A New Method To Identify Physically Stable Concentration of Amorphous Solid Dispersions (I): Case of Flutamide + Kollidon VA64

Chmiel, Krzysztof; Knapik-Kowalczuk, Justyna; Jurkiewicz, Karolina; Sawicki, Wiesław; Jachowicz, Renata; Paluch, Marian

doi:10.1021/acs.molpharmaceut.7b00382

Cited by 42 publications

(62 citation statements)

References 34 publications

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“…These benefits, however, come at a risk. The high internal energy of amorphous solids, which, on the one hand, is the reason for their high solubility, on the other hand, makes amorphous materials thermodynamically unstable [10][11][12][13][14]. Thus, currently, much effort is being made to (i) investigate physical stability of amorphous form of pharmaceuticals [15][16][17], (ii) find effective methods leading to their stabilization [18][19][20], and (iii) discover the molecular mechanisms responsible for the observed recrystallization inhibition [16,[21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Importance of Mesoporous Silica Particle Size in the Stabilization of Amorphous Pharmaceuticals—The Case of Simvastatin

et al. 2020

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In this paper, the role of mesoporous silica (MS) particle size in the stabilization of amorphous simvastatin (SVT) is revealed. For inhibiting recrystallization of the supercooled drug, the two MS materials (Syloid® XDP 3050 and Syloid® 244 FP) were employed. The crystallization tendency of SVT alone and in mixture with the MS materials was investigated by Differential Scanning Calorimetry (DSC) and Broadband Dielectric Spectroscopy (BDS). Neither confinement of the SVT molecules inside the MS pores nor molecular interactions between functional groups of the SVT molecules and the surface of the stabilizing excipient could explain the observed stabilization effect. The stabilization effect might be correlated with diffusion length of the SVT molecules in the MS materials that depended on the particle size. Moreover, MS materials possessing different particle sizes could offer free spaces with different sizes, which might influence crystal growth of SVT. All of these factors must be considered when mesoporous materials are used for stabilizing pharmaceutical glasses.

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Section: Introductionmentioning

confidence: 99%

Importance of Mesoporous Silica Particle Size in the Stabilization of Amorphous Pharmaceuticals—The Case of Simvastatin

et al. 2020

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“…Recently, the change of real parts of the complex dielectric permittivity obtained from broadband dielectric spectroscopy can be used to characterize the crystallization of amorphous formulations to a certain extent 59. , 60. .…”

Section: Physicochemical Characteristics Of Coamorphous Systemsmentioning

confidence: 99%

Advances in coamorphous drug delivery systems

Shi

Moinuddin

Cai

2019

Acta Pharmaceutica Sinica B

141

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In recent years, the coamorphous drug delivery system has been established as a promising formulation approach for delivering poorly water-soluble drugs. The coamorphous solid is a single-phase system containing an active pharmaceutical ingredient (API) and other low molecular weight molecules that might be pharmacologically relevant APIs or excipients. These formulations exhibit considerable advantages over neat crystalline or amorphous material, including improved physical stability, dissolution profiles, and potentially enhanced therapeutic efficacy. This review provides a comprehensive overview of coamorphous drug delivery systems from the perspectives of preparation, physicochemical characteristics, physical stability, in vitro and in vivo performance. Furthermore, the challenges and strategies in developing robust coamorphous drug products of high quality and performance are briefly discussed.

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“…Therefore, we performed the solubility limit studies. It was recently shown that broadband dielectric spectroscopy (BDS) can be successfully utilized to determine the solubility limits of a drug dissolved within the polymer matrix [16,[28][29][30][31][32]. Since the non-isothermal measurements are, without a doubt, significantly less time-consuming than isothermal ones, and at the same time they provide consistent results [16,28,29], we decided to proceed with the protocol proposed in Reference [16].…”

Section: Solubility Limit Studiesmentioning

confidence: 99%

Compression-Induced Phase Transitions of Bicalutamide

et al. 2020

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The formation of solid dispersions with the amorphous drug dispersed in the polymeric matrix improves the dissolution characteristics of poorly soluble drugs. Although they provide an improved absorption after oral administration, the recrystallization, which can occur upon absorption of moisture or during solidification and other formulation stages, serves as a major challenge. This work aims at understanding the amorphization-recrystallization changes of bicalutamide. Amorphous solid dispersions with poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA) were obtained by either ball milling or spray drying. The applied processes led to drug amorphization as confirmed using X-ray diffraction and differential scanning calorimetry. Due to a high propensity towards mechanical activation, the changes of the crystal structure of physical blends of active pharmaceutical ingredient (API) and polymer upon pressure were also examined. The compression led to drug amorphization or transition from form I to form II polymorph, depending on the composition and applied force. The formation of hydrogen bonds confirmed using infrared spectroscopy and high miscibility of drug and polymer determined using non-isothermal dielectric measurements contributed to the high stability of amorphous solid dispersions. They exhibited improved wettability and dissolution enhanced by 2.5- to 11-fold in comparison with the crystalline drug. The drug remained amorphous upon compression when the content of PVP/VA in solid dispersions exceeded 20% or 33%, in the case of spray-dried and milled systems, respectively.

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A New Method To Identify Physically Stable Concentration of Amorphous Solid Dispersions (I): Case of Flutamide + Kollidon VA64

Cited by 42 publications

References 34 publications

Importance of Mesoporous Silica Particle Size in the Stabilization of Amorphous Pharmaceuticals—The Case of Simvastatin

Importance of Mesoporous Silica Particle Size in the Stabilization of Amorphous Pharmaceuticals—The Case of Simvastatin

Advances in coamorphous drug delivery systems

Compression-Induced Phase Transitions of Bicalutamide

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