scholarly journals Physical stability of drugs after storage above and below the glass transition temperature: Relationship to glass-forming ability

2015 ◽  
Vol 495 (1) ◽  
pp. 312-317 ◽  
Author(s):  
Amjad Alhalaweh ◽  
Ahmad Alzghoul ◽  
Denny Mahlin ◽  
Christel A.S. Bergström
Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 425 ◽  
Author(s):  
Edueng ◽  
Bergström ◽  
Gråsjö ◽  
Mahlin

This study shows the importance of the chosen method for assessing the glass-forming ability (GFA) and glass stability (GS) of a drug compound. Traditionally, GFA and GS are established using in situ melt-quenching in a differential scanning calorimeter. In this study, we included 26 structurally diverse glass-forming drugs (i) to compare the GFA class when the model drugs were produced by spray-drying with that when melt-quenching was used, (ii) to investigate the long-term physical stability of the resulting amorphous solids, and (iii) to investigate the relationship between physicochemical properties and the GFA of spray-dried solids and their long-term physical stability. The spray-dried solids were exposed to dry (<5% RH) and humid (75% RH) conditions for six months at 25 °C. The crystallization of the spray-dried solids under these conditions was monitored using a combination of solid-state characterization techniques including differential scanning calorimetry, Raman spectroscopy, and powder X-ray diffraction. The GFA/GS class assignment for 85% of the model compounds was method-dependent, with significant differences between spray-drying and melt-quenching methods. The long-term physical stability under dry condition of the compounds was predictable from GFA/GS classification and glass transition and crystallization temperatures. However, the stability upon storage at 75% RH could not be predicted from the same data. There was no strong correlation between the physicochemical properties explored and the GFA class or long-term physical stability. However, there was a slight tendency for compounds with a relatively larger molecular weight, higher glass transition temperature, higher crystallization temperature, higher melting point and higher reduced glass transition temperature to have better GFA and better physical stability. In contrast, a high heat of fusion and entropy of fusion seemed to have a negative impact on the GFA and physical stability of our dataset.


2003 ◽  
Vol 18 (3) ◽  
pp. 664-671 ◽  
Author(s):  
Y. Zhang ◽  
H. Tan ◽  
H. Z. Kong ◽  
B. Yao ◽  
Y. Li

A eutectic point in Pr-rich Pr-(Cu,Ni)-Al alloys was experimentally determined by measuring the solidus temperature (Tm) and liquidus temperature (T1). It was found that Pr68(Cu0.5Ni0.5)25Al7 (at.%) is at the eutectic composition in the pseudoternary Pr–(Cu0.5Ni0.5)–Al alloys. The alloy Pr68(Cu0.5Ni0.5)25Al7 exhibits better glass-forming ability (GFA) than the ternary eutectic alloy Pr68Cu25Al7. However, the best GFA was obtained at an off-eutectic composition (Pr54[Cu0.5Ni0.5]30Al16) in the Pr–(Cu0.5Ni0.5)–Al alloys, which can be formed in fully amorphous rods with diameter of 1.5 mm by copper mold casting. Moreover, the glass-transition temperature Tg increases quickly (from 367 to 522 K) with the increasing of the Al content (from 3 to 27 at.%). The deviation of the best GFA composition from the eutectic point [Pr68(Cu0.5Ni0.5)25Al7] was explained in terms of the asymmetric coupled eutectic zone, the competition between growth of crystalline phase and formation of amorphous, and the higher glass-transition temperature Tg on the hypereutectic side.


2003 ◽  
Vol 18 (10) ◽  
pp. 2288-2291 ◽  
Author(s):  
H. Ma ◽  
E. Ma ◽  
J. Xu

We report a new Mg-based bulk metallic glass-forming alloy: Mg65Cu7.5Ni7.5Zn5 Ag5Y10. The alloy exhibits a glass-forming ability significantly stronger than all previously discovered Mg-based glass formers. Fully glassy rods 9 mm in diameter can be obtained by using copper mold casting. The critical cooling rate for glass formation was estimated to be <50 Ks−1. The reduced glass-transition temperature (Trg) of the glass was determined to be 0.59.


2011 ◽  
Vol 688 ◽  
pp. 426-430 ◽  
Author(s):  
Yan Fang Wang ◽  
Li Li ◽  
Chuan Sun ◽  
Qing Long Lu ◽  
Zhi Qiang Shi

The rare earth elements (RE= Y, Sm, La, Ce) were used as alloying materials in Cu50Zr45Al5BMG, and their influences on the glass-forming ability and thermal stability were studied in this paper. All the samples remained in full metallic glass state with minor additions of Y, Sm and La. Increasing the amount of RE additions, the Cu10Zr7and Zr2Cu phases precipitated and glass transition temperatureTgand crystallization temperatureTxsignificantly decreased. The reduced glass transition temperature Trg=Tg/Tlranged from 0.592 to 0.611 and the γ parameter ranged from 0.393 to 0.409.


2016 ◽  
Vol 18 (3) ◽  
pp. 1681-1692 ◽  
Author(s):  
Audrey Laventure ◽  
Guillaume De Grandpré ◽  
Armand Soldera ◽  
Olivier Lebel ◽  
Christian Pellerin

Mexylaminotriazine derivatives form molecular glasses with outstanding glass-forming ability (GFA), glass kinetic stability (GS), and tunable glass transition temperature. This work establishes key molecular parameters for efficient glass engineering.


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