Conformational Polymorphism of Tolbutamide: A Structural, Spectroscopic, and Thermodynamic Characterization of Burger’s Forms I–IV

Thirunahari, Satyanarayana; Aitipamula, Srinivasulu; Tan, Reginald B. H.

doi:10.1002/jps.22061

Cited by 67 publications

(86 citation statements)

References 41 publications

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“…The FII curve shown in Figure 2 has a small peak at 311 K, corresponding to the faint endotherm observed on heating FII, Figure 1 The calorimetric data appears to support the reported observation [7] with regard to the stability relationship of FI L and FI H . In the DSC pan, the transformation between FI L and FI H repeatedly and kinetically reversibly occurred at 311 K. This results in the complete inaccessibility of FI H below this temperature and of FI L above it.…”

Section: Thermodynamic Stability Relationship Of Tolbutamide Polymorphssupporting

confidence: 79%

“…[7] The Gibbs energy estimates of FI H and FII become equal at a temperature of 333 K. This value is somewhat below the estimate of Thirunahari et al [7] of 353 K, which is based on a simplified extrapolation of solubility data in methanol. However, it should be noted that there is also a significant uncertainty associated with our estimated value, mainly resulting from the closeness of the two Gibbs energy isobars, but also from the lack of calorimetric data on the fusion of FII.…”

Section: Thermodynamic Stability Relationship Of Tolbutamide Polymorphsmentioning

confidence: 74%

“…However, the consistently observed FII→FI H transformation precluded observation of a melting peak of FII. Thirunahari et al [7] were able to observe the onset of melting prior to polymorphic transformation, and report the melting point to be 390 K. An estimate of the enthalpy of fusion of FII at this temperature was obtained from the enthalpy of the transition FII → FI H , the enthalpy of fusion of FI H at Tm,FIH and integrated heat capacities (using Eq. 2 and coefficients in Table 2) according to the thermodynamic cycle 1-7 outlined in Figure 3.…”

Section: Thermodynamic Stability Relationship Of Tolbutamide Polymorphsmentioning

confidence: 99%

“…[7,8] At ambient conditions FII is reported to be the stable solid form, followed by FI L and then the more metastable forms FIII and FIV. [7] FV is reported to be 1D-isostructural with FIV and to rapidly convert into FI L at ambient conditions. [8] On heating the pure solid, at approx.…”

Section: Introductionmentioning

confidence: 99%

“…[7] The structural similarity of FI L and FI H , and the reported kinetic reversibility of the interconversion, are the reasons for the peculiar naming of these two polymorphs. At higher temperatures FI H is the stable polymorph with a high melting point of 401 K. [7] The thermodynamic transition temperature between FII and FI H is verified to be below 390 K (the reported melting point of FII) and, based on a comparison of solubility data in ethanol, should be located near 353 K. [7] In this work, we report the solubility of the low-temperature stable polymorph FII between 278 K and 313 K in 5 pure organic solvents: methanol, 1-propanol, ethyl acetate, acetonitrile and toluene. Based on a comprehensive thermodynamic analysis of calorimetric data, the Gibbs energy, enthalpy and entropy of fusion are calculated as functions of temperature for polymorphs FI L , FI H , FII and FV, allowing a more comprehensive and accurate establishment of the stability relationship than previously reported.…”

Section: Introductionmentioning

confidence: 99%

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Thermodynamic Stability Analysis of Tolbutamide Polymorphs and Solubility in Organic Solvents

Svärd

Valavi

Khamar

et al. 2016

Journal of Pharmaceutical Sciences

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Melting temperatures and enthalpies of fusion have been determined by differential scanning calorimetry (DSC) for two polymorphs of the drug tolbutamide: FI H and FV. Heat capacities have been determined by temperature-modulated DSC for four polymorphs: FI L , FI H , FII, FV, and for the supercooled melt. The enthalpy of fusion of FII at its melting point has been estimated from the enthalpy of transition of FII into FI H through a thermodynamic cycle. Calorimetric data has been used to derive a quantitative polymorphic stability relationship between these four polymorphs, showing that FII is the stable polymorph below approx. 333 K, above which temperature FI H is the stable form up to its melting point. The relative stability of FV is well below the other polymorphs. The previously reported kinetic reversibility of the transformation between FI L and FI H has been verified using in situ Raman spectroscopy. The solid-liquid solubility of FII has been gravimetrically determined in five pure organic solvents (methanol, 1-propanol, ethyl acetate, acetonitrile and toluene) over the temperature range 278 K -323 K. The ideal solubility has been estimated from calorimetric data, and solution activity coefficients at saturation in the five solvents determined. All solutions show positive deviation from Raoult's law, and all van't Hoff plots of solubility data are non-linear. The solubility in toluene is well below that observed in the other investigated solvents. Solubility data has been correlated and extrapolated to the melting point using a semiempirical regression model.

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Section: Thermodynamic Stability Relationship Of Tolbutamide Polymorphssupporting

confidence: 79%

Section: Thermodynamic Stability Relationship Of Tolbutamide Polymorphsmentioning

confidence: 74%

Section: Thermodynamic Stability Relationship Of Tolbutamide Polymorphsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Thermodynamic Stability Analysis of Tolbutamide Polymorphs and Solubility in Organic Solvents

Svärd

Valavi

Khamar

et al. 2016

Journal of Pharmaceutical Sciences

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Polymorphism: Fundamentals and Applications

Aitipamula

Nangia

2012

Supramolecular Chemistry

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Polymorphism is the ability of a compound to exist in more than one crystalline modification through different arrangements of the molecules in the solid state. Polymorphism has enormous economic and practical implications because of its ability to alter the physical and chemical properties of active pharmaceutical ingredients. The identification and complete characterization of polymorphs in the early stages of drug development is a necessary step to avoid serious financial setback in drug development and manufacturing. Thanks to new techniques such as high‐throughput screening and advances in analytical methods it has become possible to explore solid‐form diversity even with a small amount of sample in a short time. This chapter attempts to provide an overview of the fundamentals of polymorphism and the factors that control the crystallization of polymorphs. The potential implications of polymorphism in the pharmaceutical industry are highlighted with some recent examples.

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Metal‐Catalyzed Organic Reactions by Resonant Acoustic Mixing**

Gonnet

Lennox

et al. 2022

Angewandte Chemie

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We demonstrate catalytic organic synthesis by Resonant Acoustic Mixing (RAM): a mechanochemical methodology that does not require bulk solvent or milling media. Using as model reactions ruthenium‐catalyzed ring‐closing metathesis and copper‐catalyzed sulfonamide‐isocyanate coupling, RAM mechanosynthesis is shown to be faster, operationally simpler than conventional ball‐milling, while also providing the first example of a mechanochemical strategy for ruthenium‐catalyzed ene‐yne metathesis. Reactions by RAM are readily and directly scaled‐up without any significant changes in reaction conditions, as shown by the straightforward 200‐fold scaling‐up of the synthesis of the antidiabetic drug Tolbutamide, from hundreds of milligrams directly to 30 grams.

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Conformational Polymorphism of Tolbutamide: A Structural, Spectroscopic, and Thermodynamic Characterization of Burger’s Forms I–IV

Cited by 67 publications

References 41 publications

Thermodynamic Stability Analysis of Tolbutamide Polymorphs and Solubility in Organic Solvents

Thermodynamic Stability Analysis of Tolbutamide Polymorphs and Solubility in Organic Solvents

Polymorphism: Fundamentals and Applications

Metal‐Catalyzed Organic Reactions by Resonant Acoustic Mixing**

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