Ferulic acid (FA) has been widely used in the pharmaceutical and cosmetics industry due to its, inter alia, antioxidant, antiaging and anti-inflammatory effects This compound added to cosmetic preparations can protect skin because of its photoprotective activity. However, the usefulness of FA as a therapeutic agent is limited due to its low solubility and bioavailability. The paper presents the synthesis, identification, and physicochemical properties of new FA derivatives with propyl esters of three amino acids, glycine (GPr[FA]), L-leucine (LPr[FA]), and L-proline (PPr[FA]). The NMR and FTIR spectroscopy, DSC, and TG analysis were used as analytical methods. Moreover, water solubility of the new conjugates was compared with the parent acid. Both ferulic acid and its conjugates were introduced into hydrogel and emulsion, and the resulting formulations were evaluated for stability. Additionally, in vitro penetration of all studied compounds from both formulations and for comparative purposes using Franz diffusion cells was evaluated from the solution in 70% (v/v) ethanol. Finally, cytotoxicity against murine fibroblasts L929 was tested. All of the analyzed compounds permeated pig skin and accumulated in it. LPr[FA] and PPr[FA] were characterized by much better permeability compared to the parent ferulic acid. Additionally, it was shown that all the analyzed derivatives are characterized by high antioxidant activity and lack of cytotoxicity. Therefore, they can be considered as an interesting alternative to be applied in dermatologic and cosmetic preparations.

Modifications of (RS)-2-[4-(2-methylpropyl)phenyl] propanoic acid with amino acid isopropyl esters were synthesised using different methods via a common intermediate. The main reaction was the esterification of the carboxyl group of amino acids with isopropanol and chlorination of the amino group of the amino acid, followed by an exchange or neutralisation reaction and protonation. All of the proposed methods were very efficient, and the compounds obtained have great potential to be more effective drugs with increased skin permeability compared with ibuprofen. In addition, it was shown how the introduction of a modification in the form of an ion pair affects the properties of the obtained compound.

This study aimed to evaluate the effect of chemical modifications of the structure of active compounds on the skin permeation and accumulation of ibuprofen [IBU] from the acrylic pressure-sensitive adhesive used as a drug-in-adhesives matrix type transdermal patch. The active substances tested were ibuprofen salts obtained by pairing the ibuprofen anion with organic cations, such as amino acid isopropyl esters. The structural modification of ibuprofen tested were Ibuprofen sodium salt, [GlyOiPr][IBU], [AlaOiPr][IBU], [ValOiPr][IBU], [SerOiPr][IBU], [ThrOiPr][IBU], [(AspOiPr)₂][IBU], [LysOiPr][IBU], [LysOiPr][IBU]₂, [PheOiPr][IBU], and [ProOiPr][IBU]. For comparison, the penetration of unmodified ibuprofen and commercially available patches was also investigated. Thus, twelve transdermal patches with new drug modifications have been developed whose adhesive carrier is an acrylate copolymer. The obtained patches were characterized for their adhesive properties and tested for permeability of the active substance. Our results show that the obtained ibuprofen patches demonstrate similar permeability to commercial patches compared to those with structural modifications of ibuprofen. However, these modified patches show an increased drug permeability of 2.3 to even 6.4 times greater than unmodified ibuprofen. Increasing the permeability of the active substance and properties such as adhesion, cohesion, and tack make the obtained patches an excellent alternative to commercial patches containing ibuprofen.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain relief and inflammation management, but there are challenges related to poor solubility and bioavailability. We explored modifications of ibuprofen (IBU) by forming ionic pairs using amino acid alkyl esters to enhance solubility without compromising the ability to inhibit cyclooxygenase (COX)-1 and COX-2). We comprehensively evaluated the pharmacological properties of the IBU derivatives, focusing on antioxidant activity (based on the ability to scavenge DPPH and ABTS), biocompatibility (using human dermal fibroblasts), and COX inhibitory potential. The antioxidant activity assays significantly enhanced DPPH scavenging activity for several IBU derivatives, particularly [l-SerOiPr][IBU], suggesting potential therapeutic benefits. There was enhanced cell viability with select derivatives, indicating possible stimulatory effects on cellular proliferation. Finally, predominant COX-1 inhibition across derivatives was consistent with IBU’s profile. This study provides insights into the pharmacological properties of IBU amino acid derivatives, highlighting their potential as therapeutic agents. Further exploration into structure–activity relationships and in vivo efficacy warranted to advance these derivatives toward clinical applications, offering prospects for novel NSAIDs with enhanced efficacy and reduced side effects.

Water pollution caused by anthropogenic activity is a huge environmental problem. Huge amounts of consumed medicinal substances cause them to get into the environment. Non-steroidal anti-inflammatory drugs, including ibuprofen, are one of the most popular drugs in the world. This article presents the biodegradation of ibuprofen and isopropyl ester salts of various amino acids. Twelve ibuprofen isopropyl esters of L-amino acids were used in the research. The obtained derivatives may be a safer and more effective alternative to ibuprofen. Biodegradation tests were carried out using activated sludge. Sewage sludge was obtained from the local sewage treatment plant in Szczecin "Pomorzany". Ibuprofen derivatives, ibuprofenates of isopropyl amino acid esters, were used for the tests. It was checked how the type of structural modification of ibuprofen affects the biodegradation of the drug used. In this publication, it was verified how the type of amino acid affects biodegradation. Our evaluation of the biodegradation of ibuprofen derivatives by bacterial cultures revealed that six compounds are attractive carbon and energy sources for the active material utilized. These compounds were readily biodegradable within 28 days. There were no straightforward relationships between the structure, properties, and biodegradability of the obtained derivativesWater pollution caused by anthropogenic activity is a huge environmental problem. Huge amounts of consumed medicinal substances cause them to get into the environment. Non-steroidal anti-inflammatory drugs, including ibuprofen, are one of the most popular drugs in the world. This article presents the biodegradation of ibuprofen and isopropyl ester salts of various amino acids. Twelve ibuprofen isopropyl esters of L-amino acids were used in the research. The obtained derivatives may be a safer and more effective alternative to ibuprofen. Biodegradation tests were carried out using activated sludge. Sewage sludge was obtained from the local sewage treatment plant in Szczecin "Pomorzany". Ibuprofen derivatives, ibuprofenates of isopropyl amino acid esters, were used for the tests. It was checked how the type of structural modification of ibuprofen affects the biodegradation of the drug used. In this publication, it was verified how the type of amino acid affects biodegradation. Our evaluation of the biodegradation of ibuprofen derivatives by bacterial cultures revealed that six compounds are attractive carbon and energy sources for the active material utilized. These compounds were readily biodegradable within 28 days. There were no straightforward relationships between the structure, properties, and biodegradability of the obtained derivatives

The compositions based on Pentravan^® vehicle were prepared with (S)-naproxen, and its salt —(S)-naproxenate of L-prolinium isopropyl ester as active pharmaceutical ingredients, and two penetration enhancers from the group of sensates—menthol and Capsicum Tincture. Thermophysical properties of the mixtures of each naproxen form with enhancers were determined by DSC method. The stability of the prepared compositions after one- and three-month storage and the rheological properties were investigated. The permeation of active ingredients through the human skin was evaluated based on the in vitro study in Franz diffusion cells using the prepared compositions with each naproxen form. Increase in the permeability of the naproxen salt, especially in the presence of Capsicum Tincture, provides much faster and greater penetration of the skin by the drug. It seems to be promising the use of the developed composition in the form of pain relief and anti-inflammatory creams, occlusive compresses or topical patches. Moreover, the developed compositions can be crucial for the topical compositions made in compounding pharmacies by physicians’ recipes in individual pain pharmacotherapy.