Role of Thermodynamic, Molecular, and Kinetic Factors in Crystallization from the Amorphous State

Bhugra, Chandan; Pikal, Michael J.

doi:10.1002/jps.21138

Cited by 387 publications

(337 citation statements)

References 85 publications

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“…8). The replicate measurements were performed in slightly different temperatures, which might explain observed between measurements, since crystallization is known to be temperature dependent (Bhugra and Pikal, 2008). In the present study, increasing the temperature caused the rate of crystallization to increase as measured with Raman.…”

Section: Recrystallization Of Xylitol and Xylitol-silica Solid Dispermentioning

confidence: 54%

“…8 and 9). This can be attributed to the temperature dependence of crystal growth (Bhugra and Pikal, 2008), since the ambient temperature during Raman measurements in ambient conditions was clearly lower than during the WAXS-experiments and Raman experiments in elevated temperature. Based on the WAXS results, the rate of crystallization was slower for the solid dispersion, opposite to the Raman measurements (Fig.…”

Section: Recrystallization Of Xylitol and Xylitol-silica Solid Dispermentioning

confidence: 93%

“…In the present study, increasing the temperature caused the rate of crystallization to increase as measured with Raman. Increasing the temperature increases molecular motion and reduces viscosity, which both favor crystallization (Bhugra and Pikal, 2008;Yu, 2016). When the temperature was increased from T = 21 C to T = 29 C, the difference in rate of crystallization between pure xylitol and xylitol-silica dispersion became less significant.…”

Section: Recrystallization Of Xylitol and Xylitol-silica Solid Dispermentioning

confidence: 99%

“…Considerable effort and resources have been invested in trying to achieve amorphous formulations with high enough stability to ensure sufficient physical stability of the active pharmaceutical ingredient throughout the shelf life of the final product. Still, a complete understanding of the crystallization of amorphous solids has not been achieved Bhugra and Pikal, 2008). Typical stability studies of pharmaceuticals take several months to complete, and in order to facilitate the development of drug products to the market there is a need to be able to rapidly screen the physical stability challenges of amorphous drugs.…”

Section: Introductionmentioning

confidence: 99%

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Monitoring the recrystallisation of amorphous xylitol using Raman spectroscopy and wide-angle X-ray scattering

Palomäki

Ahvenainen

Ehlers

et al. 2016

International Journal of Pharmaceutics

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Chemical compounds studied in this article: Xylitol (PubChem CID 6912) Silica (PubMed CID 24261) Ibuprofen (PubChem CID 3672) Indomethacin (PubChem CID 3715) Keywords:Amorphous Crystallization Raman spectrometry Wide-angle X-ray scattering Xylitol Non-ordered mesoporous silica A B S T R A C TIn this paper we present a fast model system for monitoring the recrystallization of quench-cooled amorphous xylitol using Raman spectroscopy and wide-angle X-ray scattering. The use of these two methods enables comparison between surface and bulk crystallization. Non-ordered mesoporous silica micro-particles were added to the system in order to alter the rate of crystallization of the amorphous xylitol. Raman measurements showed that adding silica to the system increased the rate of surface crystallization, while X-ray measurements showed that the rate of bulk crystallization decreased. Using this model system it is possible to measure fast changes, which occur in minutes or within a few hours. Raman-spectroscopy and wide-angle X-ray scattering were found to be complementary techniques when assessing surface and bulk crystallization of amorphous xylitol.

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Section: Recrystallization Of Xylitol and Xylitol-silica Solid Dispermentioning

confidence: 54%

Section: Recrystallization Of Xylitol and Xylitol-silica Solid Dispermentioning

confidence: 93%

Section: Recrystallization Of Xylitol and Xylitol-silica Solid Dispermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Monitoring the recrystallisation of amorphous xylitol using Raman spectroscopy and wide-angle X-ray scattering

Palomäki

Ahvenainen

Ehlers

et al. 2016

International Journal of Pharmaceutics

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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 .…”

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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Physical Stability and Crystallization Inhibition

Taylor¹

2015

Pharmaceutical Sciences Encyclopedia

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In order to successfully utilize amorphous solid dispersions (ASDs) to enhance drug delivery, it is essential to maintain the amorphous form of the drug during the manufacturing process and the shelf life of the formulated product. It is essential to evaluate the crystallization tendency of the drug exposed to different environmental conditions and to develop strategies to modify crystallization kinetics through the addition of crystallization inhibitors. This chapter initially discusses crystallization in the solid state, including a consideration of the role of temperature, residual water, and additives. Subsequently, phase behavior during dissolution of an amorphous formulation is explored. The chapter presents an overview of the factors that need to be understood and controlled for successful formulation of an amorphous solid dispersion. It discusses different methods for physical stability assessment. Solid‐state nuclear magnetic resonance spectroscopy (SSNMR) is used to investigate a number of aspects of amorphous solid dispersions.

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Role of Thermodynamic, Molecular, and Kinetic Factors in Crystallization from the Amorphous State

Cited by 387 publications

References 85 publications

Monitoring the recrystallisation of amorphous xylitol using Raman spectroscopy and wide-angle X-ray scattering

Monitoring the recrystallisation of amorphous xylitol using Raman spectroscopy and wide-angle X-ray scattering

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

Physical Stability and Crystallization Inhibition

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