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

Alshafiee, Maen; Aljammal, Mohammad Khaled; Markl, Daniel; Ward, Adam; Walton, Karl; Blunt, Liam; Korde, Sachin; Pagire, Sudhir K.; Kelly, Adrian L.; Paradkar, Anant; Conway, Barbara R.; Asare-Addo, Kofi

doi:10.1016/j.ijpharm.2019.01.038

Cited by 30 publications

(6 citation statements)

References 45 publications

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“…Since both polymer type and drug loading may affect viscosity of the molten mixture in the extruder, both may affect cavity formation by changing viscosity. This result agrees well with the similar void-forming phenomena reported in the literature (Alshafiee et al, 2019, Martinez-Marcos et al, 2016, Fukuda et al, 2006. In addition to the differences observed in the numbers of voids in the extrudates with different drug loadings, the diameters of the extrudates also increases with increasing the drug content and the screw speed, as shown in Figure 7.…”

Section: Effect Of Viscositysupporting

confidence: 92%

“…However, recently a number of studies reported the use of additives, such as disintegrants and other particulate excipients that form a separate phase to the drug dispersion (Fukuda et al, 2006, Alqahtani et al, 2020, Deng et al, 2013, Krupa et al, 2017, Sadia et al, 2018, Sadia et al, 2016, Crowley et al, 2004. Occasionally, voids were observed in extrudates (Alqahtani et al, 2020, Alshafiee et al, 2019, Fukuda et al, 2006, Martinez-Marcos et al, 2016, Almeida et al, 2011, Crowley et al, 2004. We specifically term such structural features as voids rather than pores because they typically are isolated pockets in the interior of the extrudates and they are not, in most cases, apparent on the surface of the extrudates.…”

Section: Introductionmentioning

confidence: 99%

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An investigation into the formations of the internal microstructures of solid dispersions prepared by hot melt extrusion

Alqahtani

Belton

Zhang

et al. 2020

European Journal of Pharmaceutics and Biopharmaceutics

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Hot melt extrusion (HME) is a widely used manufacturing process for pharmaceutical solid dispersions. The complexity of the HME formulations and the number of excipients used in the process are increasing with the advancement of the relevant knowledge. However, one of the areas that are still significantly lacking understanding is the control of internal microstructure of extrudates. Internal microstructure, consisting of voids, in hot melt extruded amorphous solid dispersions is often observed without the causes having been systemically investigated in the literature. In this study, we investigated a range of factors that demonstrated their impacts on the formation of the voids. These include the effect of the types of the materials (i.e. drug, polymer and additive) used in the formulation, the quantity of the drug and the additives used, the key extrusion processing parameters, the type of extruder, and the drying of the raw materials prior to extrusion. The results indicate that the appropriate viscosity and the presence of phase-separated particulates are essential for the formation of the voids. The particulates act as nuclei for the entrapped gas bubbles and the viscosity of the mixture during extrusion governs the collapse/escape of the bubbles. To minimise void formation, the results of this study indicate that slow screw speed, low moisture content of the raw materials, fewer particulates and the addition of lubricants, such as low melting lipid excipients, could be beneficial. This study systematically examines the mechanism of void formation in HME extrudates and generates new strategies that can be used to manage such void formations.

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Section: Effect Of Viscositysupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

An investigation into the formations of the internal microstructures of solid dispersions prepared by hot melt extrusion

Alqahtani

Belton

Zhang

et al. 2020

European Journal of Pharmaceutics and Biopharmaceutics

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“…Figure 5 also shows that porosity was present in all cores after melt molding. Porosity has been observed previously in melt-extruded VA64 filaments [ 78 ]. However, unlike the applied force exerted by the screws during mixing in melt extrusion, we postulate that the melt molding process, which involved loose stacking of filament sections in the cup followed by melting without any applied force, was likely to contribute more to eventual core porosity.…”

Section: Resultsmentioning

confidence: 57%

Independent Tailoring of Dose and Drug Release via a Modularized Product Design Concept for Mass Customization

et al. 2020

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Independent individualization of multiple product attributes, such as dose and drug release, is a crucial overarching requirement of pharmaceutical products for individualized therapy as is the unified integration of individualized product design with the processes and production that drive patient access to such therapy. Individualization intrinsically demands a marked increase in the number of product variants to suit smaller, more stratified patient populations. One established design strategy to provide enhanced product variety is product modularization. Despite existing customized and/or modular product design concepts, multifunctional individualization in an integrated manner is still strikingly absent in pharma. Consequently, this study aims to demonstrate multifunctional individualization through a modular product design capable of providing an increased variety of release profiles independent of dose and dosage form size. To further exhibit that increased product variety is attainable even with a low degree of product modularity, the modular design was based upon a fixed target dosage form size of approximately 200 mm3 comprising two modules, approximately 100 mm3 each. Each module contained a melt-extruded and molded formulation of 40% w/w metoprolol succinate in a PEG1500 and Kollidon® VA64 erodible hydrophilic matrix surrounded by polylactic acid and/or polyvinyl acetate as additional release rate-controlling polymers. Drug release testing confirmed the generation of predictable, combined drug release kinetics for dosage forms, independent of dose, based on a product’s constituent modules and enhanced product variety through a minimum of six dosage form release profiles from only three module variants. Based on these initial results, the potential of the reconfigurable modular product design concept is discussed for unified integration into a pharmaceutical mass customization/mass personalization context.

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“…Kolliphor ® P 407 is a triblock polymer composed of a central block of hydrophobic polypropylene oxide (PPO) surrounded by two hydrophilic blocks of polyethyleneoxide (PEO). The molecular weight of this polymer is in the range of 9840-14600 daltons [14,15]. It shows the phenomena of micellization due to its amphiphilic nature [16].…”

Section: Introductionmentioning

confidence: 97%

How to Improve Solubility and Dissolution of Irbesartan by Fabricating Ternary Solid Dispersions: Optimization and In-Vitro Characterization

et al. 2022

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The purpose of this study is to improve the solubility and dissolution of a poorly soluble drug, Irbesartan, using solid dispersion techniques. For that purpose, different polymers such as Soluplus®, Kollidon®VA 64, Kolliphor®P 407, and Polyinylpyrrolidone (PVP-K30) were used as carriers at different concentrations to prepare solid dispersion formulations through the solvent evaporation method. In order to prepare binary dispersion formulations, Soluplus® and Kollidon®VA 64 were used at drug:polymer ratios of 1:1, 1:2, 1:3, and 1:4 (w/w). Saturation solubility of the drug in the presence of used carriers was performed to investigate the quantitative increase in solubility. Dissolution studies were performed to explore the drug release behavior from the prepared dispersions. Additionally, the characterization of the prepared formulations was carried out by performing DSC, SEM, XRD, and FTIR studies. The results revealed that among binary systems, K4 formulation (Drug:Kollidon®VA 64 at ratio of 1:4 w/w) exhibited optimal performance in terms of increased solubility, drug release, and other investigated parameters. Furthermore, ternary dispersion formulations of the optimized binary formulation were prepared with two more polymers, Kolliphor®P 407 and Polyvinylpyrrolidone (PVP-K30), at (Drug:Kollidon®VA 64:ternary polymer) ratios of 1:4:1, 1:4:2, and 1:4:3 (w/w). The results showed that KPVP (TD3) exhibited the highest increase in solubility, as well as dissolution rate, among ternary solid dispersion formulations. Results of solubility enhancement by ternary solid dispersion formulations were also supported by FTIR, DSC, XRD, and SEM analysis. Conclusively, it was found that the ternary solid dispersion-based systems were more effective compared to the binary combinations in improving solubility as well as dissolution of a poorly soluble drug (Irbesartan).

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

Cited by 30 publications

References 45 publications

An investigation into the formations of the internal microstructures of solid dispersions prepared by hot melt extrusion

An investigation into the formations of the internal microstructures of solid dispersions prepared by hot melt extrusion

Independent Tailoring of Dose and Drug Release via a Modularized Product Design Concept for Mass Customization

How to Improve Solubility and Dissolution of Irbesartan by Fabricating Ternary Solid Dispersions: Optimization and In-Vitro Characterization

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