Melt extrusion vs. spray drying: The effect of processing methods on crystalline content of naproxen-povidone formulations

Haser, Abbe; Cao, Tu; Lubach, Joe; Listro, Tony; Acquarulo, Larry; Zhang, Feng

doi:10.1016/j.ejps.2017.02.038

Cited by 32 publications

(33 citation statements)

References 36 publications

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“…[10][11][12] A complementary set of techniques would commonly be used to characterize a formulation, but have their own limitations which stem from properties of the instrument or sample. Polarized light microscopy (PLM) may be highly sensitive for detection of crystalline content, even when XRPD has determined a sample to be amorphous, 13 but this technique is limited by spatial resolution caused by the diffraction limitation. Differential scanning calorimetry (DSC) is limited by mass fraction, domain size, and the dynamic heating process.…”

Section: Introductionmentioning

confidence: 99%

Nanometer-Scale Residual Crystals in a Hot Melt Extruded Amorphous Solid Dispersion: Characterization by Transmission Electron Microscopy

Moseson

Mugheirbi

Stewart

et al. 2018

Crystal Growth & Design

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Common characterization techniques used to detect crystallinity in amorphous solid dispersions (ASD) typically have detection or quantification limits on the order of 1%. Herein, an amorphous solid dispersion of indomethacin and polyvinylpyrrolidone/vinyl acetate copolymer (PVPVA) produced by hot melt extrusion was determined to be amorphous by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). However, through the use of transmission electron microscopy (TEM), residual crystals of two populations were identified: single crystals mid-dissolution (<100 nm) and nanocrystalline domains of 5-10 nm in size. Both domain types were observed to contain a high defect density. Polarized light microscopy (PLM) and scanning electron microscopy (SEM) techniques supplement these findings by corroborating crystallinity. The use of high resolution analytical techniques to identify and characterize residual crystallinity is considered an important first step to understanding the significance of these residual crystalline populations to ASD performance attributes.

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Section: Introductionmentioning

confidence: 99%

Nanometer-Scale Residual Crystals in a Hot Melt Extruded Amorphous Solid Dispersion: Characterization by Transmission Electron Microscopy

Moseson

Mugheirbi

Stewart

et al. 2018

Crystal Growth & Design

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“…Because the inherent miscibility of SDSD is a direct consequence of droplets drying kinetically during the spray-drying process, this finding confirms the ability of our novel miniaturized equipment to reproduce the microscale evaporation mechanism that occurs across a larger dryer. During droplet solvent evaporation, a drug may have the opportunity to recrystallize during a small interval of time when drug solubility reaches saturation in a solvent and when polymer viscosity is not enough to stabilize the amorphous form of the drug [8]. Therefore, this qualifies the design and operating mode of our miniaturized system compared to laboratory equipment.…”

Section: Miscibility and Solid State Properties Of Sdsdsmentioning

confidence: 99%

“…The use of spray-drying has been particularly suitable for the preparation of amorphous solid dispersions (ASDs) at the industrial scale [7]. This can be explained on the basis that the rapid solvent evaporation that occurs during the process minimizes the time window for phase separation and recrystallization and favors the formation of an amorphous system [8]. Manufacturing of stable ASDs is currently one of the most investigated formulation strategies in drug delivery design to overcome solubility challenges of class II and class IV drugs (according to the biopharmaceutics classification system) [9].…”

Section: Introductionmentioning

confidence: 99%

Comparison of a Novel Miniaturized Screening Device with Büchi B290 Mini Spray-Dryer for the Development of Spray-Dried Solid Dispersions (SDSDs)

et al. 2018

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Spray-drying is an increasingly popular technology for the production of amorphous solid dispersions (ASDs) in the pharmaceutical industry that is used in the early evaluation and industrial production of formulations. Efficient screening of ASD in the earliest phase of drug development is therefore critical. A novel miniaturized atomization equipment for screening spray-dried solid dispersions (SDSDs) in early formulation and process development was developed. An in-depth comparison between the equipment/process parameters and performance of our novel screening device and a laboratory Büchi B290 mini spray-dryer was performed. Equipment qualification was conducted by comparing the particle/powder attributes, i.e., miscibility/solid state, residual solvent, and morphological properties of binary SDSDs of itraconazole prepared at both screening and laboratory scales. The operating mode of the miniaturized device was able to reproduce similar process conditions/parameters (e.g., outlet temperature (Tout)) and to provide particles with similar drug–polymer miscibility and morphology as laboratory-scale SDSDs. These findings confirm that the design and operation of this novel screening equipment mimic the microscale evaporation mechanism of a larger spray-dryer. The miniaturized spray-dryer was therefore able to provide a rational prediction of adequate polymer and drug loading (DL) for SDSD development while reducing active pharmaceutical ingredient (API) consumption by a factor of 120 and cycle time by a factor of 4.

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“…In another such study, HPLC-PDA was used to determine the chemical degradation of naproxen mixed with PVP K25 after HME (co-rotating twin-screw extruder, barrel temperature 90 or 120 °C, screw speed 150 rpm) or spray drying (inlet temperature 100 °C, outlet temperature 60 °C). Minimal degradation (0.80 ± 0.01%) was observed subsequent to HME, while none at all was observed in association with the spray drying process [ 61 ].…”

Section: Introductionmentioning

confidence: 99%

“…XRPD was also exploited to assess crystallinity quantitation in a mix of naproxen-povidone treated under HME, in this case through the Ruland’s method, with the T g calculated by MTDSC. Haser et al [ 61 ] formulated naproxen in presence of povidone K25 at different percentages under HME or spray drying. By XRPD, the authors proved that spray dried mixes were more susceptible to re-crystallization.…”

Section: Introductionmentioning

confidence: 99%

Hot Melt Extrusion: Highlighting Physicochemical Factors to Be Investigated While Designing and Optimizing a Hot Melt Extrusion Process

et al. 2018

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Hot-melt extrusion (HME) is a well-accepted and extensively studied method for preparing numerous types of drug delivery systems and dosage forms. It offers several advantages: no solvents are required, it is easy to scale up and employ on the industrial level, and, in particular, it offers the possibility of improving drug bioavailability. HME involves the mixing of a drug with one or more excipients, in general polymers and even plasticizers, which can melt, often forming a solid dispersion of the drug in the polymer. The molten mass is extruded and cooled, giving rise to a solid material with designed properties. This process, which can be realized using different kinds of special equipment, may involve modifications in the drug physicochemical properties, such as chemical, thermal and mechanical characteristics thus affecting the drug physicochemical stability and bioavailability. During process optimization, the evaluation of the drug solid state and stability is thus of paramount importance to guarantee stable drug properties for the duration of the drug product shelf life. This manuscript reviews the most important physicochemical factors that should be investigated while designing and optimizing a hot melt extrusion process, and by extension, during the different pre-formulation, formulation and process, and post-formulation phases. It offers a comprehensive evaluation of the chemical and thermal stability of extrudates, the solid physical state of extrudates, possible drug-polymer interactions, the miscibility/solubility of the drug-polymer system, the rheological properties of extrudates, the physicomechanical properties of films produced by hot melt extrusion, and drug particle dissolution from extrudates. It draws upon the last ten years of research, extending inquiry as broadly as possible.

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Melt extrusion vs. spray drying: The effect of processing methods on crystalline content of naproxen-povidone formulations

Cited by 32 publications

References 36 publications

Nanometer-Scale Residual Crystals in a Hot Melt Extruded Amorphous Solid Dispersion: Characterization by Transmission Electron Microscopy

Nanometer-Scale Residual Crystals in a Hot Melt Extruded Amorphous Solid Dispersion: Characterization by Transmission Electron Microscopy

Comparison of a Novel Miniaturized Screening Device with Büchi B290 Mini Spray-Dryer for the Development of Spray-Dried Solid Dispersions (SDSDs)

Hot Melt Extrusion: Highlighting Physicochemical Factors to Be Investigated While Designing and Optimizing a Hot Melt Extrusion Process

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