The influence of the preparation methods on the inclusion of model drugs in a β-cyclodextrin cavity

NOTICE: this is the author’s version of a work that was accepted for publication in European Journal of Pharmaceutics and Biopharmaceutics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Eur J Pharm Biopharm. 2009 Feb;71(2):377-386. Epub 2008 Oct 17.The work aims to prove the complexation of two model drugs (ibuprofen, IB and indomethacin, IN) by bcyclodextrin (bCD), and the effect of water in such a process, and makes a comparison of their complexation yields. Two methods were considered: kneading of a binary mixture of the drug, bCD, and inclusion of either IB or IN in aqueous solutions of bCD. In the latter method water was removed by air stream, spray-drying and freeze-drying. To prove the formation of complexes in final products, optical microscopy, UV spectroscopy, IR spectroscopy, DSC, X-ray and NMR were considered. Each powder was added to an acidic solution (pH = 2) to quantify the concentration of the drug inside bCD cavity. Other media (pH = 5 and 7) were used to prove the existence of drug not complexed in each powder, as the drugs solubility increases with the pH. It was observed that complexation occurred in all powders, and that the fraction of drug inside the bCD did not depend neither on the method of complexation nor on the processes of drying considered

Wirkung von oralen und nasalen antiseptischen Phthalocyanin-Lösungen auf die Infektiosität von SARS-CoV-2 bei Patienten mit COVID-19: eine randomisierte kontrollierte Studie

Background: In individuals with coronavirus disease (COVID-19), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (VL) plays an important role in infectivity.Objectives: This study aimed to evaluate the reduction in the VL and infectivity induced by phthalocyanine mouthwash and nasal spray in patients with COVID-19.Methods: Patients with mild COVID-19 were recruited to participate in a triple-blinded randomized controlled trial. Participants were assigned to one of three groups: Group 1, non-active mouthwash and saline nasal spray (SNS); Group 2, phthalocyanine mouthwash and SNS; and Group 3 phthalocyanine mouthwash and phthalocyanine nasal spray. VL was assessed in nasopharyngeal and oropharyngeal swabs collected at the time of clinical diagnosis at baseline as well as 24 and 72 hours after starting the rinsing protocols.Findings: Forty-six participants were included in the analysis: 15, 16, and 15 in Groups 1, 2, and 3, respectively. After 72 hours, the reduction in VL was significantly higher in Group 3 (mean cycle threshold (Ct) decrease: 11.21) than in Group 1 (mean Ct decrease: 5.53). Additionally, only the mean VL in Group 3 was reduced to a non-contagious level after 72 hours.Main conclusions: Use of phthalocyanine mouthwash and nasal spray is effective at reducing SARS-CoV-2 infectivity.Hintergrund: Bei Personen mit Coronavirus-Erkrankung (COVID-19) spielt die Viruslast (VL) des schweren akuten respiratorischen Syndroms Coronavirus 2 (SARS-CoV-2) eine wichtige Rolle für die Infektiosität.Zielsetzungen: Ziel dieser Studie war es, die Verringerung der VL und der Infektiosität durch Phthalocyanin-Mundwasser und -Nasenspray bei Patienten mit COVID-19 zu untersuchen.Methoden: Patienten mit leichter COVID-19-Erkrankung wurden für die Teilnahme an einer dreifachblinden, randomisierten und kontrollierten Studie rekrutiert. Die Teilnehmer wurden einer von drei Gruppen zugeteilt: Gruppe 1: nicht-aktive Mundspülung und Kochsalz-Nasenspray; Gruppe 2: Phthalocyanin-Mundspülung und Kochsalz-Nasenspray und Gruppe 3: Phthalocyanin-Mundspülung und Phthalocyanin-Nasenspray. VL wurde in nasopharyngealen und oropharyngealen Abstrichen untersucht, die zum Zeitpunkt der klinischen Diagnose zu Studienbeginn sowie 24 und 72 Stunden nach Beginn der Spülprotokolle entnommen wurden.Ergebnisse: In die Analyse wurden 46 Teilnehmer einbezogen: 15 in Gruppe 1, 16 in Gruppe 2 und 15 in Gruppe 3. Nach 72 Stunden war die Verringerung der VL in Gruppe 3 signifikant höher (mittlere Abnahme der Zyklusschwelle: 11,21) als in Gruppe 1 (mittlere Abnahme der Zyklusschwelle: 5,53). Außerdem war nur die mittlere VL in Gruppe 3 nach 72 Stunden auf ein nicht-ansteckendes Niveau gesunken.Wichtigste Schlussfolgerungen: Die Verwendung von Phthalocyanin-Mundspülungen und -Nasensprays ist wirksam bei der Verringerung der SARS-CoV-2-Infektiosität