Solvatomorphism of the Antibacterial Dapsone: X-ray Structures and Thermal Desolvation Kinetics

Lemmer, H.J.R.; Stieger, Nicóle; Liebenberg, Wilna; Caira, Mino R.

doi:10.1021/cg300019f

Cited by 31 publications

(27 citation statements)

References 22 publications

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“…The compound DPS is a drug that is used to treat infectious diseases including leprosy, tuberculosis, malaria and AIDS-related pneumonia [ 45 ]. DPS was intercalated in a media containing 1N HCl at pH ~2.0.…”

Section: Resultsmentioning

confidence: 99%

Sodium Montmorillonite/Amine-Containing Drugs Complexes: New Insights on Intercalated Drugs Arrangement into Layered Carrier Material

et al. 2015

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Layered drug delivery carriers are current targets of nanotechnology studies since they are able to accommodate pharmacologically active substances and are effective at modulating drug release. Sodium montmorillonite (Na-MMT) is a clay that has suitable properties for developing new pharmaceutical materials due to its high degree of surface area and high capacity for cation exchange. Therefore Na-MMT is a versatile material for the preparation of new drug delivery systems, especially for slow release of protonable drugs. Herein, we describe the intercalation of several amine-containing drugs with Na-MMT so we can derive a better understanding of how these drugs molecules interact with and distribute throughout the Na-MMT interlayer space. Therefore, for this purpose nine sodium montmorillonite/amine-containing drugs complexes (Na-MMT/drug) were prepared and characterized. In addition, the physicochemical properties of the drugs molecules in combination with different experimental conditions were assessed to determine how these factors influenced experimental outcomes (e.g. increase of the interlayer spacing versus drugs arrangement and orientation). We also performed a molecular modeling study of these amine-containing drugs associated with different Na-MMT/drug complex models to analyze the orientation and arrangement of the drugs molecules in the complexes studied. Six amine-containing drugs (rivastigmine, doxazosin, 5-fluorouracil, chlorhexidine, dapsone, nystatin) were found to successfully intercalate Na-MMT. These findings provide important insights on the interlayer aspect of the molecular systems formed and may contribute to produce more efficient drug delivery nanosystems.

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Section: Resultsmentioning

confidence: 99%

Sodium Montmorillonite/Amine-Containing Drugs Complexes: New Insights on Intercalated Drugs Arrangement into Layered Carrier Material

et al. 2015

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“…Single crystal structures are known for anhydrate forms III (Dickinson et al, 1970 ; Deo et al, 1980 ; Bocelli and Cantoni, 1990 ; Su et al, 1992 ; Bertolasi et al, 1993 ) and II (Braun et al, 2017 ). It is also known that DDS forms solvates with dichloromethane, 1,4-dioxane and tetrahydrofuran (Babashkina et al, 2012 ; Lemmer et al, 2012 ). Furthermore, several crystal structure determinations of a hydrate with the unusual DDS:water stoichiometry of 3:1 (0.33-hydrate) have been reported (Kuz'mina et al, 1981 ; Bel'skii et al, 1983 ; Yathirajan et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Supramolecular Organization of Nonstoichiometric Drug Hydrates: Dapsone

Braun

Griesser

2018

Front. Chem.

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The observed moisture- and temperature dependent transformations of the dapsone (4,4′-diaminodiphenyl sulfone, DDS) 0. 33-hydrate were correlated to its structure and the number and strength of the water-DDS intermolecular interactions. A combination of characterization techniques was used, including thermal analysis (hot-stage microscopy, differential scanning calorimetry and thermogravimetric analysis), gravimetric moisture sorption/desorption studies and variable humidity powder X-ray diffraction, along with computational modeling (crystal structure prediction and pair-wise intermolecular energy calculations). Depending on the relative humidity the hydrate contains between 0 and 0.33 molecules of water per molecule DDS. The crystal structure is retained upon dehydration indicating that DDS hydrate shows a non-stoichiometric (de)hydration behavior. Unexpectedly, the water molecules are not located in structural channels but at isolated-sites of the host framework, which is counterintuitively for a hydrate with non-stoichiometric behavior. The water-DDS interactions were estimated to be weaker than water-host interactions that are commonly observed in stoichiometric hydrates and the lattice energies of the isomorphic dehydration product (hydrate structure without water molecules) and (form III) differ only by ~1 kJ mol−1. The computational generation of hypothetical monohydrates confirms that the hydrate with the unusual DDS:water ratio of 3:1 is more stable than a feasible monohydrate structure. Overall, this study highlights that a deeper understanding of the formation of hydrates with non-stoichiometric behavior requires a multidisciplinary approach including suitable experimental and computational methods providing a firm basis for the development and manufacturing of high quality drug products.

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“…With the exception of Hydehy, the six lowest energy packings show structural resemblance. One low density structure can be found in Figure 11, which corresponds to the isomorphic desolvate of the DDS dichloromethane hemisolate 40 . Figure 11.…”

Section: Computationally Generated Anhydrate Crystal Energy Landscapementioning

confidence: 99%

Dapsone Form V: A Late Appearing Thermodynamic Polymorph of a Pharmaceutical

2019

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Five anhydrate polymorphs (Forms I-V) and the isomorphic dehydrate (Hydehy) of dapsone (4,4′diaminodiphenyl sulfone or DDS) were prepared and characterized in an interdisciplinary experimental and computational study, elucidating the kinetic and thermodynamic stabilities, solid form interrelationships and structural features of the known forms I-IV, the novel polymorph Form V, and Hydehy. Calorimetric measurements, solubility experiments and lattice energy calculations revealed that Form V is the thermodynamically stable polymorph from absolute zero to at least 90 C. At higher temperatures Form II and then Form I becomes the most stable DDS solid form. The computed 0 K stability order (lattice energy calculations) was confirmed with calorimetric measurements as follows: V (most stable) > III > Hydehy > II > I > IV (least stable). The discovery of Form V was complicated by the fact that the metastable but kinetically stabilized Form III shows a higher nucleation and growth rate. By combining laboratory powder X-ray diffraction data and ab initio calculations, the crystal structure of Form V (P21/c, Z′=4) was solved, with a high energy DDS conformation allowing a denser packing and more stable intermolecular interactions, rationalizing the formation of a high Z′ structure. The structures of the Forms I and IV, only observed from the melt and showing distinct packing features compared to the Forms II, III, and V, were derived from the computed crystal energy landscapes. Dehydration modelling of the DDS hydrate lead to the Hydehy structure. This study expands our understanding about the complex crystallization behavior of pharmaceuticals and highlights the big challenge in solid form screening, especially that there is no clear end point.

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Solvatomorphism of the Antibacterial Dapsone: X-ray Structures and Thermal Desolvation Kinetics

Cited by 31 publications

References 22 publications

Sodium Montmorillonite/Amine-Containing Drugs Complexes: New Insights on Intercalated Drugs Arrangement into Layered Carrier Material

Sodium Montmorillonite/Amine-Containing Drugs Complexes: New Insights on Intercalated Drugs Arrangement into Layered Carrier Material

Supramolecular Organization of Nonstoichiometric Drug Hydrates: Dapsone

Dapsone Form V: A Late Appearing Thermodynamic Polymorph of a Pharmaceutical

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