High Content Solid Dispersions for Dose Window Extension: A Basis for Design Flexibility in Fused Deposition Modelling

Govender, Rydvikha; Abrahmsén-Alami, Susanna; Folestad, Staffan; Larsson, Anette

doi:10.1007/s11095-019-2720-6

Cited by 17 publications

(18 citation statements)

References 37 publications

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“…3D-printed systems containing poorly soluble drugs have been examined; however, the stability of these formulations has not been evaluated thoroughly. In a recent study, Govender et al examined this issue, showing good stability with high percentages of drug incorporation, albeit with a polymer insoluble in water [43]. It has also been demonstrated that amorphization via hot-melt extrusion and subsequent FDM can produce formulations in which the drug quickly recrystallizes [44].…”

Section: Introductionmentioning

confidence: 99%

3D-Printed Mesoporous Carrier System for Delivery of Poorly Soluble Drugs

et al. 2021

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Fused deposition modelling (FDM) is the most extensively employed 3D-printing technique used in pharmaceutical applications, and offers fast and facile formulation development of personalized dosage forms. In the present study, mesoporous materials were incorporated into a thermoplastic filament produced via hot-melt extrusion and used to produce oral dosage forms via FDM. Mesoporous materials are known to be highly effective for the amorphization and stabilization of poorly soluble drugs, and were therefore studied in order to determine their ability to enhance the drug-release properties in 3D-printed tablets. Celecoxib was selected as the model poorly soluble drug, and was loaded into mesoporous silica (MCM-41) or mesoporous magnesium carbonate. In vitro drug release tests showed that the printed tablets produced up to 3.6 and 1.5 times higher drug concentrations, and up to 4.4 and 1.9 times higher release percentages, compared to the crystalline drug or the corresponding plain drug-loaded mesoporous materials, respectively. This novel approach utilizing drug-loaded mesoporous materials in a printed tablet via FDM shows great promise in achieving personalized oral dosage forms for poorly soluble drugs.

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Section: Introductionmentioning

confidence: 99%

3D-Printed Mesoporous Carrier System for Delivery of Poorly Soluble Drugs

et al. 2021

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“…However, the final target orifice diameter for the MV3 constructs used in subsequent drug release testing was 0.8 mm. Previous studies have shown that FDM dispensing precision decreases with dispensing volume [ 70 ]. It can therefore be concluded that larger feature sizes are expected to be generated with higher precision during FDM.…”

Section: Resultsmentioning

confidence: 99%

“…Identical doses within individual module variants, if desired, could have been achieved through overfilling of MV1 and MV2 cores to match overfilling of MV3 cores. Alternatively, achieving scalable individualized dosing with modular dosage form design concepts at a fixed dosage form size was already addressed in our previous work [ 70 ]. As described above, maintaining acceptable dosage form sizes independent of the dose strength requires modules that are a fraction of the size of a conventional dosage form.…”

Section: Discussionmentioning

confidence: 99%

“…However, it has been exemplified, through a modular product design concept for improving dose flexibility, that a large number of module variants are not necessary to yield high product variety, with only five module dose variants capable of providing 100 product dose variants [ 68 ]. Consequently, the proposed modular product concept can achieve simultaneous and independent tailoring of dose and drug release through spatial separation of the entire dose from the release-controlling functionalities allowing predictable modular dosing through modularization of the core [ 70 ] and predictable modular drug release.…”

Section: Discussionmentioning

confidence: 99%

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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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“…For these modular product designs, cost and benefit studies were conducted. Govender et al [9] and Govender et al [10] experimentally showed the realization of a modular product design for a pharmaceutical product with a scalable dose strength and flexible, but controlled, target release profile. Building on the studies by Siiskonen et al [8], Govender et al [9], and Govender et al [10], the novelty of this paper is a theoretical modeling approach to generate modular product designs for pharmaceutical products for cost-efficient customization.…”

Section: Introductionmentioning

confidence: 99%

Pharmaceutical Product Modularization as a Mass Customization Strategy to Increase Patient Benefit Cost-Efficiently

Siiskonen

Malmqvist

Folestad

2021

Systems

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Customized pharmaceutical products aim to comply with the individual needs of a patient to enhance the treatment outcome. The current pharmaceutical production paradigm is, however, dominated by mass production, where the pharmaceutical products embrace a one-size-fits-all design with a low possibility of treatment optimization to patient needs. This production paradigm is not designed or intended for customized pharmaceutical products and operating this production context for customized pharmaceutical products is argued to be cost-inefficient. To address this challenge of inefficient production of customized pharmaceutical products, this study proposes an approach to modular pharmaceutical product design. As a mass customization strategy, product modularization enables serving customers with customized products cost-efficiently. The proposed modular pharmaceutical products integrate three product design requirements originating from patient needs: a scalable dose strength, a flexible target release profile, and a scalable treatment size. An approach to assess the value of these product designs is presented, by means of proposing three benefit metrics complying with respective design requirements and a cost metric assessing the cost of producing these modular pharmaceutical product designs. Results suggest that pharmaceutical product modularization can, by keeping the number of produced components low, substantially increase the external product variety and, hence, enhance the treatment outcome of patients. Furthermore, results indicate that the achieved benefit for the patient through product modularization increases beyond additional costs arising during production. However, a careful modularization must be performed to optimize the tradeoff between the increased benefit and cost.

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High Content Solid Dispersions for Dose Window Extension: A Basis for Design Flexibility in Fused Deposition Modelling

Cited by 17 publications

References 37 publications

3D-Printed Mesoporous Carrier System for Delivery of Poorly Soluble Drugs

3D-Printed Mesoporous Carrier System for Delivery of Poorly Soluble Drugs

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

Pharmaceutical Product Modularization as a Mass Customization Strategy to Increase Patient Benefit Cost-Efficiently

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