Understanding the pH Dependence of Supersaturation State-A Case Study of Telmisartan.

dimerization solubility supersaturation telmisartan

Journal

Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003

Informations de publication

Date de publication:
05 Aug 2022
Historique:
received: 14 07 2022
revised: 29 07 2022
accepted: 02 08 2022
entrez: 26 8 2022
pubmed: 27 8 2022
medline: 27 8 2022
Statut: epublish

Résumé

Creating supersaturating drug delivery systems to overcome the poor aqueous solubility of active ingredients became a frequent choice for formulation scientists. Supersaturation as a solution phenomenon is, however, still challenging to understand, and therefore many recent publications focus on this topic. This work aimed to investigate and better understand the pH dependence of supersaturation of telmisartan (TEL) at a molecular level and find a connection between the physicochemical properties of the active pharmaceutical ingredient (API) and the ability to form supersaturated solutions of the API. Therefore, the main focus of the work was the pH-dependent thermodynamic and kinetic solubility of the model API, TEL. Based on kinetic solubility results, TEL was observed to form a supersaturated solution only in the pH range 3-8. The experimental thermodynamic solubility-pH profile shows a slight deviation from the theoretical Henderson-Hasselbalch curve, which indicates the presence of zwitterionic aggregates in the solution. Based on p

Identifiants

pubmed: 36015261
pii: pharmaceutics14081635
doi: 10.3390/pharmaceutics14081635
pmc: PMC9412861
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : János Bolyai Research Scholarship
ID : of the Hungarian Academy of Sciences
Organisme : Bolyai +
ID : New National Excellence Program of the Ministry for Innovation and Technology
Organisme : GITDA
ID : Governmental Information-Technology Development Agency, Hungary
Organisme : Ministry for Innovation and Technology
ID : ÚNKP-21-4
Organisme : National Research, Development, and Innovation Fund of Hungary
ID : TKP2021-EGA-02

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Auteurs

Szabina Kádár (S)

Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 3 Műegyetem rkp., 1111 Budapest, Hungary.

Dóra Csicsák (D)

Department of Pharmaceutical Chemistry, Semmelweis University, 9 Hőgyes Endre Street, 1092 Budapest, Hungary.

Petra Tőzsér (P)

Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 3 Műegyetem rkp., 1111 Budapest, Hungary.

Attila Farkas (A)

Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 3 Műegyetem rkp., 1111 Budapest, Hungary.

Tamás Pálla (T)

Department of Pharmaceutical Chemistry, Semmelweis University, 9 Hőgyes Endre Street, 1092 Budapest, Hungary.

Arash Mirzahosseini (A)

Department of Pharmaceutical Chemistry, Semmelweis University, 9 Hőgyes Endre Street, 1092 Budapest, Hungary.

Blanka Tóth (B)

Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111 Budapest, Hungary.

Gergő Tóth (G)

Department of Pharmaceutical Chemistry, Semmelweis University, 9 Hőgyes Endre Street, 1092 Budapest, Hungary.

Béla Fiser (B)

Institute of Chemistry, University of Miskolc, Miskolc-Egyetemváros, 3515 Miskolc, Hungary.
Ferenc Rákóczi II Transcarpathian Hungarian College of Higher Education, 90200 Berehove, Ukraine.

Péter Horváth (P)

Department of Pharmaceutical Chemistry, Semmelweis University, 9 Hőgyes Endre Street, 1092 Budapest, Hungary.

János Madarász (J)

Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111 Budapest, Hungary.

Alex Avdeef (A)

In-ADME Research, 1732 First Ave., #102, New York, NY 10128, USA.

Krisztina Takács-Novák (K)

Department of Pharmaceutical Chemistry, Semmelweis University, 9 Hőgyes Endre Street, 1092 Budapest, Hungary.

Bálint Sinkó (B)

Pion Inc., 10 Cook Street, Billerica, MA 01821, USA.

Enikő Borbás (E)

Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 3 Műegyetem rkp., 1111 Budapest, Hungary.

Gergely Völgyi (G)

Department of Pharmaceutical Chemistry, Semmelweis University, 9 Hőgyes Endre Street, 1092 Budapest, Hungary.

Classifications MeSH