Describing the Influence of Ball-milling on the Amorphization of Flubendazole Using the PDF and RMC Methods with X-ray Powder Diffraction Data

Bezzon, Vinícius Danilo Nonato; Pinto, Rogério da Silva; Araújo, Gabriel Lima Barros de; Lima, J.C. de; Ferreira, Fábio Furlan

doi:10.1016/j.xphs.2022.06.018

Cited by 11 publications

(4 citation statements)

References 33 publications

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“…Compared to conventional methods that include the use of organic solvents or high-energy procedures that produce a lot of waste [ 56 , 57 , 58 , 59 ], ball milling offers a “green” way to manufacture ASDs. In the literature, ball milling was used to create ASDs containing polyphenols [ 23 , 60 , 61 , 62 , 63 ] or active pharmaceutical ingredients (APIs) [ 64 , 65 , 66 , 67 ].…”

Section: Resultsmentioning

confidence: 99%

Enhanced Antioxidant and Neuroprotective Properties of Pterostilbene (Resveratrol Derivative) in Amorphous Solid Dispersions

Rosiak,

Tykarska,

Cielecka-Piontek

2024

IJMS

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In this study, amorphous solid dispersions (ASDs) of pterostilbene (PTR) with polyvinylpyrrolidone polymers (PVP K30 and VA64) were prepared through milling, affirming the amorphous dispersion of PTR via X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). Subsequent analysis of DSC thermograms, augmented using mathematical equations such as the Gordon–Taylor and Couchman–Karasz equations, facilitated the determination of predicted values for glass transition (Tg), PTR’s miscibility with PVP, and the strength of PTR’s interaction with the polymers. Fourier-transform infrared (FTIR) analysis validated interactions maintaining PTR’s amorphous state and identified involved functional groups, namely, the 4′–OH and/or –CH groups of PTR and the C=O group of PVP. The study culminated in evaluating the impact of amorphization on water solubility, the release profile in pH 6.8, and in vitro permeability (PAMPA-GIT and BBB methods). In addition, it was determined how improving water solubility affects the increase in antioxidant (ABTS, DPPH, CUPRAC, and FRAP assays) and neuroprotective (inhibition of cholinesterases: AChE and BChE) properties. The apparent solubility of the pure PTR was ~4.0 µg·mL−1 and showed no activity in the considered assays. For obtained ASDs (PTR-PVP30/PTR-PVPVA64, respectively) improvements in apparent solubility (410.8 and 383.2 µg·mL−1), release profile, permeability, antioxidant properties (ABTS: IC50 = 52.37/52.99 μg·mL−1, DPPH: IC50 = 163.43/173.96 μg·mL−1, CUPRAC: IC0.5 = 122.27/129.59 μg·mL−1, FRAP: IC0.5 = 95.69/98.57 μg·mL−1), and neuroprotective effects (AChE: 39.1%/36.2%, BChE: 76.9%/73.2%) were confirmed.

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Section: Resultsmentioning

confidence: 99%

Enhanced Antioxidant and Neuroprotective Properties of Pterostilbene (Resveratrol Derivative) in Amorphous Solid Dispersions

Rosiak,

Tykarska,

Cielecka-Piontek

2024

IJMS

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“…Since crystalline flubendazole undergoes thermal decomposition upon melting (Figure S2), the thermal-based methods of amorphization such as melt quenching are not suitable for this API . Aside from heat treatments, milling and solvent evaporation are common amorphization procedures. , In this study, mechanoactivation was employed as a “green” co-amorphization method that utilizes mechanical energy for a crystal structure decomposition without the use of solvents or other contaminants …”

Section: Resultsmentioning

confidence: 99%

“…55 Aside from heat treatments, milling and solvent evaporation are common amorphization procedures. 56,57 In this study, mechanoactivation was employed as a "green" co-amorphization method that utilizes mechanical energy for a crystal structure decomposition without the use of solvents or other contaminants. 58 At the first step, FluBZ was ground in a planetary mill for different periods of time, and the product was immediately analyzed by PXRD.…”

Section: Mechanochemical Screening For Amorphous and Co-amorphous Formsmentioning

confidence: 99%

Influence of Co-amorphization on the Physical Stability and Dissolution Performance of an Anthelmintic Drug Flubendazole

et al. 2023

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In this work, the co-amorphization approach was applied to flubendazole (FluBZ), resulting in the formation of two novel solid forms of FluBZ with l-phenylalanine (Phe) and l-tryptophan (Trp). A variety of physicochemical techniques have been used to describe new systems, including powder X-ray diffraction, thermal methods, infrared spectroscopy, and scanning electron microscopy. Co-amorphization has been shown to suppress crystallization tendency and considerably increase the shelf-life storage of amorphous flubendazole solid across a wide range of relative humidities. The dissolution behavior of the amorphous forms in biorelevant media at pH = 1.6, pH = 6.5, and 37 °C has been studied in terms of C max (maximum FluBZ concentration), T max (time to attain peak drug concentration), and AUC (concentration area under the curve during dissolution). At pH = 6.5, a continuous supersaturation and the highest AUC value of all examined systems were observed for the FluBZ-Phe (1:1) system. The phase solubility diagrams revealed that the reason for the better dissolution performance of FluBZ-Phe (1:1) at pH = 6.5 is a complexation between the components in a solution. This work highlights the applicability of co-amorphous systems in improving the physical stability and dissolution performance of drug compounds with poor biopharmaceutical characteristics.

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“…Other than by rapidly cooling a melt, amorphization can also be achieved (intentionally or unintentionally) by direct transformations from crystalline to amorphous forms during processes such as mechanical grinding, micronization, compression, granulation and drying (Bezzon et al, 2022;Feng et al, 2008;Modhave et al, 2020). Mechanical grinding by means of vibrational ball milling is a common procedure for particle size reduction (Michalchuk et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Amorphization of different furosemide polymorphic forms during ball milling: tracking solid-to-solid phase transformations

Wang

Gong

Rades

et al. 2023

Preprint

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Ball milling is used, not only to reduce the particle size of pharmaceutical powders, but also to induce changes in the physical properties of drugs. In this work we prepared three crystal forms of furosemide (forms Ⅰ, Ⅱ, and Ⅲ) and studied their solid phase transformations during ball milling. Powder X-ray diffraction and modulated differential scanning calorimetry were used to characterize the samples after each milling time on their path to amorphization. Our results show that forms Ⅰ and III directly converted into an amorphous phase, while form Ⅱ first undergoes a polymorphic transition to form Ⅰ, and then gradually loses its crystallinity, finally reaching full amorphousness. During ball milling of forms Ⅰ and Ⅱ, the glass transition temperature (Tg) of the amorphous fraction of the milled material remains almost unchanged at 75℃ and 74℃, respectively (whilst the amorphous content increases). In contrast, the Tg values of the amorphous fraction of milled form III increase with increasing milling times, from 63℃ to 71℃, indicating an unexpected phenomenon of amorphous-to-amorphous transformation. The amorphous fraction of milled forms I and II samples presented a longer structural relaxation (i.e., lower molecular mobility) than the amorphous fraction of milled form III samples. Moreover, the structural relaxation time remained the same for the increasing amorphous fraction during milling of forms I and II. In contrast, the structural relaxation times were always shorter for the amorphous fraction of form III, but increased with increasing amorphous content during milling, confirming amorphous-to-amorphous transformation.

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Describing the Influence of Ball-milling on the Amorphization of Flubendazole Using the PDF and RMC Methods with X-ray Powder Diffraction Data

Cited by 11 publications

References 33 publications

Enhanced Antioxidant and Neuroprotective Properties of Pterostilbene (Resveratrol Derivative) in Amorphous Solid Dispersions

Enhanced Antioxidant and Neuroprotective Properties of Pterostilbene (Resveratrol Derivative) in Amorphous Solid Dispersions

Influence of Co-amorphization on the Physical Stability and Dissolution Performance of an Anthelmintic Drug Flubendazole

Amorphization of different furosemide polymorphic forms during ball milling: tracking solid-to-solid phase transformations

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