Crystallization kinetics and glass-forming ability of rapidly crystallizing drugs studied by Fast Scanning Calorimetry

The use of the amorphous forms of drugs is a modern approach for the enhancement of bioavailability. At the same time, the high cooling rate needed to obtain the metastable amorphous state often prevents its investigation using conventional laboratory methods such as differential scanning calorimetry, X-ray powder diffractometry. One of the ways to overcome this problem may be the application of Fast Scanning Calorimetry. This method allows direct determination of the critical cooling rate of the melt and kinetic parameters of the crystallization for bad glass formers. In the present work, the amorphous states of dopamine hydrochloride and atenolol were created using Fast Scanning Calorimetry for the first time. Critical cooling rates and glass transition temperatures of these drugs were determined. Based on the values of the kinetic fragility parameter, dopamine hydrochloride glass can be considered strong, while atenolol glass is moderately strong. Both model-based and model-free approaches were employed to determine the kinetic parameters of cold crystallization of dopamine and atenolol. The results were compared with the data from isothermal crystallization experiments. The Nakamura crystallization model provides the best description of the crystallization process and can be used to predict the long term stability of the amorphous forms of the drugs. The presented approaches may find applications in predicting the storage time and choosing the optimal storage conditions of the amorphous drugs prone to crystallization

Kinetic stability of amorphous dipyridamole: A fast scanning calorimetry investigation

© 2019 Elsevier B.V. One of the main tasks of modern pharmaceutics is enhancing the solubility of drugs. The approaches for solving this problem include producing active pharmaceutical ingredients in the amorphous state. However, the use of amorphous drugs requires the determination of their kinetic stability. The latter is often assessed using isothermal techniques, which are time-consuming. Alternatively, non-isothermal methods can be employed, allowing to determine the kinetic triplet more rapidly. Also, such techniques can be used to develop predictive models for storage stability. The production of the amorphous state itself typically requires fast cooling rates, which may not be easily accessible. Fast scanning calorimetry is a promising tool for the investigation of amorphous drug systems. In the present work, the crystallization of the model drug dipyridamole was investigated using the fast scanning calorimetry method. The kinetic stability of the amorphous form of the drug was evaluated using both, isothermal and non-isothermal methods. The Nakamura crystallization model was found to be applicable for the prediction of the temporal stability of the amorphous drug forms. The obtained results may find applications in the investigation of the kinetic stability of amorphous drug systems

Hexamorphism of Dantrolene: Insight into the Crystal Structures, Stability, and Phase Transformations

Dantrolene represents yet another interesting example of abundant molecular crystal polymorphism existing in at least six different neat polymorphs, three of which can be obtained via crystallization (I-III) and an additional three (IV- VI) via solid-state dehydration from three different monohydrates (MH-I-MH-III). The reasons for polymorph formation were rationalized by analyzing the crystal structures of the polymorphs and hydrates used in their preparation. The thermodynamic relations among the polymorphs were established from calorimetric data, solubility measurements, and lattice energy calculations

A thermal study on peat oxidation behavior in the presence of an iron-based catalyst

Peat is a resource used for heat and energy, particularly in countries where peat is abundant and conventional fuels are not available. Some countries have made extensive use of peat resources to produce electricity and heat in addition to light hydrocarbons. By doing so, they were able to reduce the cost of importing fossil fuels. To the best of our knowledge, there is a lack of a detailed description of the peat oxidation process in the presence of other substances. Herein, the process of peat oxidation was studied in-depth by means of thermal analysis in the presence of iron tallate acting as a catalytic agent. Differential scanning calorimetry and thermogravimetric analysis demonstrated an oil-like oxidation behavior during the combustion of the used peat. The process of peat oxidation includes two main regions: low-temperature oxidation (LTO), which occurs during the oxidation of light hydrocarbons, followed by the so-called high-temperature oxidation (HTO), which includes the oxidation of the obtained coke-like product. Moreover, the application of non-isothermal kinetics experiments based on the isoconversional and model approach principle have confirmed the role of 2% iron tallate in peat mass by improving the oxidation rate at low-and high-temperature oxidation (HTO) regions. The results obtained from this study have proven that the added catalyst improves efficiency with regards to the energy activation in the process by leading to its significant decrease from 110.8 ± 7.8 kJ/mol to 81.8 ± 7.5 kJ/mol for LTO and from 157.8 ± 19.1 kJ/mol to 137.6 ± 9.3 kJ/mol for HTO. These findings clearly confirm the improvement in the rate of the process by shifting the LTO and HTO peaks to lower regions in the presence of the catalyst. These results further emphasize the possible impact which could be generated by the application of thermally enhanced oil recovery methods on peat development and exploitation

Effect of Ligand Structure on the Kinetics of Heavy Oil Oxidation: Toward Biobased Oil-Soluble Catalytic Systems for Enhanced Oil Recovery

In recent years, protection of the environment from activities associated with enhanced oil recovery has been considered a crucial priority for decision-makers in the international community. The in situ combustion process as a promising thermal enhanced oil recovery method has been attracting considerable interest in terms of improving oil production and environmental protection. However, this technique is not yet well studied. This paper outlines a new approach to improve the process of heavy oil oxidation by designing new biobased oil-soluble catalysts that are able to maintain and stabilize the combustion flame front of the in situ combustion process. A comprehensive theoretical and experimental study including thermal analysis (thermogravimetry/differential scanning calorimetry, TG/DSC) and quantum calculations was used to shed light on the effect of the ligand structure in the oil-soluble catalytic system on the heavy oil oxidation process. The obtained accurate results proved that metal interaction with the designed ligands increased, which led to a decrease in the energy of activation and an increase in the heavy oil oxidation reaction rate. Besides, the obtained DSC curves showed one peak in the presence of Cu and biobased ligands, contrary to the curves obtained for heavy oil oxidation reported with other ligands and metals. In other words, the obtained catalysts merged low-temperature- and high-temperature oxidation regions into one region. These findings reveal that the structure of ligands can significantly affect their interaction with metals in oil-soluble catalysts, and therefore the efficiency of catalysts is dramatically improved. We believe that our work could be usefully employed for further studies to clarify the mechanism of the in situ combustion behavior of heavy oil for a better impact on the environment