{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T10:58:57Z","timestamp":1785841137840,"version":"3.56.0"},"reference-count":50,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VICTOR BABES UNIVERSITY OF MEDICINE AND PHARMACY TIMISOARA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: In the past two decades, the primary therapeutic use of sildenafil has shifted significantly, from the treatment of angina to managing erectile dysfunction, and since the early 2000s it has been used in the treatment of pulmonary hypertension, particularly pulmonary arterial hypertension. Sildenafil is used as a citrate salt; after oral administration, it presents an absorption of ~90% and an absolute bioavailability of 38%, due to the first-pass effect, such that it belongs to class II of the Biopharmaceutics Classification System. Currently, studies are seeking to obtain new pharmaceutical formulations with an optimized biopharmaceutical profile. In this study, an inclusion complex of sildenafil citrate and 2-hydroxypropyl-beta-cyclodextrin in a molar ratio of 1:1 was obtained and its pharmaceutical compatibility with six pharmaceutical excipients was assessed. For three of these excipients, the presence of chemical interactions with sildenafil citrate has been presented in the literature, and for the other three, compatibility has not been evaluated. Methods: To certify the stoichiometry of the obtained inclusion complex molecular modeling, Job\u2019s method and the Benesi\u2013Hildebrand method were employed. Furthermore, we have described the inclusion complex and the obtained binary mixtures via ATR-FTIR and thermal (TG\/DTG and DSC) analysis. Results: The results indicated a lack of chemical interactions between the inclusion complex and the six pharmaceutical excipients at ambient temperature (confirmed by ATR\u2013FTIR investigations) and the presence of chemical interactions between the inclusion complex and three of the excipients when the mixture was heated under non-isothermal conditions (TG\/DTG and DSC investigations). Conclusions: This study describes the inclusion complex between sildenafil citrate and 2-hydroxypropyl-beta-cyclodextrin in a molar ratio of 1:1 and its compatibility with several pharmaceutical excipients, results with further applications in the preformulation stage of novel delivery systems.<\/jats:p>","DOI":"10.3390\/pharmaceutics17091114","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T08:19:32Z","timestamp":1756282772000},"page":"1114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Compatibility Studies of Sildenafil-HPBCD Inclusion Complex with Pharmaceutical Excipients"],"prefix":"10.3390","volume":"17","author":[{"given":"R\u0103zvan Adrian","family":"Bertici","sequence":"first","affiliation":[{"name":"Doctoral School, \u201cVictor Babe\u015f\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Center for Research and Innovation in Personalised Medicine of Respiratory Diseases, Pulmonology University Clinic, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3921-2518","authenticated-orcid":false,"given":"Amalia","family":"Ridichie","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Advanced Instrumental Screening Center, Faculty of Pharmacy, \u201cVictor Babe\u015f\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9391-0200","authenticated-orcid":false,"given":"Nicoleta Sorina","family":"Bertici","sequence":"additional","affiliation":[{"name":"Center for Research and Innovation in Personalised Medicine of Respiratory Diseases, Pulmonology University Clinic, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Pulmonary Hypertension Treatment Unit, Center of Expertise for Adult Rare Respiratory Diseases, Clinical Hospital of Infectious Diseases and Pneumophthisiology \u201cDr. Victor Babes\u201d, 13 Gheorghe Adam Str., 300310 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3462-1863","authenticated-orcid":false,"given":"Adriana","family":"Lede\u0163i","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Advanced Instrumental Screening Center, Faculty of Pharmacy, \u201cVictor Babe\u015f\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7603-9700","authenticated-orcid":false,"given":"Ionu\u0163","family":"Lede\u0163i","sequence":"additional","affiliation":[{"name":"Advanced Instrumental Screening Center, Faculty of Pharmacy, \u201cVictor Babe\u015f\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Department of Physical Chemistry, Faculty of Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata-Maria","family":"V\u0103ru\u0163","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Medicine and Pharmacy Craiova, 2-4 Petru Rares Str., 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-4909","authenticated-orcid":false,"given":"Laura","family":"Sb\u00e2rcea","sequence":"additional","affiliation":[{"name":"Advanced Instrumental Screening Center, Faculty of Pharmacy, \u201cVictor Babe\u015f\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Department of Drug Analysis, Faculty of Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Albu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, \u201cVasile Goldi\u0219\u201d Western University of Arad, 86 L. Rebreanu Str., 310414 Arad, Romania"},{"name":"National Institute for Economic Research \u201cCenter for Mountain Economy (CE-MONT), Costin C. Kiritescu\u201d of the Romanian Academy, 49 Petreni St., 725700 Vatra Dornei, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilda","family":"R\u0103dulescu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Division of Microbiology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7632-8657","authenticated-orcid":false,"given":"Gerlinde","family":"Rusu","sequence":"additional","affiliation":[{"name":"Faculty of Chemical Engineering Biotechnologies and Environmental Protection, University Politehnica Timisoara, 6 Vasile Parvan Boulevard, 300223 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7827-818X","authenticated-orcid":false,"given":"Drago\u0219 C\u0103t\u0103lin","family":"Jianu","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, First Division of Neurology, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Advanced Centre for Cognitive Research in Neuropsychiatric Pathology (NeuroPsy-Cog), Department of Neurosciences-VIII, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timi\u0219oara, 156 L. Rebreanu Ave., 300736 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9034-5218","authenticated-orcid":false,"given":"Ovidiu","family":"Fira-Mladinescu","sequence":"additional","affiliation":[{"name":"Center for Research and Innovation in Personalised Medicine of Respiratory Diseases, Pulmonology University Clinic, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Pulmonary Hypertension Treatment Unit, Center of Expertise for Adult Rare Respiratory Diseases, Clinical Hospital of Infectious Diseases and Pneumophthisiology \u201cDr. Victor Babes\u201d, 13 Gheorghe Adam Str., 300310 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/nrd2030","article-title":"Sildenafil: From Angina to Erectile Dysfunction to Pulmonary Hypertension and Beyond","volume":"5","author":"Ghofrani","year":"2006","journal-title":"Nat. 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