Dielectric Study of Equimolar Acetaminophen–Aspirin, Acetaminophen–Quinidine, and Benzoic Acid–Progesterone Molecular Alloys in the Glass and Ultraviscous States and Their Relevance to Solubility and Stability

Johari, G. P.; Kim, S.; Shanker, Ravi

doi:10.1002/jps.21930

Cited by 27 publications

(24 citation statements)

References 62 publications

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“…The JG process is believed to be the precursor of structural relaxation 51 . The JG process is believed to be the precursor of structural relaxation 51 .…”

Section: Dielectric Relaxation Studies Of Ezetimibe In the Glassy Statementioning

confidence: 99%

Physical Stability of the Amorphous Anticholesterol Agent (Ezetimibe): The Role of Molecular Mobility

et al. 2014

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The purpose of this paper is to examine the role of molecular mobility in the recrystallization process from the amorphous state of the anticholesterol drug ezetimibe. Both the molecular dynamics and crystallization kinetics have been studied using various experimental techniques, such as broadband dielectric spectroscopy (BDS), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Our investigations have shown that ezetimibe easily recrystallizes from the disordered state, both below and above its glass transition temperature (Tg = 336 K). Moreover, we found that an only slightly elevated pressure (5 MPa) significantly accelerates the recrystallization process at T > Tg. We predict that the structural relaxation time of amorphous ezetimibe at 293 K (storage temperature) and ambient pressure is only 22 days. This result corresponds to the characteristic time, determined from XRD measurements, for amorphous ezetimibe to recrystallize during storage at Troom = 298 K. It leads to the conclusion that the molecular mobility reflected in structural relaxation of ezetimibe is mainly responsible for devitrification of this drug. Finally, we determined a relatively easy way to improve the physical stability of the drug by preparing a binary amorphous ezetimibe-Soluplus mixture. Ezetimibe in an amorphous mixture with 20 wt % Soluplus has a much better (over six times) solubility than the pure crystalline material.

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“…The JG process is believed to be the precursor of structural relaxation 51 . The JG process is believed to be the precursor of structural relaxation 51 .…”

Section: Dielectric Relaxation Studies Of Ezetimibe In the Glassy Statementioning

confidence: 99%

Physical Stability of the Amorphous Anticholesterol Agent (Ezetimibe): The Role of Molecular Mobility

et al. 2014

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“…7,8,9,10 It is believed that the main factor affecting physical stability of disordered APIs is molecular mobility 11,12 . It has been demonstrated many times that the most efficient experimental tool to investigate molecular dynamics of glass-forming systems is broadband dielectric spectroscopy (BDS) 13,14 . This technique enables the determination of the characteristic time of molecular reorientation over a broad range of frequencies (over 12 decades) and temperatures.…”

Section: Introductionmentioning

confidence: 99%

“…37 The X(T) 13 dependence, for each heating rate, is presented in Figure 6a, and was obtained by using the following equation:…”

mentioning

confidence: 99%

Molecular Dynamics and Physical Stability of Amorphous Nimesulide Drug and Its Binary Drug–Polymer Systems

et al. 2016

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In this paper we study the effectiveness of three well known polymers: inulin, Soluplus and PVP in stabilizing amorphous form of nimesulide (NMS) drug. The recrystallization tendency of pure drug as well as measured drug-polymer systems were examined at isothermal conditions by using broadband dielectric spectroscopy (BDS), and at non-isothermal conditions by differential scanning calorimetry (DSC). Our investigation has shown that the crystallization half-life time of pure NMS at 328 K is equal to 33 minutes. We found that this time can be prolonged to 40 years after adding to NMS 20% of PVP polymer.This polymer proved to be the best NMS's stabilizer, while the worst stabilization effect was found after adding the inulin to NMS. Additionally, our DSC, BDS and FTIR studies indicate that for suppression of NMS's re-crystallization in NMS-PVP system, the two mechanisms are responsible: the polymeric steric hindrances as well as the antiplastization effect excerted by the excipient.

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“…More recently, studies of the molecular mobility in aqueous glasses were extended beyond the T g and alpha-relaxation, to include fast and less-cooperative mobility modes, in particular Johari-Goldstein beta-relaxation. [5][6][7][8] A comprehensive picture of the molecular mobility landscape is emerging, with the potential energy surface introduced to describe both the intramolecular and intermolecular features of disordered solids. 9 A potential practical utility of the potential energy surface has also been demonstrated, by using high-powered terahertz pulses to induce crystallization and preferential growth of crystalline polymorphs in glasses.…”

Section: Introductionmentioning

confidence: 99%

Freezing of Aqueous Solutions and Chemical Stability of Amorphous Pharmaceuticals: Water Clusters Hypothesis

Shalaev

Soper

Zeitler

et al. 2019

Journal of Pharmaceutical Sciences

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Molecular mobility has been traditionally invoked to explain physical and chemical stability of diverse pharmaceutical systems. Although the molecular mobility concept has been credited with creating a scientific basis for stabilization of amorphous pharmaceuticals and biopharmaceuticals, it has become increasingly clear that this approach represents only a partial description of the underlying fundamental principles. An additional mechanism is proposed herein to address 2 key questions: (1) the existence of unfrozen water (i.e., partial or complete freezing inhibition) in aqueous solutions at subzero temperatures and (2) the role of water in the chemical stability of amorphous pharmaceuticals. These apparently distant phenomena are linked via the concept of water clusters. In particular, freezing inhibition is associated with the confinement of water clusters in a solidified matrix of an amorphous solute, with nanoscaled water clusters being observed in aqueous glasses using wide-angle neutron scattering. The chemical instability is suggested to be directly related to the catalysis of proton transfer by water clusters, considering that proton transfer is the key elementary reaction in many chemical processes, including such common reactions as hydrolysis and deamidation.

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Dielectric Study of Equimolar Acetaminophen–Aspirin, Acetaminophen–Quinidine, and Benzoic Acid–Progesterone Molecular Alloys in the Glass and Ultraviscous States and Their Relevance to Solubility and Stability

Cited by 27 publications

References 62 publications

Physical Stability of the Amorphous Anticholesterol Agent (Ezetimibe): The Role of Molecular Mobility

Physical Stability of the Amorphous Anticholesterol Agent (Ezetimibe): The Role of Molecular Mobility

Molecular Dynamics and Physical Stability of Amorphous Nimesulide Drug and Its Binary Drug–Polymer Systems

Freezing of Aqueous Solutions and Chemical Stability of Amorphous Pharmaceuticals: Water Clusters Hypothesis

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