Influence of Temperature on Solvent-Mediated Anhydrate-to-Hydrate Transformation Kinetics

Qu, Haiyan; Munk, Tommy; Cornett, Claus; Wu, Jian; Boetker, Johan; Christensen, Lars Porskjær; Rantanen, Jukka; Tian, Fang

doi:10.1007/s11095-010-0281-9

Cited by 25 publications

(26 citation statements)

References 21 publications

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“…It has been estimated that one third of active pharmaceutical substances are capable of forming a hydrate (16). In most cases, hydrates contain water molecules within the crystal lattice that are bound at either isolated or channel sites (17).…”

Section: Discussionmentioning

confidence: 99%

Solid-State and Solution Characterization of Myricetin

Franklin

Myrdal

2015

AAPS PharmSciTech

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Abstract. Myricetin (MYR) is a natural compound that has been investigated as a chemopreventative agent. MYR has been shown to suppresses ultraviolet B (UVB)-induced cyclooxygenase-2 (COX-2) protein expression and reduce the incidence of UVB-induced skin tumors in mice. Despite MYR's promise as a therapeutic agent, minimal information is available to guide the progression of formulations designed for future drug development. Here, data is presented describing the solid-state and solution characterization of MYR. Investigation into the solid-state properties of MYR identified four different crystal forms, two hydrates (MYR I and MYR II) and two metastable forms (MYR IA and MYR IIA). From solubility studies, it was evident that all forms are very insoluble (<5 μg/ml) in pure water. MYR I was found to be the most stable form at 23, 35, and 56°C. Stability determination indicated that MYR undergoes rapid apparent first-order degradation under basic pH conditions, and that degradation was influenced by buffer species. Apparent first-order degradation was also seen when MYR was introduced to an oxidizing solution. Improved stability was achieved after introducing 0.1% antioxidants to the solution. MYR was found to have good stability following exposure to ultraviolet radiation (UVR), which is a consideration for topical applications. Finally, a partitioning study indicated that MYR possess a log P of 2.94 which, along with its solid-state properties, contributes to its poor aqueous solubility. Both the solid-state properties and solution stability of MYR are important to consider when developing future formulations.

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Section: Discussionmentioning

confidence: 99%

Solid-State and Solution Characterization of Myricetin

Franklin

Myrdal

2015

AAPS PharmSciTech

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“…Thermodynamic factors illustrate parameters that impact or control the driving force for the polymorphic transformation, namely, the polymorphs’ supersaturation [10,11,12]. This includes temperature, type of solvent, solvent composition, and so on [6,9,13,14,15,16,17,18]. Moreover, factors such as solvent viscosity, rotational speed, concentration of suspension, additive or seed addition, particle size, and so on dynamically affect the polymorphic transformation and physically impact the rate of polymorphic transformation [18,19,20,21].…”

Section: Introductionmentioning

confidence: 99%

Kinetics of the Solution-Mediated Polymorphic Transformation of the Novel l-Carnitine Orotate Polymorph, Form-II

Youn

Kiyonga

et al. 2018

Pharmaceutics

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Research studies related to the polymorphs of l-Carnitine orotate (CO), a medication used for the treatment and prevention of liver diseases, are insignificant or almost nonexistent. Accordingly, in the present study, l-Carnitine orotate (CO) was prepared for investigating CO polymorphs. Here, a reactive crystallization was induced by reacting 1g of l-Carn (1 equivalent) and 0.97 g of OA (1 equivalent) in methanol (MeOH); as a result, CO form-I and CO form-II polymorphs were obtained after 1 h and 16 h of stirring, respectively. The characterization of CO polymorphs was carried out utilizing Powder X-ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA) and solid-state Nuclear Magnetic Resonance Spectroscopy (solid-state CP/MAS 13C-NMR). The solution-mediated polymorphic transformation (SMPT) of CO polymorphs was investigated in MeOH at controlled temperature and fixed rotational speed. The results revealed that CO form-I is a metastable polymorph while CO form-II is a stable polymorph. From the same results, it was confirmed that CO form-I was converted to CO form-II during the polymorphic phase transformation process. Moreover, it was assessed that the increase in temperature and supersaturation level significantly promotes the rate of nucleation, as well as the rate of mass transfer of CO form-II. In addition, nucleation and mass transfer equations were employed for the quantitative determination of SMPT experimental results. Lastly, it was suggested that CO form-II was more thermodynamically stable than CO form-I and that both polymorphs belong to the monotropic system.

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“…An estimated one-third of active pharmaceutical substances are capable of forming a hydrate. 27 The addition of the water molecule(s) in the crystal lattice alters the physical structure and properties of the drug substance including changes to the dimensions, shape, symmetry, and the unit cell. 28 These changes lead to differences in pharmaceutical properties such as solubility and chemical stability.…”

Section: Introductionmentioning

confidence: 99%

Estimating the Aqueous Solubility of Pharmaceutical Hydrates

Franklin

Younis

Myrdal

2016

Journal of Pharmaceutical Sciences

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Estimation of crystalline solute solubility is well documented throughout the literature. However, the anhydrous crystal form is typically considered with these models, which is not always the most stable crystal form in water. In this study an equation which predicts the aqueous solubility of a hydrate is presented. This research attempts to extend the utility of the ideal solubility equation by incorporating desolvation energetics of the hydrated crystal. Similar to the ideal solubility equation, which accounts for the energetics of melting, this model approximates the energy of dehydration to the entropy of vaporization for water. Aqueous solubilities, dehydration and melting temperatures, and log P values were collected experimentally and from the literature. The data set includes different hydrate types and a range of log P values. Three models are evaluated, the most accurate model approximates the entropy of dehydration (ΔSd) by the entropy of vaporization (ΔSvap) for water, and utilizes onset dehydration and melting temperatures in combination with log P. With this model, the average absolute error for the prediction of solubility of 14 compounds was 0.32 log units.

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Influence of Temperature on Solvent-Mediated Anhydrate-to-Hydrate Transformation Kinetics

Abstract: By differentiating and comparing the effects of temperature and supersaturation on the anhydrate-to-hydrate phase transformation, a deeper understanding of the underlying principle of the acceleration and deceleration effects of temperature on the phase transformation has been achieved.

Cited by 25 publications

References 21 publications

Solid-State and Solution Characterization of Myricetin

Solid-State and Solution Characterization of Myricetin

Kinetics of the Solution-Mediated Polymorphic Transformation of the Novel l-Carnitine Orotate Polymorph, Form-II

Estimating the Aqueous Solubility of Pharmaceutical Hydrates

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