News
16.03.2022New papers published with contributions from the polymorphism and calorimetry and DRX laboratories
FAs a result of the collaboration with researchers from the University of Barcelona and other institutions, PhD. Rafel Prohens and PhD. Rafael Barbas, of the CCiTUB Polymorphism and Calorimetry Laboratory, have published the paper "Synthesis and Characterization of a New Norfloxacin/Resorcinol Cocrystal with Enhanced Solubility and Dissolution Profile" as a result of the laboratory's methodological development studies, and "Novel Polymorphic Cocrystals of the Non-Steroidal Anti-Inflammatory Drug Niflumic Acid: Expanding the Pharmaceutical Landscape" . Both papers have been published in the journal Pharmaceutics, which is open access, is indexed in the JCR as the Q1 quartile (Pharmacology & Pharmacy) and has an impact factor of 6.3.
Likewise, PhD. Prohens and PhD. Barbas, together with PhD. Mercè Font, from the CCiTUB's DRX laboratory, have published the paper "Polymorphism in the 1/1 Pterostilbene/Picolinic Acid Cocrystal" as a result of studies carried out within the framework of collaboration with the company CIRCE. The paper has been published in the journal Crystal Growth & Design, which is indexed in the JCR as the Q1 quartile in the areas of: Chemistry, Condensed Matter Physics and Materials Science and has an impact factor of 4.0.
The abstracts of the papers are as follows:
Synthesis and Characterization of a New Norfloxacin/Resorcinol Cocrystal with Enhanced Solubility and Dissolution Profile
A new cocrystal of Norfloxacin, a poorly soluble fluoroquinolone antibiotic, has been synthetized by a solvent-mediated transformation experiment in toluene, using resorcinol as a coformer. The new cocrystal exists in both anhydrous and monohydrate forms with the same (1:1) Norfloxacin/resorcinol stoichiometry. The solubility of Norfloxacin and the hydrated cocrystal were determined by the shake-flask method. While Norfloxacin has a solubility of 0.32 ± 0.02 mg/mL, the cocrystal has a solubility of 2.64 ± 0.39 mg/mL, approximately 10-fold higher. The dissolution rate was tested at four biorelevant pH levels of the gastrointestinal tract: 2.0, 4.0, 5.5, and 7.4. In a first set of comparative tests, the dissolution rate of Norfloxacin and the cocrystal was determined separately at each pH value. Both solid forms showed the highest dissolution rate at pH 2.0, where Norfloxacin is totally protonated. Then, the dissolution rate decreases as pH increases. In a second set of experiments, the dissolution of the cocrystal was evaluated by a unique dissolution test, in which the pH dynamically changed from 2.0 to 7.4, stepping 30 min at each of the four biorelevant pH values. Results were quite different in this case, since dissolution at pH 2 affects the behavior of Norfloxacin at the rest of the pH values.The paper can be read at the follwing link:[+].
Novel Polymorphic Cocrystals of the Non-Steroidal Anti-Inflammatory Drug Niflumic Acid: Expanding the Pharmaceutical Landscape
Any time the pharmaceutical industry develops a new drug, potential polymorphic events must be thoroughly described, because in a crystalline pharmaceutical solid, different arrangements of the same active pharmaceutical ingredient can yield to very different physicochemical properties that might be crucial for its efficacy, such as dissolution, solubility, or stability. Polymorphism in cocrystal formulation cannot be neglected, either. In this work, two different cocrystal polymorphs of the non-steroidal anti-inflammatory drug niflumic acid and caffeine are reported. They have been synthesized by mechanochemical methods and thoroughly characterized in solid-state by powder and single crystal X-ray diffraction respectively, as well as other techniques such as thermal analyses, infrared spectroscopy and computational methods. Both theoretical and experimental results are in agreement, confirming a conformational polymorphism. The polymorph NIF–CAF Form I exhibits improved solubility and dissolution rate compared to NIF–CAF Form II, although Form II is significantly more stable than Form I. The conditions needed to obtain these polymorphs and their transition have been carefully characterized, revealing an intricate system.The paper can be read at the follwing link:[+].
Polymorphism in the 1/1 Pterostilbene/Picolinic Acid Cocrystal
The crystal structures of two new polymorphs of the 1/1 pterostilbene/picolinic acid cocrystal have been analyzed by single-crystal X-ray diffraction and studied by means of DFT calculations and a set of computational tools (QTAIM, NCIplot, MEP). The observation of a new R22(10) synthon in each of the two polymorphs has been analyzed energetically, characterized using the topology of the electron density, and rationalized using the MEP surfaces. The exceptional bioavailability of the cocrystal is explained on the basis of BFDH morphology calculations, and the study is complemented by a deep analysis of the supramolecular synthons formed by both neutral and zwitterionic forms of picolinic acid, a versatile coformer for crystal engineering.The paper can be read at the follwing link:[+].