Host-Guest Interaction Study of Olmesartan Medoxomil with ß-Cyclodextrin Derivatives.

Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor water solubility, leading to poor bioavailability. Encapsulation of the drug substance by two methylated cyclodextrins, namely randomly methylated ß-cyclodextrin (RM-ß-CD) and heptakis(2,3,6-tri-O-methyl)-ß-cyclodextrin (TM-ß-CD), was carried out to overcome the limitation related to OLM solubility, which, in turn, is expected to result in an improved biopharmaceutical profile. Supramolecular entities were evaluated by means of thermoanalytical techniques (TG-thermogravimetry; DTG-derivative thermogravimetry), spectroscopic methods including powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier-transform infrared (UATR-FTIR) and UV spectroscopy, saturation solubility studies, and by a theoretical approach using molecular modeling. The phase solubility method reveals an AL-type diagram for both inclusion complexes, indicating a stoichiometry ratio of 1:1. The values of the apparent stability constant indicate the higher stability of the host-guest system OLM/RM-ß-CD. The physicochemical properties of the binary systems are different from those of the parent compounds, emphasizing the formation of inclusion complexes between the drug and CDs when the kneading method was used. The molecular encapsulation of OLM in RM-ß-CD led to an increase in drug solubility, thus the supramolecular adduct can be the subject of further research to design a new pharmaceutical formulation containing OLM, with improved bioavailability.

Comorbidities, Treatment and Survival Rates of Chronic Thromboembolic Pulmonary Hypertension in a Regional Centre.

Background/Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by a multitude of underlying causes, treatment modalities and prognostic outcomes. Our aim was to evaluate the underlying causes, comorbidities and survival rates of CTEPH patients. Methods: A retrospective analysis was conducted regarding the evolution of CTEPH patients confirmed by right heart catheterization under treatment with specific vasodilator medication in our centre between 2008 and 2023. Results: We treated 14 CTEPH patients, 78.57% female, 52.79 ± 13.64 years at inclusion, representing 11.29% of our pulmonary arterial hypertension registry. Initially, the distribution of patients' NYHA class was II-14.28%, III-71.42% and IV-14.28%. In total, 71.42% of these patients were technically operable due to the central location of the thrombus, but 42.85% presented severe comorbidities and 28.57% refused the surgery or it was financially inaccessible. Only four patients were operated on by pulmonary endarterectomy (PEA). Unfortunately, all the post-PEA patients had persistent pulmonary hypertension and had to continue vasodilator treatment. Overall, 64.28% of patients had monotherapy, 21.42% double therapy and 14.28% triple therapy. Regarding underlying causes and comorbidities, we found the following incidences: 78.57% chronic venous insufficiency, 42.85% obesity, 35.71% thyroid disease, hypertension and hyperuricemia, 21.42% thrombophilia and ischemic heart disease, 14.28% atrial fibrillation, vasculitis and lung disease, and 14.28% neoplastic history and diabetes. Seven patients died (50%), six of whom were unoperated and one of whom was lost (abandoned the program). The survival rates at 1, 3, 5 and 7 years for unoperated patients were 100%, 58.3%, 29.2% and 29.2% versus 100%, 75%, 75% and 75% in post-PEA patients. Conclusions: CTEPH, marked by delayed diagnosis, multiple comorbidities and limited intervention options, requires proactive screening and comprehensive multimodal therapies, including PEA, to improve survival rates.

Host-Guest Complexation of Itraconazole with Cyclodextrins for Bioavailability Enhancement.

Itraconazole is an antifungal agent included in the triazole pharmacological classification that belongs to the BCS class II, characterized by a low solubility in an aqueous medium (of 1 ng/mL, at neutral pH), which is frequently translated in a low oral bioavailability but with a high permeability. In this sense, it is necessary to find solutions to increase/improve the solubility of itraconazole in the aqueous environment. The main purpose of this study is the preparation and analysis of five different guest-host inclusion complexes containing intraconazole. Initially, a blind docking process was carried out to determine the interactions between itraconazole and the selected cyclodextrins. The second step of the study was to find out if the active pharmaceutical ingredient was entrapped in the cavity of the cyclodextrin, by using spectroscopic and thermal techniques. Also, the antifungal activity of the inclusion complexes was studied to examine if the entrapment of itraconazole influences the therapeutic effect. The results showed that the active substance was entrapped in the cavity of the cyclodextrins, with a molar ratio of 1:3 (itraconazole-cyclodextrin), and that the therapeutic effect was not influenced by the entrapment.