Rapid Insight into Heating-Induced Phase Transformations in the Solid State of the Calcium Salt of Atorvastatin Using Multivariate Data Analysis

Christensen, Niels Peter Aae; Eerdenbrugh, Bernard Van; Kwok, Kaho; Taylor, Lynne S.; Bond, Andrew D.; Rades, Thomas; Cornett, Claus

doi:10.1007/s11095-012-0923-1

Cited by 19 publications

(14 citation statements)

References 28 publications

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“…Likewise, the shifts in the region of 1300-1350 cm −1 carry characteristics of both forms III and II. Further elucidation of these phenomena could potentially be performed with faster off-line methods, such as synchrotron-based diffraction studies [24].…”

Section: Solid Forms Detected In the Molten Polymer Mixturesmentioning

confidence: 99%

“…MCR offers an estimation of pure analyte signals and can thus provide quantification of the individual components in complex mixtures and their individual compound spectra, even in situations with limited prior information [21,23]. MCR has previously been applied to variable temperature diffraction data for exploration of the solid forms appearing during the dehydration of an atorvastatin calcium salt hydrate, and the kinetics of this transformation [24], where it was found that MCR provided a reliable tool for quick qualitative and quantitative assessment of phase transformations studied by X-ray powder diffraction.…”

Section: Introductionmentioning

confidence: 99%

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Exploring the Complexity of Processing-Induced Dehydration during Hot Melt Extrusion Using In-Line Raman Spectroscopy

et al. 2020

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The specific aim in this study was to understand the effect of critical process parameters on the solid form composition of model drug compounds during hot melt extrusion using in-line Raman spectroscopy combined with Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) modeling for semi-quantitative kinetic profiling. It was observed that the hydrate and anhydrate solid forms of two model drugs in the melts of nitrofurantoin (NF):polyethylene oxide (PEO) and piroxicam (PRX):PEO could be resolved from a MCR-ALS model without an external calibration dataset. Based on this model, the influence of two critical process parameters (shear and temperature) on the solid form composition could be evaluated in a real-time mode and the kinetics of complex transformation pathways could be explored. Additionally, the dehydration pathways of NF monohydrate and PRX monohydrate in molten PEO could be derived. It can be concluded that dehydration of both hydrates in PEO occurs via competing mechanisms—a solution-mediated transformation pathway and a solid–solid transformation, and that the balance between these mechanisms is determined by the combined effect of both temperature and shear. Another important observation was that the water released from these hydrate compounds has a detectable effect on the rheological characteristics of this mixture.

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Section: Solid Forms Detected In the Molten Polymer Mixturesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exploring the Complexity of Processing-Induced Dehydration during Hot Melt Extrusion Using In-Line Raman Spectroscopy

et al. 2020

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“…Deciding which of the two types of phase diagrams reflects the behavior of the trihydrate of atorvastatin calcium involves measuring the phase behavior as a function of the temperature for different compositions. A major problem for the trihydrate system of atorvastatin calcium is that many of the calorimetric phenomena occur above 100°C (Christensen et al, 2013), which implies that water evaporation and the vapor phase need to be considered too. Solubility is part of the phase diagram in Figure 2, because this is the equilibrium value of the maximum concentration of solid phase that dissolves in the liquid phase and it represents therefore a point on the liquidus line around room temperature.…”

Section: Referencesmentioning

confidence: 99%

“…Using temperature dependent X-ray diffraction and multivariate analysis, they clearly show the relative presence of the trihydrate, dihydrate, and monohydrate as a function of the temperature. Once the water has left, the structure turns into a liquid crystal, a mesophase, which becomes an isotropic liquid at around 155 °C according to the multivariate analysis of the powder X-ray diffraction results (Christensen et al, 2013).…”

Section: Referencesmentioning

confidence: 99%

“…is another question that could come to mind. Part of the answer can be found in the paper by Christensen et al describing the dehydration of ATC 3H 2 O among other methods through X-ray diffraction as a function of temperature and multivariate analysis (Christensen et al, 2013). The answer for most experimental setups boils down to "there is no melting solid" and the present paper will demonstrate this in terms of a binary phase diagram with the pure components defined as H 2 O and ATC (atorvastatin calcium without any water).…”

Section: Referencesmentioning

confidence: 99%

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Does the trihydrate of atorvastatin calcium possess a melting point?

Tizaoui

Galai²,

Clevers

et al. 2020

European Journal of Pharmaceutical Sciences

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To decide whether an active pharmaceutical ingredient can be used in its amorphous form in drug formulations, often the glass transition is studied in relation to the melting point of the pharmaceutical. If the glass transition temperature is high enough and found relatively close to the melting point, the pharmaceutical is considered to be a good glass former. However, it is obviously important that the observed melting point and glass transition involve exactly the same system, otherwise the two temperatures cannot be compared. Although this may seem trivial, in the case of hydrates, where water may leave the system on heating, the composition of the system may not be evident. Atorvastatin calcium is a case in point, where confusing terminology, absence of a proper anhydrate form, and loss of water on heating lead to several doubtful conclusions in the literature. However, considering that no anhydrate crystal has ever been observed and that the glass transition of the anhydrous system is found at 144 °C, it can be concluded that if the system is kept isolated from water, the chances that atorvastatin calcium crystallises at room temperature is negligible. The paper discusses the various thermal effects of atorvastatin calcium on heating and proposes a tentative binary phase diagram with water.

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Constant rate thermal analysis study of a trihydrate calcium atorvastatin and effect of grinding on its thermal stability

Meddeb,

Elmhamdi,

Aksit

et al. 2023

J Therm Anal Calorim

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Rapid Insight into Heating-Induced Phase Transformations in the Solid State of the Calcium Salt of Atorvastatin Using Multivariate Data Analysis

Abstract: This study demonstrates that MCR combined with VT-XRPD is a powerful tool for rapid interpretation of complex dehydration behavior of drug hydrates, and it is also the first report on a liquid crystalline phase of the calcium salt of atorvastatin.

Cited by 19 publications

References 28 publications

Exploring the Complexity of Processing-Induced Dehydration during Hot Melt Extrusion Using In-Line Raman Spectroscopy

Exploring the Complexity of Processing-Induced Dehydration during Hot Melt Extrusion Using In-Line Raman Spectroscopy

Does the trihydrate of atorvastatin calcium possess a melting point?

Constant rate thermal analysis study of a trihydrate calcium atorvastatin and effect of grinding on its thermal stability

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