An investigation into the crystallization tendency/kinetics of amorphous active pharmaceutical ingredients: A case study with dipyridamole and cinnarizine

Baghel, Shrawan; Cathcart, Helen; Redington, Wynette; O’Reilly, Niall J.

doi:10.1016/j.ejpb.2016.04.017

Cited by 40 publications

(38 citation statements)

References 69 publications

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“…The thermal properties were used in the calculation of the free energy difference between amorphous and crystal forms of indomethacin, which in combination with other measurements provided information for the theoretical prediction of solubility. Baghel et al [86] studied the tendency and kinetics of crystallization of two amorphous active pharmaceutical systems, dipyridamole (DPM) and cinnarizine (CNZ). MDSC was employed for obtaining the heat capacity changes at the glass transition temperature in order to get the thermodynamic fragility (mT) of both systems.…”

Section: Pharmaceutical Productsmentioning

confidence: 99%

Application of Differential Scanning Calorimetry (DSC) and Modulated Differential Scanning Calorimetry (MDSC) in Food and Drug Industries

et al. 2019

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Phase transition issues in the field of foods and drugs have significantly influenced these industries and consequently attracted the attention of scientists and engineers. The study of thermodynamic parameters such as the glass transition temperature (Tg), melting temperature (Tm), crystallization temperature (Tc), enthalpy (H), and heat capacity (Cp) may provide important information that can be used in the development of new products and improvement of those already in the market. The techniques most commonly employed for characterizing phase transitions are thermogravimetric analysis (TGA), dynamic mechanical analysis (DMA), thermomechanical analysis (TMA), and differential scanning calorimetry (DSC). Among these techniques, DSC is preferred because it allows the detection of transitions in a wide range of temperatures (−90 to 550 °C) and ease in the quantitative and qualitative analysis of the transitions. However, the standard DSC still presents some limitations that may reduce the accuracy and precision of measurements. The modulated differential scanning calorimetry (MDSC) has overcome some of these issues by employing sinusoidally modulated heating rates, which are used to determine the heat capacity. Another variant of the MDSC is the supercooling MDSC (SMDSC). SMDSC allows the detection of more complex thermal events such as solid–solid (Ts-s) transitions, liquid–liquid (Tl-l) transitions, and vitrification and devitrification temperatures (Tv and Tdv, respectively), which are typically found at the supercooling temperatures (Tco). The main advantage of MDSC relies on the accurate detection of complex transitions and the possibility of distinguishing reversible events (dependent on the heat capacity) from non-reversible events (dependent on kinetics).

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Section: Pharmaceutical Productsmentioning

confidence: 99%

Application of Differential Scanning Calorimetry (DSC) and Modulated Differential Scanning Calorimetry (MDSC) in Food and Drug Industries

et al. 2019

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“…It is well established that compounds with high molecular weight are difficult to crystallize compared to systems with low molecular weight (Baird et al, 2010). Moreover, the propensity to form a glass can be affected by the number of aromatic rings, number of electronegative atoms, presence of flexible and rotating branches, intermolecular and intramolecular connections (Baghel et al, 2016;Kawakami et al, 2015;Miyazaki et al, 2007). Furthermore, it was observed that liquids composed of symmetric molecules crystallize more easily than liquids made of asymmetric molecules.…”

Section: High Crystallization Propensity Of 12hmentioning

confidence: 99%

Impact of chirality on the Glass Forming Ability and the crystallization from the amorphous state of 5-ethyl-5-methylhydantoin, a chiral poor glass former

Atawa

Couvrat

Coquerel

et al. 2018

International Journal of Pharmaceutics

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The investigation of the glassy state of 5-ethyl-5-methylhydantoin (i.e. 12H, a chiral Active Pharmaceutical Ingredient) was attempted by Differential Scanning Calorimetry (DSC) and Fast Scanning Calorimetry (FSC). This compound exhibits a high crystallization propensity for every enantiomeric composition. Nevertheless, glassy states of pure enantiomer or mixtures between enantiomers were successfully reached by FSC at cooling rates of: 1000 °C/s and 300 °C/s respectively, even though limitations on the sampling reproducibility were evidenced due to FSC sample size. The Glass Forming Ability (GFA) was proven to increase with the counter-enantiomer content. From the glassy state, pure enantiomer displayed a more pronounced crystallogenic character (with a crystallization occurring 36 °C below Tg during ageing) than that of the mixture between enantiomers. Ageing of amorphous 12H promotes a strong nucleation behavior in both samples but enantiopure 12H crystallizes upon ageing while scalemic 12H evolves towards the metastable equilibrium. Finally, potential new phase equilibria (previously not reported) in the enantiomeric phase diagram could have been highlighted by FSC by recrystallization from the amorphous state.

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“…These drugs also have problems such as non-constant absorption in vivo and low bioavailability (BA) [2]. Approaches to improve solubility and absorption include drug miniaturization [3,4,5], amorphization [6,7,8], and solid dispersion [9,10,11]. In particular, nanoparticle formulations have been useful in drug delivery [12].…”

Section: Introductionmentioning

confidence: 99%

Combination of Roll Grinding and High-Pressure Homogenization Can Prepare Stable Bicelles for Drug Delivery

et al. 2018

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To improve the solubility of the drug nifedipine (NI), NI-encapsulated lipid-based nanoparticles (NI-LNs) have been prepared from neutral hydrogenated soybean phosphatidylcholine and negatively charged dipalmitoylphosphatidylglycerol at a molar ratio of 5/1 using by roll grinding and high-pressure homogenization. The NI-LNs exhibited high entrapment efficiency, long-term stability, and enhanced NI bioavailability. To better understand their structures, cryo transmission electron microscopy and atomic force microscopy were performed in the present study. Imaging from both instruments revealed that the NI-LNs were bicelles. Structures prepared with a different drug (phenytoin) or with phospholipids (dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, and distearoylphosphatidylcholine) were also bicelles. Long-term storage, freeze-drying, and high-pressure homogenization did not affect the structures; however, different lipid ratios, or the presence of cholesterol, did result in liposomes (5/0) or micelles (0/5) with different physicochemical properties and stabilities. Considering the result of long-term stability, standard NI-LN bicelles (5/1) showed the most long-term stabilities, providing a useful preparation method for stable bicelles for drug delivery.

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An investigation into the crystallization tendency/kinetics of amorphous active pharmaceutical ingredients: A case study with dipyridamole and cinnarizine

Cited by 40 publications

References 69 publications

Application of Differential Scanning Calorimetry (DSC) and Modulated Differential Scanning Calorimetry (MDSC) in Food and Drug Industries

Application of Differential Scanning Calorimetry (DSC) and Modulated Differential Scanning Calorimetry (MDSC) in Food and Drug Industries

Impact of chirality on the Glass Forming Ability and the crystallization from the amorphous state of 5-ethyl-5-methylhydantoin, a chiral poor glass former

Combination of Roll Grinding and High-Pressure Homogenization Can Prepare Stable Bicelles for Drug Delivery

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