Importance of air bubbles in the core of coated pellets: Synchrotron X-ray microtomography allows for new insights

Fahier, Julie; Muschert, Susanne; Fayard, Barbara; Velghe, C.; Byrne, Gerard; Doucet, J.; Siepmann, Florence; Siepmann, Juergen

doi:10.1016/j.jconrel.2016.06.041

Cited by 12 publications

(6 citation statements)

References 36 publications

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“…Figure 5 b,c reveal that, in module variants with lids, cores with a normal fill volume created a headspace between the core and the lid. This headspace and core porosity are both sources of air within MV3, which could contribute to orifice obstruction or variable release kinetics [ 79 ]. Note that in final drug release tests involving MV3, this headspace was eliminated by overfilling of the PLA cup with the core.…”

Section: Resultsmentioning

confidence: 99%

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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Section: Resultsmentioning

confidence: 99%

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

et al. 2020

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“…Fahier et al utilized synchrotron radiation X-rays to discover possible transport mechanisms by which air bubbles control drug release in coated pellets. A drug release mechanism was proposed based on the structural behavior of propranolol pellets: the release of propranolol may be controlled by convection, mainly through the cracks in the coating layer …”

Section: Discovery Of 3d Structures In Ddssmentioning

confidence: 99%

“…A drug release mechanism was proposed based on the structural behavior of propranolol pellets: the release of propranolol may be controlled by convection, mainly through the cracks in the coating layer. 41 2. characteristics (Figure 5C). For example, the static structure of the RLD pellets was smooth, and there were no obvious gaps between the drug layer and the pellet core.…”

Section: Correlation Of Drug Release Kinetics With Pelletsmentioning

confidence: 99%

Advances in Structure Pharmaceutics from Discovery to Evaluation and Design

Xue

et al. 2023

Mol. Pharmaceutics

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Drug delivery systems (DDSs) play an important role in delivering active pharmaceutical ingredients (APIs) to targeted sites with a predesigned release pattern. The chemical and biological properties of APIs and excipients have been extensively studied for their contribution to DDS quality and effectiveness; however, the structural characteristics of DDSs have not been adequately explored. Structure pharmaceutics involves the study of the structure of DDSs, especially the three-dimensional (3D) structures, and its interaction with the physiological and pathological structure of organisms, possibly influencing their release kinetics and targeting abilities. A systematic overview of the structures of a variety of dosage forms, such as tablets, granules, pellets, microspheres, powders, and nanoparticles, is presented. Moreover, the influence of structures on the release and targeting capability of DDSs has also been discussed, especially the in vitro and in vivo release correlation and the structure-based organ- and tumor-targeting capabilities of particles with different structures. Additionally, an in-depth discussion is provided regarding the application of structural strategies in the DDSs design and evaluation. Furthermore, some of the most frequently used characterization techniques in structure pharmaceutics are briefly described along with their potential future applications.

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“…However, drug release mechanisms from pellets coated with polymeric films can be rather complex. A variety of processes might be involved in the controlled release of the drug out of the device such as water penetration into system [ 5 , 6 , 7 ], drug dissolution [ 8 , 9 ], drug diffusion through the intact film coating [ 10 , 11 ], crack formation in the film coating due to hydrostatic pressure built up in the core [ 12 , 13 ], dynamic changes in the local pH in the pellet core [ 14 ] and in the composition of the film coating [ 15 , 16 , 17 , 18 , 19 , 20 ] (e.g., resulting from the leaching of a water-soluble compound into the surrounding bulk fluid, limited drug solubility effects, to mention just a few). It is desirable to know which mass transport mechanisms play a role in the coated pellet formulation of interest: The knowledge on the underlying drug release mechanisms contributes to an improved device optimization during product development as well as quality control.…”

Section: Introductionmentioning

confidence: 99%

Towards a Better Understanding of Verapamil Release from Kollicoat SR:IR Coated Pellets Using Non-Invasive Analytical Tools

et al. 2021

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The aim of this study was to gain deeper insight into the mass transport mechanisms controlling drug release from polymer-coated pellets using non-invasive analytical tools. Pellet starter cores loaded with verapamil HCl (10% loading, 45% lactose, 45% microcrystalline cellulose) were prepared by extrusion/spheronization and coated with 5% Kollicoat SR:IR 95:5 or 10% Kollicoat SR:IR 90:10. Drug release was measured from ensembles of pellets as well as from single pellets upon exposure to acetate buffer pH = 3.5 and phosphate buffer pH = 7.4. The swelling of single pellets was observed by optical microscopy, while dynamic changes in the pH in the pellet cores were monitored by fluorescence spectroscopy. Also, mathematical modeling using a mechanistically realistic theory as well as SEM and Raman imaging were applied to elucidate whether drug release mainly occurs by diffusion through the intact film coatings or whether crack formation in the film coatings plays a role. Interestingly, fluorescence spectroscopy revealed that the pH within the pellet cores substantially differed upon exposure to acetate buffer pH = 3.5 and phosphate buffer pH = 7.4, resulting in significant differences in drug solubility (verapamil being a weak base) and faster drug release at lower pH: from ensembles of pellets and single pellets. The monitoring of drug release from and the swelling of single pellets indicated that crack formation in the film coatings likely plays a major role, irrespective of the Kollicoat SR:IR ratio/coating level. This was confirmed by mathematical modeling, SEM and Raman imaging. Importantly, the latter technique allowed also for non-invasive measurements, reducing the risk of artifact creation associated with sample cutting with a scalpel.

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Importance of air bubbles in the core of coated pellets: Synchrotron X-ray microtomography allows for new insights

Cited by 12 publications

References 36 publications

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

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

Advances in Structure Pharmaceutics from Discovery to Evaluation and Design

Towards a Better Understanding of Verapamil Release from Kollicoat SR:IR Coated Pellets Using Non-Invasive Analytical Tools

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