properties for doped samples were interpreted from impedance spectroscopy.

Electrochemical synthesis and characterization of conducting polyparaphenylene using room-temperature melt as the electrolyte

Freestanding polyparaphenylene films were obtained on polymerization of benzene at potential of 1.2 V versus Al wire on substrates like platinum/transparent conducting glass as an anode. The electrolyte used was chloroaluminate room-temperature melt, which was prepared by intimate mixing of a 1:2 ratio of cetyl pyridinium chloride and anhydrous aluminum chloride to yield a viscous liquid. This liquid was miscible in all proportions with benzene and other aromatic hydrocarbons in all proportions at room temperature. The polyparaphenylene films deposited on platinum anode exhibited a prominent cyclic voltammetric peak at 0.7 V versus Al wire as reference electrode in chloroaluminate medium. The impedance spectra gave low charge transfer resistance. The diffused reflectance electronic spectra of the film gave the peaks at 386 nm and 886 nm. The PPP films showed electronic conductivity around 3–4 × 104 S/cm by four probe method under nitrogen atmosphere. The polymer was also characterized by IR spectra, thermal studies, and SEM studies.

Studies on polypyrrole film in room temperature melt

A bluish-black shining free standing polypyrrole film (PPy) of electronic conductivity 130 S cm-1 has been prepared by electrochemical oxidative polymerization of pyrrole on Pt/transparent glass conducting electrode resistance 15 O cm-1, using a room temperature melt as an electrolyte, composed of 1:3 stoichiometric ratio of cetyl pyridinium chloride and anhydrous aluminum chloride at 0.58 V versus Al wire as a reference electrode. The film possessed a charge transfer resistance of 132 O, and showed two absorption peaks at 457 and 1264 nm in the UV-vis–NIR diffused reflectance spectra. The morphology of the film was hexagonal. The potential step technique suggested a layered structure. This thin film can easily be peeled off from the electrode surface after three cycles and can be used for various applications like dissipation of electrostatic charge, battery electrode materials, solid electrolytic capacitor, electrochromic windows and displays, microactuators etc. It was also characterized by IR, thermal and SEM studies.