Electron microscopy/energy dispersive X-ray spectroscopy of drug distribution in solid dispersions and interpretation by multifractal geometry

Abreu-Villela, Renata; Adler, Camille; Caraballo, Isidoro; Kuentz, Martin

doi:10.1016/j.jpba.2017.12.020

Cited by 8 publications

(5 citation statements)

References 29 publications

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“…Usually, the following two techniques are applied to generate sufficient heat: i) convective heating, i.e. , a microwave absorbing reactor or a sample holder is heated and this heat is then indirectly transferred to the sample 353 , 360 , 361 , 362 , 363 , 364 , 365 , 366 , 367 , 368 , 369 , 370 ; and ii) The addition of microwave absorbing solvent 371 or solvent slurry 372 , 373 to the drug-polymer solution mix and followed by solvent evaporation due to heating. For example, Moneghini et al.…”

Section: Manufacturing Methods For Preparing Amorphous Solid Dispersionsmentioning

confidence: 99%

“… 353 placed the physical mixture of ibuprofen and PVP-VA in a glass sample holder, and materials were heated due to the convective heating from glass, whereas Abreu-Villela et al. 372 manufactured ASDs by microwaving suspensions prepared by adding defined amounts of water to the drug-polymer physical mixture.…”

Section: Manufacturing Methods For Preparing Amorphous Solid Dispersionsmentioning

confidence: 99%

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Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Bhujbal

Mitra

Jain

et al. 2021

Acta Pharmaceutica Sinica B

276

131

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Amorphous solid dispersions (ASDs) are popular for enhancing the solubility and bioavailability of poorly water-soluble drugs. Various approaches have been employed to produce ASDs and novel techniques are emerging. This review provides an updated overview of manufacturing techniques for preparing ASDs. As physical stability is a critical quality attribute for ASD, the impact of formulation, equipment, and process variables, together with the downstream processing on physical stability of ASDs have been discussed. Selection strategies are proposed to identify suitable manufacturing methods, which may aid in the development of ASDs with satisfactory physical stability.

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Section: Manufacturing Methods For Preparing Amorphous Solid Dispersionsmentioning

confidence: 99%

Section: Manufacturing Methods For Preparing Amorphous Solid Dispersionsmentioning

confidence: 99%

Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Bhujbal

Mitra

Jain

et al. 2021

Acta Pharmaceutica Sinica B

276

131

View full text Add to dashboard Cite

show abstract

“…The fractal approach, based on the self-similarity concept, enables an understanding of the morphological characteristics of the filaments, and helps us to understand their behaviour in the extrusion process. Our research group is pioneering in the use of the fractal dimension [41][42][43], as well as in their application on 3D printing filaments [14]. In the present work, the fractal dimension was applied for the first time to study the roughness of hydrophilic filaments.…”

Section: Physical Appearance Of the Filamentsmentioning

confidence: 95%

Assessment of the Extrusion Process and Printability of Suspension-Type Drug-Loaded AffinisolTM Filaments for 3D Printing

et al. 2022

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Three-dimensional (3D) printing technology enables the design of new drug delivery systems for personalised medicine. Polymers that can be molten are needed to obtain extruded filaments for Fused Deposition Modelling (FDM), one of the most frequently employed techniques for 3D printing. The aim of this work was to evaluate the extrusion process and the physical appearance of filaments made of a hydrophilic polymer and a non-molten model drug. Metformin was used as model drug and Affinisol™ 15LV as the main carrier. Drug-loaded filaments were obtained by using a single-screw extruder and, subsequently, their printability was tested. Blends containing up to a 60% and 50% drug load with 5% and 7.5% of auxiliary excipients, respectively, were successfully extruded. Between the obtained filaments, those containing up to 50% of the drug were suitable for use in FDM 3D printing. The studied parameters, including residence time, flow speed, brittleness, and fractal dimension, reflect a critical point in the extrusion process at between 30–40% drug load. This finding could be essential for understanding the behaviour of filaments containing a non-molten component.

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“…Microwave heating has also been applied to process drug-polymer solutions and slurries using high-loss polar solvents for the fabrication of bulk ASD powders. For example, water has been used in API-hypromellose acetate succinate (HPMCAS) and API-HPMCAS-urea physical mixtures to prepare homogeneous slurries, which heated up and evaporated during microwaving to induce full amorphization of the API [77,78]. In another study, Radacsi et al prepared a niflumic acid-PVP-ethanol solution, which was subjected to a well-designed microwave-assisted evaporation setup with a constant power of 300 W [76], and a completely amorphous ASD was formed, showing a significantly enhanced dissolution performance relative to crystalline niflumic acid.…”

Section: Microwave Heating For Bulk Preparation Of Amorphous Glass Somentioning

confidence: 99%

“…However, unlike water, polymers and drug molecules are poor microwave absorbers [ 64 , 65 ] and hence do not heat up sufficiently on their own in order to form an ASD. As a consequence the preparative methods described in the literature typically take advantage of the following effects: i) convective heating, i.e., a microwave absorbing reactor or sample holder is heated up and this heat is then transferred to the sample indirectly [ 43 , 44 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ], and ii) addition of a microwave absorbing solvent to the formulation in excess and subsequent solvent evaporation from a drug–polymer solution [ 76 ] or solvent slurry [ 77 , 78 ]. In both cases, microwave heating is merely replacing traditional heating methods and hence, adds little specific benefits compared to preparative methods such as hot melt extrusion and spray drying.…”

Section: Microwave-induced In Situ Amorphizationmentioning

confidence: 99%

Microwave-Induced In Situ Amorphization: A New Strategy for Tackling the Stability Issue of Amorphous Solid Dispersions

et al. 2020

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The thermodynamically unstable nature of amorphous drugs has led to a persistent stability issue of amorphous solid dispersions (ASDs). Lately, microwave-induced in situ amorphization has been proposed as a promising solution to this problem, where the originally loaded crystalline drug is in situ amorphized within the final dosage form using a household microwave oven prior to oral administration. In addition to circumventing issues with physical stability, it can also simplify the problematic downstream processing of ASDs. In this review paper, we address the significance of exploring and developing this novel technology with an emphasis on systemically reviewing the currently available literature in this pharmaceutical arena and highlighting the underlying mechanisms involved in inducing in situ amorphization. Specifically, in order to achieve a high drug amorphicity, formulations should be composed of drugs with high solubility in polymers, as well as polymers with high hygroscopicity and good post-plasticized flexibility of chains. Furthermore, high microwave energy input is considered to be a desirable factor. Lastly, this review discusses challenges in the development of this technology including chemical stability, selection criteria for excipients and the dissolution performance of the microwave-induced ASDs.

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Electron microscopy/energy dispersive X-ray spectroscopy of drug distribution in solid dispersions and interpretation by multifractal geometry

Cited by 8 publications

References 29 publications

Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Assessment of the Extrusion Process and Printability of Suspension-Type Drug-Loaded AffinisolTM Filaments for 3D Printing

Microwave-Induced In Situ Amorphization: A New Strategy for Tackling the Stability Issue of Amorphous Solid Dispersions

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