Utilizing the allyl-terminated copolymer methoxy(poly(ethylene glycol))-block-poly(jasmine lactone) in the development of amorphous solid dispersions: A comparative study of functionalized and non-functionalized polymer.

Autor: Di R; University of Copenhagen, Faculty of Health and Medical Sciences, Department of Pharmacy, Copenhagen, Denmark. Electronic address: rong.di@sund.ku.dk., Bansal KK; Åbo Akademi University, Faculty of Science and Engineering, Pharmaceutical Sciences Laboratory, Turku, Finland. Electronic address: kuldeep.bansal@abo.fi., Rosenholm JM; Åbo Akademi University, Faculty of Science and Engineering, Pharmaceutical Sciences Laboratory, Turku, Finland. Electronic address: jessica.rosenholm@abo.fi., Grohganz H; University of Copenhagen, Faculty of Health and Medical Sciences, Department of Pharmacy, Copenhagen, Denmark. Electronic address: holger.grohganz@sund.ku.dk., Rades T; University of Copenhagen, Faculty of Health and Medical Sciences, Department of Pharmacy, Copenhagen, Denmark. Electronic address: thomas.rades@sund.ku.dk.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 May 25; Vol. 657, pp. 124175. Date of Electronic Publication: 2024 Apr 27.
DOI: 10.1016/j.ijpharm.2024.124175
Abstrakt: Molecular interactions are crucial to stabilize amorphous drugs in amorphous solid dispersions (ASDs). Most polymers, however, have only a limited ability to form strong molecular interactions with drugs. Polymers tailored to fit the physicochemical properties of the drug molecule to be incorporated, for instance by allowing the incorporation of specific functional groups, would be highly sought-for in this regard. For this purpose, the novel allyl-terminated polymer methoxy(polyethylene glycol)-block-poly(jasmine lactone) (mPEG-b-PJL) has been synthesized and functionalized to potentially enhance specific drug-polymer interactions. This study investigated the use of mPEG-b-PJL in ASDs, using carvedilol (CAR), a weakly basic model drug. The findings revealed that the acidic functionalized form of the polymer (mPEG-b-PJL-COOH) indeed established stronger molecular interactions with CAR compared to its non-functionalized counterpart mPEG-b-PJL. Evaluations on polymer effectiveness in forming ASDs demonstrated that mPEG-b-PJL-COOH outperformed its non-functionalized counterpart in miscibility, drug loading ability, and stability, inferred from reduced molecular mobility. However, dissolution tests indicated that ASDs with mPEG-b-PJL-COOH did not significantly improve the dissolution behaviour compared to amorphous CAR alone, despite potential solubility enhancement through micelle formation. Overall, this study confirms the potential of functionalized polymers in ASD formulations, while the challenge of improving dissolution performance in these ASDs remains an area of further development.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of Generative AI and AI-assisted technologies in the writing process During the preparation of this work R.D. used ChatGPT and Grammarly in order to improve the readability and language of the paper. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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