Direct observation of morphological development during the spin-coating of polystyrene-poly(methyl methacrylate) polymer blends

We present results of the direct observation, in real-space, of the phase separation of high molecular weight polystyrene and poly(methyl methacrylate) from ortho-xylene using our newly developed technique of high speed stroboscopic interference microscopy. Taking a fixed concentration (3 wt % in o-xylene) at a fixed composition (1:4 by weight) and by varying the rotational rate during the spin-coating process, we are able to observe the formation of a range of phase separated bicontinuous morphologies of differing length-scales. Importantly, we are able to show that the mechanism by which the final phase separated structure is formed is through domain coarsening when rich in solvent, before vitrification occurs and fixes the phase separated structure. The ability to directly observe morphological development offers a route toward controlling the length-scale of the final morphology through process control and in situ feedback, from a single stock solution. © 2013 Wiley Periodicals, Inc.

Directed phase separation of PFO:PS blends during spin-coating using feedback controlled in situ stroboscopic fluorescence microscopy

Uniform thin-films of polymer blends can be produced through spin-coating, which is used on an industrial scale for the production of light emitting diodes, and more recently organic photovoltaic devices. Here, we present the results of the direct observation, and control, over the phase separation of polystyrene and poly(9,9′-dioctylfluorene) during spin-coating using high speed stroboscopic fluorescence microscopy. This new approach, imaging the fluorescence, from a blend of fluorescent + non-fluorescent polymers allows for intensity to be directly mapped to composition, providing a direct determination of composition fluctuations during the spin-coating process. We have studied the compositional development and corresponding structural development for a range of compositions, which produce a range of different phase separated morphologies. We initially observe domains formed by spinodal decomposition, coarsening via Ostwald Ripening until an interfacial instability causes break-up of the bicontinuous morphology. Ostwald ripening continues, and depending upon composition a bicontinuous morphology is re-established. By observing compositional and morphological development in real-time, we are able to direct and control morphological structure development through control of the spin coating parameters via in situ feedback. © 2013 The Royal Society of Chemistry.

Functionalised particles using dry powder coating in pharmaceutical drug delivery:promises and challenges

Introduction: Production of functionalised particles using dry powder coating is a one-step, environmentally friendly process that paves the way for the development of particles with targeted properties and diverse functionalities. Areas covered: Applying the first principles in physical science for powders, fine guest particles can be homogeneously dispersed over the surface of larger host particles to develop functionalised particles. Multiple functionalities can be modified including: flowability, dispersibility, fluidisation, homogeneity, content uniformity and dissolution profile. The current publication seeks to understand the fundamental underpinning principles and science governing dry coating process, evaluate key technologies developed to produce functionalised particles along with outlining their advantages, limitations and applications and discusses in detail the resultant functionalities and their applications. Expert opinion: Dry particle coating is a promising solvent-free manufacturing technology to produce particles with targeted functionalities. Progress within this area requires the development of continuous processing devices that can overcome challenges encountered with current technologies such as heat generation and particle attrition. Growth within this field requires extensive research to further understand the impact of process design and material properties on resultant functionalities.

Design of experiments to study the impact of process parameters on droplet size and development of non-invasive imaging techniques in tablet coating

Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats.

Microparticle surface layering through dry coating:impact of moisture content and process parameters on the properties of orally disintegrating tablets

OBJECTIVES: The aim of this study was to investigate the influence of process parameters during dry coating on particle and dosage form properties upon varying the surface adsorbed moisture of microcrystalline cellulose (MCC), a model filler/binder for orally disintegrating tablets (ODTs). METHODS: The moisture content of MCC was optimised using the spray water method and analysed using thermogravimetric analysis. Microproperty/macroproperty assessment was investigated using atomic force microscopy, nano-indentation, scanning electron microscopy, tablet hardness and disintegration testing. KEY FINDINGS: The results showed that MCC demonstrated its best flowability at a moisture content of 11.2% w/w when compared to control, comprising of 3.9% w/w moisture. The use of the composite powder coating process (without air) resulted in up to 80% increase in tablet hardness, when compared to the control. The study also demonstrated that surface adsorbed moisture can be displaced upon addition of excipients during dry processing circumventing the need for particle drying before tabletting. CONCLUSIONS: It was concluded that MCC with a moisture content of 11% w/w provides a good balance between powder flowability and favourable ODT characteristics.