A Miniaturized Extruder to Prototype Amorphous Solid Dispersions: Selection of Plasticizers for Hot Melt Extrusion

Lauer, Matthias E.; Maurer, Reto; Paepe, Anne T. De; Stillhart, Cordula; Jacob, Laurence; James, R. N.; Kojima, Yuki; Rietmann, Rene; Kissling, Tom; Ende, Joost A. van den; Schwarz, Sabine; Grassmann, Olaf; Page, Susanne

doi:10.3390/pharmaceutics10020058

Cited by 12 publications

(11 citation statements)

References 46 publications

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“…In comparison, when drug loading was increased to 0.65 w/w (predicted to be crystalline in NPX-EPO system), a sudden increase on surface roughness with the appearance of structured particles can be observed by the AFM (Figure 11 c, f and g). With the calculated root mean square surface roughness for each extruded systems, it was possible to direct visualise the transitions of the system from onephase amorphous to extrudates with residual crystals (Lauer et al, 2018).…”

Section: Verification Of Residual Crystal In Extrudatesmentioning

confidence: 99%

The design and development of high drug loading amorphous solid dispersion for hot-melt extrusion platform

Tian

Jacobs

McCoy

et al. 2020

International Journal of Pharmaceutics

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Amorphous solid dispersion (ASD) is a formulation strategy extensively used to enhance the bioavailability of poorly water soluble drugs. Despite this, they are limited by various factors such as limited drug loading, poor stability, drugexcipient miscibility and the choice of process platforms. In this work, we have developed a strategy for the manufacture of high drug loaded ASD (HDASD) using hot-melt extrusion (HME) based platform. Three drug-polymer combinations, indomethacin-Eudragit®E, naproxen-Eudragit®E and ibuprofen-Eudragit®E, were used as the model systems. The design spaces were predicted through Flory-Huggins based theory, and the selected HDASDs at pre-defined conditions were manufactured using HME and quench-cooled melt methods. These HDASD systems were also extensively characterised via small angle/wide angle x-ray scattering, differential scanning calorimetry, Infrared and Raman spectroscopy and atomic force microscopy. It was verified that HDASDs were successfully produced via HME platform at the pre-defined conditions, with maximum drug loadings of 0.65, 0.70 and 0.60 w/w for drug indomethacin, ibuprofen and naproxen respectively. Enhanced physical stability was further confirmed by high humidity (95%RH) storage stability studies. Through this work, we have demonstrated that by the implementation of predictive thermodynamic modelling, HDASD formulation design can be integrated into the HME process design to ensure the desired quality of the final dosage form.

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Section: Verification Of Residual Crystal In Extrudatesmentioning

confidence: 99%

The design and development of high drug loading amorphous solid dispersion for hot-melt extrusion platform

Tian

Jacobs

McCoy

et al. 2020

International Journal of Pharmaceutics

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“…However, for a fusion-based product via HME, its results might deviate. A recent publication combines solvent casting with a simplified extrusion step to become a fusion-based screening method [21]. Novel approaches are also combining rapid solvent evaporation methods with an additional heating step, which is quite successful in estimating formulation performance [22].…”

Section: Solvent Castingmentioning

confidence: 99%

Vacuum Compression Molding as a Screening Tool to Investigate Carrier Suitability for Hot-Melt Extrusion Formulations

et al. 2020

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Hot-melt extrusion (HME) is the most preferred and effective method for manufacturing amorphous solid dispersions at production scale, but it consumes large amounts of samples when used for formulation development. Herein, we show a novel approach to screen the polymers by overcoming the disadvantage of conventional HME screening by using a minimum quantity of active pharmaceutical ingredient (API). Vacuum Compression Molding (VCM) is a fusion-based method to form solid specimens starting from powders. This study aimed to investigate the processability of VCM for the creation of amorphous formulations and to compare its results with HME-processed formulations. Mixtures of indomethacin (IND) with drug carriers (Parteck® MXP, Soluplus®, Kollidon® VA 64, Eudragit® EPO) were processed using VCM and extrusion technology. Thermal characterization was performed using differential scanning calorimetry, and the solid-state was analyzed via X-ray powder diffraction. Dissolution studies in the simulated gastric fluid were performed to evaluate the drug release. Both technologies showed similar results proving the effectiveness of VCM as a screening tool for HME-based formulations.

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“…Many drugs are insoluble or poorly water soluble, and improving their dissolution is one of the central challenges in pharmaceutics [ 1 , 2 , 3 , 4 ]. Among the different kinds of strategies that have been broadly investigated to resolve this problem, drug solid dispersions (SDs) are some of the most promising ways with many commercial products [ 5 , 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Fast Dissolving of Ferulic Acid via Electrospun Ternary Amorphous Composites Produced by a Coaxial Process

et al. 2018

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Enhancing the dissolution of insoluble active ingredients comprises one of the most important issues in the pharmaceutical and biomaterial fields. Here, a third generation solid dispersion (3rd SD) of ferulic acid was designed and fabricated by a modified coaxial electrospinning process. A traditional second generation SD (2nd SD) was also prepared by common one-fluid blending electrospinning and was used as a control. With poly(vinyl alcohol) as the fiber matrix and polyvinylpyrrolidone K10 as an additive in the 3rd SDs, the two electrospinning processes were investigated. The prepared 2nd and 3rd SDs were subjected to a series of characterizations, including X-ray diffraction (XRD), scanning electron microscope (SEM), hydrophilicity and in vitro drug dissolving experiments. The results demonstrate that both SDs were monolithic nanocomposites and that the drugs were amorphously distributed within the matrix. However, the 3rd SDs had better morphology with smaller size, narrower size distribution, and smaller water contact angles than the 2nd SDs. Dissolution tests verified that the 3rd SDs could release their loaded cargoes within 60 s, which was over three times faster than the 2nd SDs. Therefore, a combined strategy based on the modified coaxial electrospinning and the logical selections of drug carriers is demonstrated for creating advanced biomaterials.

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A Miniaturized Extruder to Prototype Amorphous Solid Dispersions: Selection of Plasticizers for Hot Melt Extrusion

Cited by 12 publications

References 46 publications

The design and development of high drug loading amorphous solid dispersion for hot-melt extrusion platform

The design and development of high drug loading amorphous solid dispersion for hot-melt extrusion platform

Vacuum Compression Molding as a Screening Tool to Investigate Carrier Suitability for Hot-Melt Extrusion Formulations

Fast Dissolving of Ferulic Acid via Electrospun Ternary Amorphous Composites Produced by a Coaxial Process

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