Exploring Alkyl Ester Salts of L-Amino Acid Derivatives of Ibuprofen: Physicochemical Characterization and Transdermal Potential
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Published:2023-11-10
Issue:22
Volume:28
Page:7523
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ISSN:1420-3049
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Container-title:Molecules
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language:en
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Short-container-title:Molecules
Author:
Witkowski Kordian1, Nowak Anna2ORCID, Duchnik Wiktoria2ORCID, Kucharski Łukasz2ORCID, Struk Łukasz3ORCID, Ossowicz-Rupniewska Paula1ORCID
Affiliation:
1. Department of Chemical Organic Technology and Polymeric Materials, Faculty of Chemical Technology and Engineering, West Pomeranian University of Technology in Szczecin, Piastów Ave. 42, 71-065 Szczecin, Poland 2. Department of Cosmetic and Pharmaceutical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich Ave. 72, 70-111 Szczecin, Poland 3. Department of Organic and Physical Chemistry, Faculty of Chemical Technology and Engineering, West Pomeranian University of Technology in Szczecin, Al. Piastów 42, 71-065 Szczecin, Poland
Abstract
This research presents novel ibuprofen derivatives in the form of alkyl ester salts of L-amino acids with potential analgesic, anti-inflammatory, and antipyretic properties for potential use in transdermal therapeutic systems. New derivatives of (RS)-2-[4-(2-methylpropyl)phenyl]propionic acid were synthesized using hydrochlorides of alkyl esters (ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, and pentyl) of L-glutamine. These were further transformed into alkyl esters of L-amino acid ibuprofenates through neutralization and protonation reactions. Characterization involved spectroscopic methods, including nuclear magnetic resonance and Fourier-transform infrared spectroscopy. Various physicochemical properties were investigated, such as UV–Vis spectroscopy, polarimetric analysis, thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, water solubility, octanol/water partition coefficient, and permeability through pig skin using Franz diffusion cells. The research confirmed the ionic structure of the obtained hydrochlorides of alkyl esters of L-amino acids and ibuprofenates of alkyl esters of L-glutamic acid. It revealed significant correlations between ester chain length and thermal stability, crystallinity, phase transition temperatures, lipophilicity, water solubility, skin permeability, and skin accumulation of these compounds. Compared to the parent ibuprofen, the synthesized derivatives exhibited higher water solubility, lower lipophilicity, and enhanced skin permeability. This study introduces promising ibuprofen derivatives with improved physicochemical properties, highlighting their potential for transdermal therapeutic applications. The findings shed light on the structure–activity relationships of these derivatives, offering insights into their enhanced solubility and skin permeation, which could lead to more effective topical treatments for pain and inflammation.
Funder
National Centre for Research and Development
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
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