{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T19:57:28Z","timestamp":1776715048812,"version":"3.51.2"},"reference-count":60,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EK\u00d6P-2024-128 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund","award":["NKFIH FK 146930"],"award-info":[{"award-number":["NKFIH FK 146930"]}]},{"name":"National Research, Development, and Innovation Office, Hungary","award":["NKFIH FK 146930"],"award-info":[{"award-number":["NKFIH FK 146930"]}]},{"name":"EK\u00d6P-24-4-I-BME-127 University Research Fellowship Programme of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund","award":["NKFIH FK 146930"],"award-info":[{"award-number":["NKFIH FK 146930"]}]},{"name":"J\u00e1nos Bolyai Research Scholarship of the Hungarian Academy of Sciences","award":["NKFIH FK 146930"],"award-info":[{"award-number":["NKFIH FK 146930"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Early diagnosis and oral or, in severe cases, intravenous antibiotics are usually effective for Lyme disease, but some patients have persistent symptoms unresponsive to standards of care, requiring alternative therapies. Disulfiram (DIS), a drug for alcoholism, is under investigation as a potential adjunctive treatment, but its low bioavailability, rapid metabolism, and safety concerns urge the development of improved formulations for clinical translation. Methods: Screening dissolution and permeation studies were investigated for vehicle and excipient selection, following the pharmacopeia perspectives to develop and optimize the low-dose DIS rectal suppository intended for application in post-treatment Lyme disease syndrome (PTLDS). Further characterizations were carried out by differential scanning calorimetry, X-ray diffraction, and infrared spectroscopy. Results: Cyclodextrin (CD) encapsulation was investigated to improve the aqueous solubility of the hydrophobic drug. The dissolution of DIS from fatty base suppository was very slow; it was remarkably improved by the molecular encapsulation of the drug with CDs. The dissolution of DIS from a water-soluble base was more favorable, but incomplete. In the polyethylene glycol (PEG) based suppositories, the addition of CDs already in a physical mixture ensured the dissolution of the drug. The presented drug delivery system relates to a novel preparation for rectal administration comprising a low-dose disulfiram with improved solubility and permeability by the PEG and hydroxypropyl-\u03b2-cyclodextrin (HPBCD) synergistic matrix. Conclusions: The rectal dosage form containing the drug and CD in the physical mixture is advantageous, avoiding the hepatic first-pass effect, minimizing dose-limiting toxicity, simplifying production, and fasting the availability of the repositioned drug.<\/jats:p>","DOI":"10.3390\/pharmaceutics17070849","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T06:46:12Z","timestamp":1751438772000},"page":"849","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of Low-Dose Disulfiram Rectal Suppository Intended for Application in Post-Treatment Lyme Disease Syndrome"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3608-6219","authenticated-orcid":false,"given":"Be\u00e1ta-M\u00e1ria","family":"Benk\u0151","sequence":"first","affiliation":[{"name":"University Pharmacy Department of Pharmacy Administration, Semmelweis University, H\u0151gyes Endre u. 7-9, 1092 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1lint-Imre","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Egis Pharmaceuticals Plc., R&D Directorate, 1475 Budapest, Hungary"},{"name":"Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, Szent Gell\u00e9rt t\u00e9r 4, 1111 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Szabina","family":"K\u00e1d\u00e1r","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, M\u0171egyetem rkp. 3, 1111 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9616-5122","authenticated-orcid":false,"given":"Edina","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, M\u0171egyetem rkp. 3, 1111 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5341-319X","authenticated-orcid":false,"given":"Gerg\u0151","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Semmelweis University, H\u0151gyes Endre u. 7-9, 1092 Budapest, Hungary"},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lajos","family":"Szente","sequence":"additional","affiliation":[{"name":"CycloLab Cyclodextrin Research & Development Laboratory Ltd., Illatos \u00fat 7, 1097 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e9ter","family":"Tonka-Nagy","sequence":"additional","affiliation":[{"name":"Egis Pharmaceuticals Plc., R&D Directorate, 1475 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5419-9137","authenticated-orcid":false,"given":"Rom\u00e1na","family":"Zelk\u00f3","sequence":"additional","affiliation":[{"name":"University Pharmacy Department of Pharmacy Administration, Semmelweis University, H\u0151gyes Endre u. 7-9, 1092 Budapest, Hungary"},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Istv\u00e1n","family":"Sebe","sequence":"additional","affiliation":[{"name":"University Pharmacy Department of Pharmacy Administration, Semmelweis University, H\u0151gyes Endre u. 7-9, 1092 Budapest, Hungary"},{"name":"Egis Pharmaceuticals Plc., R&D Directorate, 1475 Budapest, Hungary"},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Amponsah, S.K., Shegokar, R., and Pathak, Y.V. 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