The Slow Molecular Mobility in Amorphous Ketoprofen and Ibuprofen

Mora, Elsa; Diogo, Hermı́nio P.; Ramos, Joaquim J. Moura

doi:10.1002/jps.24591

Cited by 8 publications

(3 citation statements)

References 60 publications

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“…The onset of the peak indicates that the melting point of raw KET is equal to 94 °C, which stays in agreement with Tiţa et al [ 40 ]. Since the drug is characterized by very low glass transition temperature (T g below 0 °C) [ 42 ], its amorphization and physical stability of the molecularly disordered state are realized as challenging. The value of glass transition temperature measured for raw, quench-cooled ketoprofen is equal to −2 °C.…”

Section: Resultsmentioning

confidence: 99%

How to Obtain the Maximum Properties Flexibility of 3D Printed Ketoprofen Tablets Using Only One Drug-Loaded Filament?

et al. 2021

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The flexibility of dose and dosage forms makes 3D printing a very interesting tool for personalized medicine, with fused deposition modeling being the most promising and intensively developed method. In our research, we analyzed how various types of disintegrants and drug loading in poly(vinyl alcohol)-based filaments affect their mechanical properties and printability. We also assessed the effect of drug dosage and tablet spatial structure on the dissolution profiles. Given that the development of a method that allows the production of dosage forms with different properties from a single drug-loaded filament is desirable, we developed a method of printing ketoprofen tablets with different dose and dissolution profiles from a single feedstock filament. We optimized the filament preparation by hot-melt extrusion and characterized them. Then, we printed single, bi-, and tri-layer tablets varying with dose, infill density, internal structure, and composition. We analyzed the reproducibility of a spatial structure, phase, and degree of molecular order of ketoprofen in the tablets, and the dissolution profiles. We have printed tablets with immediate- and sustained-release characteristics using one drug-loaded filament, which demonstrates that a single filament can serve as a versatile source for the manufacturing of tablets exhibiting various release characteristics.

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Section: Resultsmentioning

confidence: 99%

How to Obtain the Maximum Properties Flexibility of 3D Printed Ketoprofen Tablets Using Only One Drug-Loaded Filament?

et al. 2021

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“…It should be noted that the TSDC behavior shown in Figure 7, described and interpreted above, is a universal behavior also observed in the physical aging of the α-relaxation in low molecular weight glass-formers with very diverse molecular structures. 8,11,[58][59][60][61][62] However, the preceding analysis refers to a specific motional mode of the main relaxation, the one that corresponds to the peak of maximum intensity in Figure 3(b); this is a poorly distributed mobility, as it was isolated through a narrow polarization window TSDC experiment. The main relaxation, however, is a widely distributed relaxation, consisting of different motional modes whose kinetic parameters differ significantly from each other.…”

Section: Aging Effect On the Main Relaxationmentioning

confidence: 99%

Dielectric relaxation study of poly (ether imide) by thermally stimulated depolarization currents

Diogo

2021

J of Applied Polymer Sci

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This work presents a detailed study, by thermostimulated depolarization currents, of the molecular mobility of poly (ether imide) in a broad temperature range covering the amorphous solid state, the glass transition, and the rubber state. Taking advantage of the very wide distribution of motional modes of the PEI glass transition (the broadest of all known glass formers), we carried out an in-depth study of physical aging involving different modes, which provided a more comprehensive view of the aging process. We also analyzed in detail the mobility below T g where, in addition to the fast secondary relaxation, we identified a Johari-Goldstein. In the rubber state, on the other hand, we detected a mobility but showed that it corresponds to space charge motions rather to dipolar reorientations.

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“…However, recent measurements found it relatively stable with respect to recrystallization 20 K above T g . Moreover, and perhaps more importantly, we selected this compound for our investigation since experimental and computational data are both available for the crystal and for the amorphous form. − This favorable condition allows us to quantitatively test the validity of a new approach to compute absolute free energies by first performing thermodynamic integration (TI , ) to connect the harmonic to the anharmonic free energy at relatively low temperature, followed by another TI step to increase temperature to the value of interest. The new approach, which relies also on the optimal approximation of the system free energy by a harmonic Hamiltonian, overcomes the major limitation of previous methods, , arising from the diffusion of the solvent molecules.…”

Section: Introductionmentioning

confidence: 99%

Solubility Advantage of Amorphous Ketoprofen. Thermodynamic and Kinetic Aspects by Molecular Dynamics and Free Energy Approaches

Gobbo

Ballone

Decherchi

et al. 2020

J. Chem. Theory Comput.

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Thermodynamic and kinetic aspects of crystalline (c-KTP) and amorphous (a-KTP) ketoprofen dissolution in water have been investigated by molecular dynamics simulation focusing on free energy properties. Absolute free energies of all relevant species and phases have been determined by thermodynamic integration on a novel path, first connecting the harmonic to the anharmonic system Hamiltonian at low T and then extending the result to the temperature of interest. The free energy required to transfer one ketoprofen molecule from the crystal to the solution is in fair agreement with the experimental value. The absolute free energy of the amorphous form is 19.58 kJ/mol higher than for the crystal, greatly enhancing the ketoprofen concentration in water, although as a metastable species in supersaturated solution. The kinetics of the dissolution process has been analyzed by computing the free energy profile along a reaction coordinate bringing one ketoprofen molecule from the crystal or amorphous phase to the solvated state. This computation confirms that, compared to the crystal form, the dissolution rate is nearly 7 orders of magnitude faster for the amorphous form, providing one further advantage to the latter in terms of bioavailability. The problem of drug solubility, of great practical importance, is used here as a test bed for a refined method to compute absolute free energies, which could be of great interest in biophysics and drug discovery in particular.

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The Slow Molecular Mobility in Amorphous Ketoprofen and Ibuprofen

Cited by 8 publications

References 60 publications

How to Obtain the Maximum Properties Flexibility of 3D Printed Ketoprofen Tablets Using Only One Drug-Loaded Filament?

How to Obtain the Maximum Properties Flexibility of 3D Printed Ketoprofen Tablets Using Only One Drug-Loaded Filament?

Dielectric relaxation study of poly (ether imide) by thermally stimulated depolarization currents

Solubility Advantage of Amorphous Ketoprofen. Thermodynamic and Kinetic Aspects by Molecular Dynamics and Free Energy Approaches

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