Crystallization of Organic Glasses: Effects of Polymer Additives on Bulk and Surface Crystal Growth in Amorphous Nifedipine

Cai, Ting; Zhu, Lei; Yu, Lian

doi:10.1007/s11095-011-0472-z

Cited by 76 publications

(131 citation statements)

References 46 publications

(56 reference statements)

Supporting

Mentioning

120

Contrasting

Order By: Relevance

“…This inhibitory effect is remarkable and suggests that lowconcentration polymer additives can substantially stabilize amorphous drugs against crystallization. Their finding was substantiated by Cai et al (69), who showed that the logarithm of the bulk crystal growth rate decreases linearly with the concentration of PVP in weight percent (Fig. 7).…”

Section: Polymer Additives Can Have Different Effects On Bulk and Surmentioning

confidence: 59%

“…Although PVP additives can strongly inhibit bulk crystal growth in NIF glasses, their effect on surface crystal growth is much weaker (69). Figure 7 shows that both log u s and log u b decrease linearly with increasing concentration of PVP K15 in weight percent, log u b decreases approximately three times faster than log u s .…”

Section: Polymer Additives Can Have Different Effects On Bulk and Surmentioning

confidence: 99%

“…Amorphous calcium carbonate, though crystallizing readily if chemically pure, exists in many organisms (63), and can be stabilized by dendrimers (64) and proteins (65,66). In pharmaceutical science, polymers are known to inhibit the crystallization of amorphous drugs (24,(67)(68)(69). Aso et al observed that the presence of 10% PVP slows the rate of total crystallization of amorphous NIF by a factor of 300 (67).…”

Section: Polymer Inhibitors Of Crystallization Of Amorphous Solidsmentioning

confidence: 99%

“…Aso et al observed that the presence of 10% PVP slows the rate of total crystallization of amorphous NIF by a factor of 300 (67). Although amorphous pharmaceutical formulations may contain polymers as the major component, recent studies have examined the use of low-concentration polymers as crystallization inhibitors (24,68,69). Such studies are a necessary first step for understanding more complex formulations, and could discover effective polymer additives that significantly improve the properties of amorphous drugs.…”

Section: Polymer Inhibitors Of Crystallization Of Amorphous Solidsmentioning

confidence: 99%

“…Cai et al (69) considered several explanations for the weaker inhibition of surface crystal growth by polymer additives than bulk crystal growth: (1) lower polymer concentration at the surface than in the bulk; (2) upward growth of surface crystals making the process less sensitive to polymer impurities; and (3) surface molecular mobility making polymers less effective as crystal growth inhibitors. Further work is needed to determine which explanation accurately accounts for the effect observed.…”

Section: Polymer Additives Can Have Different Effects On Bulk and Surmentioning

confidence: 99%

See 4 more Smart Citations

Stability of Amorphous Pharmaceutical Solids: Crystal Growth Mechanisms and Effect of Polymer Additives

Sun

Zhu

et al. 2012

AAPS J

Self Cite

136

View full text Add to dashboard Cite

Abstract. We review recent progress toward understanding and enhancing the stability of amorphous pharmaceutical solids against crystallization. As organic liquids are cooled to become glasses, fast modes of crystal growth can emerge. One such growth mode, the glass-to-crystal or GC mode, occurs in the bulk, and another exists at the free surface, both leading to crystal growth much faster than predicted by theories that assume diffusion defines the kinetic barrier of crystallization. These phenomena have received different explanations, and we propose that GC growth is a solid-state transformation enabled by local mobility in glasses and that fast surface crystal growth is facilitated by surface molecular mobility. In the second part, we review recent findings concerning the effect of polymer additives on crystallization in organic glasses. Low-concentration polymer additives can strongly inhibit crystal growth in the bulk of organic glasses, while having weaker effect on surface crystal growth. Ultra-thin polymer coatings can inhibit surface crystallization. Recent work has shown the importance of molecular weight for crystallization inhibitors of organic glasses, besides "direct intermolecular interactions" such as hydrogen bonding. Relative to polyvinylpyrrolidone, the VP dimer is far less effective in inhibiting crystal growth in amorphous nifedipine. Further work is suggested for better understanding of crystallization of amorphous organic solids and the prediction of their stability.

show abstract

Section: Polymer Additives Can Have Different Effects On Bulk and Surmentioning

confidence: 59%

Section: Polymer Additives Can Have Different Effects On Bulk and Surmentioning

confidence: 99%

Section: Polymer Inhibitors Of Crystallization Of Amorphous Solidsmentioning

confidence: 99%

Section: Polymer Inhibitors Of Crystallization Of Amorphous Solidsmentioning

confidence: 99%

Section: Polymer Additives Can Have Different Effects On Bulk and Surmentioning

confidence: 99%

See 3 more Smart Citations

Stability of Amorphous Pharmaceutical Solids: Crystal Growth Mechanisms and Effect of Polymer Additives

Sun

Zhu

et al. 2012

AAPS J

Self Cite

136

View full text Add to dashboard Cite

show abstract

Introduction to Amorphous Solid Dispersions

Zografi¹,

Newman²

2015

Pharmaceutical Sciences Encyclopedia

View full text Add to dashboard Cite

This chapter reviews some of the important physicochemical characteristics of amorphous solids as single components and as mixtures of active pharmaceutical ingredient (API) with other formulation components that might be used to enhance oral bioavailability in drug products. The structural arrangement of molecules in crystals, as determined by intermolecular interactions and molecular size and shape, can be described in terms of a specific local structure reflected by the geometric arrangement of molecules within the unit cell, and the long‐range symmetrical three‐dimensional extension of the repeating unit cells. From a thermodynamic perspective molecules in the amorphous state are in a higher free energy state than those in the corresponding crystal at all temperatures. In the case of amorphous solid dispersions, a miscible amorphous system is generally required to obtain appropriate levels of stability, enhanced dissolution, and oral absorption.

show abstract

Poly(alkylimidazolium bis(trifluoromethylsulfonyl)imide)‐Based Polymerized Ionic Liquids: A Potential High‐Performance Lubricating Grease

Feng

et al. 2019

Adv Materials Inter

View full text Add to dashboard Cite

Polymers prepared from ionic liquids are widely called polymerized ionic liquids (PILs). Compared to monocationic and dicationic ILs, PILs have higher molecular weights, charge, and greater intermolecular interactions, which make PILs have a higher possibility to generate better lubricity. PILs of poly‐alkylimidazolium bis(trifluoromethylsulfonyl)imide (PImC6NTf2) is studied herein. Dicationic ILs of 1,1′‐(pentane‐1,5‐diyl)‐bis(3‐butylimidazolium) bis(trifluoromethylsulfonyl)imide (BIm5‐(NTf2)2) is used as additive to decrease the crystallization temperature of PImC6NTf2. Lubricity of PImC6NTf2 and PImC6NTf2+BIm5‐(NTf2)2, as well as BIm5‐(NTf2)2 for comparison is evaluated under severe conditions, i.e., 3.0 to 3.5 GPa and 200 °C. The rheological study suggests that PImC6NTf2 can be classified into grease. Tribological test results show that PImC6NTf2 has much better antiwear property than BIm5‐(NTf2)2, especially at 3.5 GPa. Adding 4% BIm5‐(NTf2)2 to PImC6NTf2 is able to reduce friction under high pressure. At 200 °C, PImC6NTf2 exhibits excellent lubricity. The mixture of 96%PImC6NTf2+4%BIm5‐(NTf2)2 shows even better antiwear property than neat PImC6NTf2 and exhibits the highest friction reducing property among the ILs at 200 °C. It is speculated that the robust strength of PILs and strong adhesion between PILs and solids are key factors in achieving the excellent antiwear property.

show abstract

Crystallization of Organic Glasses: Effects of Polymer Additives on Bulk and Surface Crystal Growth in Amorphous Nifedipine

Abstract: Polymer additives inhibit crystal growth in nifedipine glasses more strongly in the bulk than at the surface. The effectiveness of crystallization inhibitors depends not only on intermolecular interactions but also on molecular sizes.

Cited by 76 publications

References 46 publications

Stability of Amorphous Pharmaceutical Solids: Crystal Growth Mechanisms and Effect of Polymer Additives

Stability of Amorphous Pharmaceutical Solids: Crystal Growth Mechanisms and Effect of Polymer Additives

Introduction to Amorphous Solid Dispersions

Poly(alkylimidazolium bis(trifluoromethylsulfonyl)imide)‐Based Polymerized Ionic Liquids: A Potential High‐Performance Lubricating Grease

Contact Info

Product

Resources

About