Does the molecular mobility and flexibility of the saccharide ring affect the glass-forming ability of naproxen in binary mixtures?

Minecka, Aldona; Kamińska, Ewa; Tarnacka, Magdalena; Jurkiewicz, Karolina; Talik, Agnieszka; Wolnica, Kamila; Dulski, Mateusz; Kasprzycka, Anna; Spychalska, Patrycja; Garbacz, Grzegorz; Kamiński, Kamil; Paluch, Marian

doi:10.1016/j.ejps.2019.105091

Cited by 6 publications

(4 citation statements)

References 54 publications

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“…The origin of structural relaxation is considered to be the synergistic movement between molecules, and α-relaxation plays a leading role in structural relaxation and molecular mobility because it involves a wide range of particle movements [ 62 , 63 ]. The dielectric spectroscopy was performed to investigate the molecular mobility of CUR-MAG CM in the presence and absence of very little polymer additives.…”

Section: Resultsmentioning

confidence: 99%

“…In the ternary co-amorphous systems, no α-relaxation occurred at 16, 24, and 32 °C and α-relaxation only occurred at 40 °C in the detected frequency range ( Figure 11 B–D). As compared with CUR-MAG CM, the α-relaxation process of the ternary co-amorphous systems shifted from high frequency to low frequency at 40 °C in the order of CUR-MAG CM, CUR-MAG-HPC CM, CUR-MAG-HPMC CM, and CUR-MAG-PVP K30 CM, indicating that a small amount of polymer addition significantly inhibited the molecular mobility of CUR-MAG CM [ 63 ].…”

Section: Resultsmentioning

confidence: 99%

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Deaggregation and Crystallization Inhibition by Small Amount of Polymer Addition for a Co-Amorphous Curcumin-Magnolol System

Han

et al. 2021

Pharmaceutics

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Different from previously reported co-amorphous systems, a co-amorphous curcumin-magnolol (CUR-MAG CM) system, as compared with its crystalline counterparts, exhibited decreased dissolution due to its aggregation during dissolution. The main purpose of the present study is to deaggregate CUR-MAG CM to optimize drug dissolution and explore the deaggregation mechanism involved. Herein, a small amount of polymer (HPMC, HPC, and PVP K30) was co-formulated at 5% (w/w) with CUR-MAG CM as ternary co-amorphous systems. The polymer addition changed the surface properties of CUR-MAG CM including improved water wettability enhanced surface free energy, and hence exerted a deaggregating effect. As a result, the ternary co-amorphous systems showed faster and higher dissolution as compared with crystalline CUR/MAG and CUR-MAG CM. In addition, the nucleation and crystal growth of dissolved CUR and MAG molecules were significantly inhibited by the added polymer, maintaining a supersaturated concentration for a long time. Furthermore, polymer addition increased the Tg of CUR-MAG CM, potentially involving molecular interactions and inhibiting molecular mobility, resulting in enhanced physical stability under 25 °C/60% RH and 40 °C/75% RH conditions. Therefore, this study provides a promising strategy to optimize the dissolution and physical stability of co-amorphous systems by deaggregation and crystallization inhibition via adding small amounts of polymers.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Deaggregation and Crystallization Inhibition by Small Amount of Polymer Addition for a Co-Amorphous Curcumin-Magnolol System

Han

et al. 2021

Pharmaceutics

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“…As a consequence, the advantages given by the amorphous state are lost during storage . The most convenient way to stabilize amorphous APIs is mixing them with various excipients, i.e., modified mono-, di, and oligosaccharides, ,− polymers, − and amino acids. − In such case, so-called coamorphous systems of enhanced physical stability are created. The other unique alternative to affect and stabilize disordered pharmaceuticals is infiltration them into porous templates made of inert, biocompatible, nontoxic materials composed of pores of varying geometry, morphology, and size ( d ), considered as 2D confinement …”

Section: Introductionmentioning

confidence: 99%

Anormal Thermal History Effect on the Structural Dynamics of Probucol Infiltrated into Porous Alumina

et al. 2021

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Herein, broadband dielectric (BDS) and Fourier transform infrared spectroscopy (FTIR), together with differential scanning calorimetry (DSC) and X-ray diffraction (XRD), were applied to study the molecular dynamics, molecular interactions as well as physical stability of an amorphous Active Pharmaceutical Ingredient (API) probucol (PRO)infiltrated into anodic aluminum oxide (AAO) membranes of pore size, d ∼ 10−160 nm. Interestingly, the behavior of examined substance strongly depends on the applied thermal protocol. Remarkably, for the first time, we observed that the structural dynamics of the slowly cooled PRO under confinement is significantly enhanced when compared to that of the quenched material. This unusual behavior was interpreted as a result of surface-induced effects (including the formation of well-resolved interfacial H-bonded layer and adsorption− desorption processes near the interface) that are magnified by the extremely high sensitivity to density fluctuation of studied PRO, reflected in the enormous pressure coefficient of the glass transition temperature dT g /dp = 427 K/GPa. In fact, FTIR investigations revealed that PRO tends to self-associate under confinement and forms a strongly bonded interfacial layer, which controls the variation in the structural dynamics of core molecules. Finally, we observed that the tendency to crystallize of confined API is reduced with respect to the bulk, even though the critical size of PRO nuclei (r c ∼ 3 nm) is significantly lower than the smallest examined pore size. Nevertheless, after few weeks of storage, the investigated substance crystallized in larger pores, while it remained stable in the nanochannels of d = 10 nm. A combination of XRD and DSC measurements indicated that the infiltrated PRO forms two polymorphs, the stable form I (dominating in bulk) and unstable form II (prevailing under confinement). That means that porous matrices might be used to obtain and maintain prolonged stability of unstable polymorphic forms of API.

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“…It is due to a difference in the T g of neat components of the binary systems. Importantly, the presence of a single glass transition temperature in all examined SDs suggests their homogeneity. − However, since nearly the same pattern of behavior has been shown in literature also for the heterogeneous systems, , we have performed additional dielectric measurements to make sure that the investigated mixtures are indeed homogeneous. Another purpose of these studies was to characterize the molecular dynamics of the prepared SDs.…”

Section: Resultsmentioning

confidence: 71%

Influence of the Internal Structure and Intermolecular Interactions on the Correlation between Structural (α) and Secondary (β-JG) Relaxation below the Glass Transition Temperature in Neat Probucol and Its Binary Mixtures with Modified Saccharides

et al. 2020

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Broadband dielectric spectroscopy (BDS) has been used to study the molecular dynamics and aging process in neat probucol (PRO) as well as its binary mixtures with selected acetylated saccharides. In particular, we applied the Casalini and Roland approach to determine structural relaxation times in the glassy state of the examined systems (so-called isostructural times, τ iso ). Next, using the calculated τ iso , primitive relaxation times of the coupling model were obtained and compared to the experimental secondary β (Johari–Goldstein (JG) type) relaxation times. Interestingly, it turned out that there is a correlation between the β-JG and the structural (α)-relaxation processes below the glass transition temperature (T < T g) in each investigated sample. This is a new observation compared to previous studies demonstrating that such a relationship exists only in the supercooled liquid state of neat PRO. Moreover, it was revealed that the stretching parameters obtained from the aging procedure are very close to the ones determined by fitting the dielectric data above the T g with the use of the Kohlrausch–Williams–Watts function, indicating that the aging process is governed by the α-relaxation. Complementary Fourier transform infrared and X-ray diffraction measurements allowed us to find a possible reason for these findings. It was demonstrated that although there are very weak intermolecular interactions between PRO and modified saccharides, the intra- and intermolecular structure of PRO is practically unaffected by the presence of modified saccharides.

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Does the molecular mobility and flexibility of the saccharide ring affect the glass-forming ability of naproxen in binary mixtures?

Cited by 6 publications

References 54 publications

Deaggregation and Crystallization Inhibition by Small Amount of Polymer Addition for a Co-Amorphous Curcumin-Magnolol System

Deaggregation and Crystallization Inhibition by Small Amount of Polymer Addition for a Co-Amorphous Curcumin-Magnolol System

Anormal Thermal History Effect on the Structural Dynamics of Probucol Infiltrated into Porous Alumina

Influence of the Internal Structure and Intermolecular Interactions on the Correlation between Structural (α) and Secondary (β-JG) Relaxation below the Glass Transition Temperature in Neat Probucol and Its Binary Mixtures with Modified Saccharides

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