title: Physicochemical Properties of Bosentan and Selected PDE-5 Inhibitors in the Design of Drugs for Rare Diseases.
abstract: The study provides the physicochemical characteristic of bosentan (BOS) in comparison to tadalafil (TA) and sildenafil citrate (SIL). Despite some reports dealing with thermal characteristic of SIL and TA, physicochemical properties of BOS have not been investigated so far. Recent clinical reports have indicated that the combination of bosentan and PDE-5 inhibitor can improve the effectiveness of pharmacotherapy of pulmonary arterial hypertension (PAH). However, in order to design personalized medicines for therapy of chronic rare diseases, detailed information on the thermal behaviour and solubility of each drug is indispensable. Thus, XRD, DSC and TGA-QMS analyses were applied to compare the properties of the drugs, their thermal stability as well as to identify the products of thermal degradation. The dehydration of BOS started at 70°C and was followed by the chemical degradation with the onset at 290°C. The highest thermal stability was stated for TA, which decomposed at ca. 320°C, whereas the lowest onset of the thermal decomposition process was stated for SIL, i.e. 190°C. The products of the drug decomposition were identified. FT-FIR was applied to study intra- and intermolecular interactions between the drug molecules. FT-MIR and Raman spectroscopy were used to examine the chemical structure of the drugs. Chemoinformatic tools were used to predict the polar surface area, pKa, or logP of the drugs. Their results were in line with solubility and dissolution studies.
authors: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical College, Jagiellonian University, 9 Medyczna str, 30-688, Cracow, Poland. a.krupa@uj.edu.pl.
authors: Anna
authors: A
authors: Krupa
authors: Department of Chemistry, Jagiellonian University, Cracow, Poland.
authors: Dorota
authors: D
authors: Majda
authors: AGH - University of Science and Technology, Cracow, Poland.
authors: Włodzimierz
authors: W
authors: Mozgawa
authors: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical College, Jagiellonian University, 9 Medyczna str, 30-688, Cracow, Poland.
authors: Jakub
authors: J
authors: Szlęk
authors: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical College, Jagiellonian University, 9 Medyczna str, 30-688, Cracow, Poland.
authors: Renata
authors: R
authors: Jachowicz
mesh_terms: D000077300:Bosentan; D015195:Drug Design; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D058986:Phosphodiesterase 5 Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D035583:Rare Diseases / Q000188:drug therapy*; D000068677:Sildenafil Citrate / Q000737:chemistry; D013449:Sulfonamides / Q000737:chemistry*; D000068581:Tadalafil / Q000737:chemistry
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D013449:Sulfonamides; D000068581:Tadalafil; D000068677:Sildenafil Citrate; D000077300:Bosentan
keywords: bosentan; chemoinformatics; combination drugs; dissolution; sildenafil; tadalafil; thermal properties