A predictive integrated framework based on the radial basis function for the modelling of the flow of pharmaceutical powders

This study presents a modelling framework to predict the flowability of various commonly used pharmaceutical powders and their blends. The flowability models were trained and validated on 86 samples including single components and binary mixtures. Two modelling paradigms based on artificial intelligence (AI) namely, a radial basis function (RBF) and an integrated network were employed to model the flowability represented by the flow function coefficient (FFC) and the bulk density (RHOB). Both approaches were utilized to map the input parameters (i.e. particle size, shape descriptors and material type) to the flow properties. The input parameters of the blends were determined from the particle size, shape and material type properties of the single components. The results clearly indicated that the integrated network outperformed the single RBF network in terms of the predictive performance and the generalization capabilities. For the integrated network, the coefficient of determination of the testing data set (not used for training the model) for FFC was R2=0.93, reflecting an acceptable predictive power of this model. Since the flowability of the blends can be predicted from single component size and shape descriptors, the integrated network can assist formulators in selecting excipients and their blend concentrations to improve flowability with minimal experimental effort and material resulting in the (i) minimization of the time required, (ii) exploration and examination of the design space, and (iii) minimization of material waste

Hot-melt extrusion process impact on polymer choice of glyburide solid dispersions : the effect of wettability and dissolution

The aim of this study was to evaluate the choice of polymer and polymer level on the performance of the microstructure and wettability of hot-melt extruded solid dispersion of Glyburide (Gly) as a model drug. The produced solid dispersion were characterised using scanning electron microscopy (SEM), image analysis using a focus variation instrument (FVI), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), X-ray microtomography (XµT), dynamic contact angle measurement and dissolution analysis using biorelevant dissolution media (FASSIF). SEM and focus variation analysis showed that the microstructure and surface morphology was significantly different between samples produced. This was confirmed by further analysis using XµT which showed that an increase in polymer content brought about a decrease in the porosity of the hot-melt extruded dispersions. DSC suggested complete amorphorisation of Gly whereas XRPD suggested incomplete amorphorisation. The static and dynamic contact angle measurement correlated with the dissolution studies using FASSIF media indicating that the initial liquid imbibition process as captured by the dynamic contact angle directly affects the dissolution performance

An investigation into the effect of particle and formulation properties on the performance of pharmaceutical powders using novel experimental and modelling techniques

This thesis provides a piece of comprehensive information on the interrelationship between particle properties, formulation properties, and the performance of pharmaceutical powders. Three main performance categories were investigated; these include flow, disintegration, and dissolution. The effect of formulation properties on the dissolution performance of a pharmaceutical formulation containing a low soluble active pharmaceutical ingredient was explored. A novel, dynamic contact angle measurement technique was used to understand wetting behaviour and provide correlations with dissolution testing using biorelevant dissolution media. In addition, this thesis explored the link between the microstructure obtained by X-ray microtomography and the dissolution performance. The thesis also investigates how formulation properties such as disintegrant type and the amount of lubricant affects the disintegration behaviour of pharmaceutical tablets by coupling a novel surface imaging instrument with an in-line particle size analyser. This thesis also presents novel data analysis techniques with the aim to build a modelling framework that can be used to relate particle properties of pharmaceutical powders such as particle size and shape to their flow performance. Radial basis function (RBF) and neural network techniques were used to achieve this goal. Traditional data analysis techniques such as multivariate data analysis were used to build correlations between particle properties and powder performance. This is of great importance in the early stages of drug discovery activities. The information from this thesis therefore demonstrates how novel experimental and modelling techniques can be used to related particle properties and formulation properties to the performance of pharmaceutical powders

Comparative Evaluation of the Powder and Tableting Properties of Regular and Direct Compression Hypromellose from Different Vendors

Hypromellose, a widely used polymer in the pharmaceutical industry, is available in several grades, depending on the percentage of substitution of the methoxyl and hydroxypropyl groups and molecular weight, and in various functional forms (e.g., suitable for direct compression tableting). These differences can affect their physicomechanical properties, and so this study aims to characterise the particle size and mechanical properties of HPMC K100M polymer grades from four different vendors. Eight polymers (CR and DC grades) were analysed using scanning electron microscopy (SEM) and light microscopy automated image analysis particle characterisation to examine the powder’s particle morphology and particle size distribution. Bulk density, tapped density, and true density of the materials were also analysed. Flow was determined using a shear cell tester. Flat-faced polymer compacts were made at five different compression forces and the mechanical properties of the compacts were evaluated to give an indication of the powder’s capacity to form a tablet with desirable strength under specific pressures. The results indicated that the CR grades of the polymers displayed a smaller particle size and better mechanical properties compared to the DC grade HPMC K100M polymers. The DC grades, however, had better flow properties than their CR counterparts. The results also suggested some similarities and differences between some of the polymers from the different vendors despite the similarity in substitution level, reminding the user that care and consideration should be given when substitution is required