Crystallization of Indomethacin from the Amorphous State below and above Its Glass Transition Temperature

Yoshioka, Minoru; Hancock, Bruno C.; Zografi, George

doi:10.1002/jps.2600831211

Cited by 435 publications

(353 citation statements)

References 20 publications

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“…Two polymorphs (α and γ) can crystallize at the surface of an IMC glass. The structures of these polymorphs are known (23,24) and both are denser than the glass (25). Fig.…”

Section: Resultsmentioning

confidence: 94%

“…From data on 10 films of different thicknesses, the index of refraction of the IMC glass at 20°C was found to be: nðλÞ ¼ A þ B∕λ 2 þ C∕λ 4 , where λ is the wavelength in nanometers (400-1,000 nm), A ¼ 1.601 AE 0.003, B ¼ 0.013 AE 0.002, and C ¼ 0.0007 AE 0.0003. For QCM, a film was coated directly on the QCM sensor and its thickness was calculated from the mass reported by the QCM, the sensor area, and the density of IMC glass (1.31 g∕cm 3 ) (25).…”

Section: Methodsmentioning

confidence: 99%

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Glasses crystallize rapidly at free surfaces by growing crystals upward

Sun

Zhu

Kearns

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

122

137

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The crystallization of glasses and amorphous solids is studied in many fields to understand the stability of amorphous materials, the fabrication of glass ceramics, and the mechanism of biomineralization. Recent studies have found that crystal growth in organic glasses can be orders of magnitude faster at the free surface than in the interior, a phenomenon potentially important for understanding glass crystallization in general. Current explanations differ for surface-enhanced crystal growth, including released tension and enhanced mobility at glass surfaces. We report here a feature of the phenomenon relevant for elucidating its mechanism: Despite their higher densities, surface crystals rise substantially above the glass surface as they grow laterally, without penetrating deep into the bulk. For indomethacin (IMC), an organic glass able to grow surface crystals in two polymorphs (α and γ), the growth front can be hundreds of nanometers above the glass surface. The process of surface crystal growth, meanwhile, is unperturbed by eliminating bulk material deeper than some threshold depth (ca. 300 nm for α IMC and less than 180 nm for γ IMC). As a growth strategy, the upward-lateral growth of surface crystals increases the system's surface energy, but can effectively take advantage of surface mobility and circumvent slow growth in the bulk. C rystallization is a ubiquitous process, producing countless solids in the natural and man-made world. Glasses and amorphous solids are formed by avoiding crystallization while cooling liquids, condensing vapors, or drying solutions. The solidity of a glass might suggest resistance to crystallization; its very existence implies that crystallization is avoidable. And yet glasses can crystallize, sometimes surprisingly fast. The crystallization of glasses is of interest in many fields for understanding the stability of amorphous materials (1), the fabrication of glass ceramics, and the mechanism of biomineralization, for which crystallization of amorphous solid precursors is considered a key step (2).Recent studies have discovered that different modes of crystal growth can emerge as a liquid is cooled to form a glass (3-8), causing crystal growth fronts to advance at velocities much faster than predicted by standard theories. One such growth mode [the glass-to-crystal (GC) mode] exists in the bulk and can cause an increase of crystal growth rate by a factor of 10 4 with a temperature drop by a few kelvin (3, 4). Another new growth mode occurs at the free surface and can lead to much faster crystal growth than in the bulk (5-8). Although these phenomena have been observed prominently in organic glasses, they may be relevant for understanding glass crystallization in general. These phenomena seem to have counterparts in nonorganic glasses, but differences are also evident. Fast crystal growth is known for metallic glasses and amorphous silicon, but the abrupt activation of GC growth is reported only for organic glasses. Surface-enhanced crystal growth occurs in amorphous selenium ...

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“…Two polymorphs (α and γ) can crystallize at the surface of an IMC glass. The structures of these polymorphs are known (23,24) and both are denser than the glass (25). Fig.…”

Section: Resultsmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Glasses crystallize rapidly at free surfaces by growing crystals upward

Sun

Zhu

Kearns

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

122

137

View full text Add to dashboard Cite

show abstract

“…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 .…”

Section: Introductionmentioning

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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“…The amorphous forms of drugs like indomethacin and phenobarbital have shown crystallization at temperatures well below their respective glass transition temperatures, indicating a high molecular mobility of the amorphous solids [5][6][7][8]. In addition to the elevated storage temperatures, water has also been reported to be detrimental to the physical stability of the amorphous solids [9].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mobility and Physical Stability of Amorphous Irbesartan

Chawla

2009

Sci. Pharm.

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Amorphous systems have attracted considerable attention due to their favorable properties; however, their stability issues still pose a major challenge. The purpose of the present work was to investigate the role of molecular mobility and moisture in the physical stability of a selected pharmaceutical amorphous system. Irbesartan (IBS), a relatively stable glass, was chosen as the model drug, as it exhibits a good physical stability (resistance to crystallization) at temperatures below the glass transition (T g -50 K). The amorphous system was annealed at temperatures 298 K (25 °C) and 313 K (40 °C) at 0 and 75 % RH to study the effect of temperature and moisture on its relaxation behavior. Differential scanning calorimetry (DSC) was used to characterize both the crystalline and the freshly prepared glass, and to monitor the extent of relaxation at temperatures below glass transition (Tg) as well as heat capacity changes as a function of temperature. Molecular relaxation time constant (τ) decreased drastically from 302 years to 68 hours with the increase in annealing temperature as determined by Kohlrausch-William-Watts (KWW) equation. IBS was found to be 'relatively' stable in the amorphous state and presented a challenge for temporal measurements. Hence, at low annealing temperatures, (T g -50 K or below) initial relaxation time (τ 0 ) was estimated using the calorimetric based approach. Amorphous IBS was non-hygroscopic and retained its glassy nature under the accelerated stability conditions. The extent of relaxation in the amorphous drug in the presence of moisture was also estimated.

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Crystallization of Indomethacin from the Amorphous State below and above Its Glass Transition Temperature

Cited by 435 publications

References 20 publications

Glasses crystallize rapidly at free surfaces by growing crystals upward

Glasses crystallize rapidly at free surfaces by growing crystals upward

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

Molecular Mobility and Physical Stability of Amorphous Irbesartan

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