Supramolecular Organization of Nonstoichiometric Drug Hydrates: Dapsone

Abstract

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.

Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties

“…Of note, the same anti-conformation was found in both Form B and C [19,20]. Moreover, the water molecules are not linked to each other but are instead connected with the drug molecule, meaning that the new PZQ-HH belongs to the isolated-site hydrates [31,46].…”

“…As a consequence, hydrates are commonly classified into non-stoichiometric hydrates (frequently hosting water molecules in structural voids, subjected to reversible water uptake/release without significant changes in the crystal structure) and stoichiometric hydrates (leading to a different structure or an amorphous state after the escape of water molecules) [29,30]. Based on their structure, the hydrate nomenclature can also embrace terms like isolate-site hydrates (water molecules are isolated from direct contact), channel hydrates (containing chains of water molecules) and ion-associated hydrates (where metal ions are coordinated with water) [31].…”

Intermolecular Interactions in Functional Crystalline Materials: From Data to Knowledge

“…Such channels can be not only dehydrated but also substituted with other solvents [300,301]. The solid dehydration with prominent atomic movement traced with single-crystal or powder X-Ray diffraction can shed light on a more complex mechanism of water loss [302][303][304][305][306]. Various mobility of the water clusters incorporated within the pores and H-bonding waters that structure these pores was demonstrated in Refs.…”

An Undergraduate Experiment Using Cyclodextrin – Assisted Sensitive Fluorescence Detection and Quantitation of Dapsone Drug in Wastewater Samples

“…Dapsone, also known as diaminodiphenyl sulfone (DDS), is an antibiotic drug commonly used for treatment of various skin disorders like leprosy, dermatitis and herpetiformis [1,2,3]. It has been studied extensively for pharmaceutical research such as bioavailability [4], biotransformation [5], and formulations, [6]. It has been detected in plasma, urine and saliva [7,8] using different analytical methods such as liquid chromatography with, UV-Visible [8], fluorescence [9] and mass spectrometry [10], as well as electrochemical detection [8].…”