Co‐crystallization with Nicotinamide in Two Conformations Lowers Energy but Expands Volume

Zhang, Siwei; Kendrick, John; Leusen, Frank J. J.; Yu, Lian

doi:10.1002/jps.23929

Cited by 10 publications

(12 citation statements)

References 36 publications

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“…It is plausible that the additional hydrogen bonding could form part of the explanation why the cocrystal has a more open structure than the pure component crystals. Indeed, similar observations have been made for nicotinamide–mandelic acid cocrystals …”

Section: Evaluation and Discussionsupporting

confidence: 81%

“…In an approximate approach, relative lattice energies of cocrystals and their crystalline components may be compared. This offers a method to computationally predict the occurrence of cocrystals. , However, a method based on lattice energies neglects the influence of entropy on the propensity for cocrystal formation, and moreover, computational methods for calculation of lattice energies often neglect zero-point energies as well as thermal effects. , …”

Section: Theorymentioning

confidence: 99%

See 1 more Smart Citation

Calorimetric Determination of Cocrystal Thermodynamic Stability: Sulfamethazine–Salicylic Acid Case Study

Svärd

Ahuja

Rasmuson

2020

Crystal Growth & Design

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This work demonstrates how the thermodynamics of cocrystal formation from the pure, solid coformers can be directly determined from experimentally obtained calorimetric data, without involving solubility data or approximations of ideal solution. For the 1:1 cocrystal between the drug API sulfamethazine and salicylic acid, the melting temperatures and associated enthalpies of fusion have been determined for the coformers in their respective pure solid state and as an equimolar physical mixture and for the cocrystal, using differential scanning calorimetry. Heat capacities have been determined for the respective solid forms and their supercooled melts. The Gibbs energy for cocrystal formation and the enthalpic and entropic components have been determined as functions of temperature through a thermodynamic cycle. The Gibbs energy, enthalpy, and entropy of mixing have been estimated from the thermodynamic functions for cocrystal formation and fusion of the solid phases. The results show that the Gibbs energy for cocrystal formation is negative, i.e. the cocrystal is the stable solid phase in relation to a 1:1 mixture of the coformers throughout the temperature interval from room temperature to the cocrystal melting point, and becomes increasingly negative with increasing temperature. Cocrystal formation is an endothermic process, driven by the favorable entropy increase, and is accompanied by a 6% increase in molecular volume. At room temperature, liquid mixing of coformers is found to be weakly exothermic. The results qualitatively align with a previously reported analysis based on solubility data.

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Section: Evaluation and Discussionsupporting

confidence: 81%

Section: Theorymentioning

confidence: 99%

Calorimetric Determination of Cocrystal Thermodynamic Stability: Sulfamethazine–Salicylic Acid Case Study

Svärd

Ahuja

Rasmuson

2020

Crystal Growth & Design

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“…Molecular components are often less packed in cocrystals than in other crystals (e.g., salts). 24) Also, non-ionic interactions constructing the cocrystals, such as hydrogen bonding, halogen bonding, π-π stacking, and van der Waals forces, are weaker than ionic interactions. In addition to several cocrystals composed of non-ionic APIs and coformers, some crystals containing salts of APIs and coformers interacting in a non-ionic manner satisfy the aforestated definition (i.e., ionic cocrystals).…”

Section: Structure Of Cocrystalsmentioning

confidence: 99%

Characterization and Quality Control of Pharmaceutical Cocrystals

Izutsu¹,

Koide²,

Takata

et al. 2016

Chem. Pharm. Bull.

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Recent active research and new regulatory guidance on pharmaceutical cocrystals have increased the rate of their development as promising approaches to improve handling, storage stability, and bioavailability of poorly soluble active pharmaceutical ingredients (APIs). However, their complex structure and the limited amount of available information related to their performance may require development strategies that differ from those of single-component crystals to ensure their clinical safety and efficacy. This article highlights current methods of characterizing pharmaceutical cocrystals and approaches to controlling their quality. Different cocrystal regulatory approaches between regions are also discussed. The physical characterization of cocrystals should include elucidating the structure of their objective crystal form as well as their possible variations (e.g., polymorphs, hydrates). Some solids may also contain crystals of individual components. Multiple processes to prepare pharmaceutical cocrystals (e.g., crystallization from solutions, grinding) vary in their applicable ingredients, scalability, and characteristics of resulting solids. The choice of the manufacturing method affects the quality control of particular cocrystals and their formulations. In vitro evaluation of the properties that govern clinical performance is attracting increasing attention in the development of pharmaceutical cocrystals. Understanding and mitigating possible factors perturbing the dissolution and/ or dissolved states, including solution-mediated phase transformation (SMPT) and precipitation from supersaturated solutions, are important to ensure the bioavailability of orally administrated lower-solubility APIs. The effect of polymer excipients on the performance of APIs emphasizes the relevance of formulation design for appropriate use.

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“…15,25 It is noted that the difference between ΔE f and ΔG f is the entropy term, as ΔE f is approximate to ΔH f at ambient conditions. 26 Therefore, correlating ΔE f with cocrystal stability assumes that enthalpy is the major component of free energy and the main driving force of cocrystallization.…”

Section: ■ Introductionmentioning

confidence: 99%

Celecoxib–Nicotinamide Cocrystal Revisited: Can Entropy Control Cocrystal Formation?

Zhang

Brunskill

Schwartz

et al. 2017

Crystal Growth & Design

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The cocrystal of celecoxib–nicotinamide has been revisited to reveal its crystal structure and unusual formation properties. Gibbs free energy and enthalpy of formation at 25 °C were determined by solubility and thermal analysis. The formation of celecoxib–nicotinamide was found to be an endothermic process and driven by entropy, a mechanism different from many reported cocrystals but in agreement with previously reported lattice energy calculation. The cocrystal is stable only above a transition temperature as predicted from thermodynamic data and confirmed experimentally. This formation mechanism provides new opportunities for cocrystal research from structural prediction to process development and enriches our understanding of the nature of cocrystallization.

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Co‐crystallization with Nicotinamide in Two Conformations Lowers Energy but Expands Volume

Cited by 10 publications

References 36 publications

Calorimetric Determination of Cocrystal Thermodynamic Stability: Sulfamethazine–Salicylic Acid Case Study

Calorimetric Determination of Cocrystal Thermodynamic Stability: Sulfamethazine–Salicylic Acid Case Study

Characterization and Quality Control of Pharmaceutical Cocrystals

Celecoxib–Nicotinamide Cocrystal Revisited: Can Entropy Control Cocrystal Formation?

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