A comprehensive approach to transdermal drug delivery through the skin: Ibuprofen derivatives in semi-solid formulations

Abstract. This article presents a comprehensive study on the formulation and evaluation of pharmaceutical emulsions for topical drug delivery. The research focused on emulsions containing ibuprofen and its derivatives (sodium and L-lysine propyl ester salts), investigating their solubility, consistency, stability, and skin permeation. The study offers valuable insights into the development of effective pharmaceutical products. Background. Transdermal and topical drug delivery is a promising approach for the treatment of various medical conditions. Pharmaceutical emulsions provide an ideal platform for delivering active substances through the skin. The selection of emulsion ingredients, consistency, and stability play a critical role in determining the suitability of these formulations. Aim of the study. The primary aim of this study was to formulate and evaluate pharmaceutical emulsions containing ibuprofen and other active substances. Key objectives included assessing solubility, consistency, stability, and skin permeation characteristics of the emulsions. The study aimed to provide insights into the development of effective topical drug delivery systems. Material and methods. Solubility tests were conducted to select suitable emulsion ingredients. Various emulsions were prepared with different water-to-oil phase ratios. Rheology modifiers were added to enhance consistency. Quality control assessments were performed, including uniformity, consistency, stability, density, viscosity, and particle size analysis. The release of active substances from the formulations and their penetration and accumulation in the skin were determined. Results. The results revealed variations in viscosity, consistency, and stability among different formulations. Emulsion-based preparations demonstrated the highest accumulation of active substances in the skin, with formulation F1 (5294.617 μg/g skin) exhibiting the most promising results. The highest release of ibuprofen was observed from the formulation based on Celugel with the addition of [LysOPr][IBU] (F6) - approximately 7750 μg IBU/cm2, and the highest penetration of the active substance was obtained for the emulsion with the addition of IBU∙Na (F2) - 3300 μg IBU/cm2 after 24 hours of testing. Conclusion. This comprehensive study on pharmaceutical emulsions for topical drug delivery provides critical insights into the formulation and evaluation of cosmetic and pharmaceutical products. The findings highlight the importance of ingredient selection, consistency, and stability in the development of effective emulsion-based formulations. Furthermore, the study suggests that emulsion-based preparations have potential for topical applications, especially for more hydrophilic active substances. Future research can build on these results to enhance drug delivery systems and improve patient outcomes

Synthesis of Epoxy Methacrylate Resin and Coatings Preparation by Cationic and Radical Photocrosslinking

This work involves the synthesis of hybrid oligomers based on the epoxy methacrylate resin. The EA resin was obtained by the modification of industrial-grade bisphenol A-based epoxy resin and methacrylic acid has been synthesized in order to develop multifunctional resins comprising both epoxide group and reactive, terminal unsaturation. Owing to the presence of both epoxy and double carbon–carbon pendant groups, the reaction product exhibits photocrosslinking via two distinct mechanisms: (i) cationic ring-opening polymerization and (ii) free radical polymerization. Monitoring of EA synthesis reactions over time using PAVs, MAAC and NV parameters, and the FT-IR method reveals that esterification reactions proceed faster at the start, exhibiting over 40% of conversion within the initial 60 min, which can be associated with a relatively high concentration of reactive sites and low viscosity of the reaction mixture at the initial reaction stage. With the further increase in the reaction time, the reaction rate tends to decrease. The control of the EA synthesis process can guide how to adjust reactions to obtain EAs with desired characteristics. Based on obtained values, one can state that the optimum synthesis time of about 4–5 h should be adopted to prepare EAs having both epoxy groups and unsaturated double bonds. The structure of the obtained EA was confirmed by FT-IR and NMR methods, as well as the determination of partial acid value and epoxy equivalent. Samples at various stages of synthesis were cured with UV radiation in order to study the kinetics of the process according to cationic and radical polymerization determined via photo-differential scanning calorimetry (photo-DSC) and real-time infrared spectroscopy (RT-IR) and then the properties of the cured coatings were tested. It turned out that the cationic polymerization was slower with a lower conversion of the photoreactive groups, as compared to the radical polymerization. All the obtained EA coatings were characterized by good properties of cured coatings and can be successfully used in the coating-forming sector

Anhydride-Cured Epoxy Powder Coatings from Natural-Origin Resins, Hardeners, and Fillers

Carbon-neutral policy and technological race on the powder coatings market force to develop more advanced, safer, cheaper, and naturally sourced products. To meet the market needs, powder coating compositions and coatings were prepared from safe and natural-origin hardeners, resins, and fillers prepared from rosin, bio-diols, bio-epichlorohydrin, and halloysite, to investigate their thermal, mechanical, and functional properties in comparison with petroleum-based references: cross-linking behavior, glass transition temperature, thermal stability, hardness, cupping resistance, adhesion, chemical resistance, gloss, color, and anti-corrosive behavior in salt chamber. As a result, compositions containing up to 83 wt.% of natural resources, and showing comparable or better properties, as compared to references, were successfully prepared. Their application includes binders for future ecological powder paints for demanding protection of steel substrates

Composition and Properties of Protective Coatings Made of Biologically-Derived Polyester Reactive Binder

Biologically derived polymers are a very attractive subject for investigation, due to the strict pro-ecological requirements imposed by developed countries, including zero-waste and zero-carbon policies as well as volatile organic compound (VOC) limits. Synthesis of biologically-derived polyesters from natural rosin and bio-diols, showing softening temperatures suitable for application in VOC-free paints and varnishes, was performed to create a desired, future commercial product, that meet the aforementioned requirements regarding VOC and elimination of petroleum-based raw materials. Prepared polymers were used in the formulation of coating materials whose properties: cross-linking behavior, glass transition temperature, thermal stability, storage modulus, hardness, cupping resistance, adhesion, chemical resistance, gloss, haze, color, and anti-corrosive behavior in the salt chamber were investigated and discussed. As a result, coatings with prepared bio-polyesters contained over 80 wt.% of natural resources and showed competitive/better properties than petroleum-based references. They can be applied in the prototyping of “green” powder paints for the protection of steel substrates from corrosion and aggressive solvents

Farby ochronne z surowców naturalnych : kompozycja i właściwości

Climate changes and increasing cost of non-renewable resources cause the growing interest in technical materials prepared from natural resources. To meet this interest, prototype paints from rosin and bio-diols derivatives, and also halloysite, were formulated to check their thermal, mechanical, visual and functional properties, as protective coatings of steel. Prepared materials contained ca. 75 wt % of natural resources and exhibited considerably better corrosion protection, thermal stability, and also higher glass transition temperatures and hardness, than a commercial petroleum-based reference sample. The other parameters: cross-linking behavior, color, gloss, cupping resistance, adhesion and chemical resistance were within the range that is acceptable for potential users.Zmiany klimatyczne i rosnące koszty surowców nieodnawialnych powodują zwiększenie zainteresowania materiałami o znaczeniu technicznym, otrzymywanymi z surowców pochodzenia naturalnego. Wychodząc naprzeciw temu zainteresowaniu, opracowano prototypowe farby z pochodnych kalafonii i bio-dioli oraz haloizytu w celu sprawdzenia ich właściwości termicznych, mechanicznych, wizualnych i funkcjonalnych, jako powłok ochronnych dla stali. Przygotowane materiały zawierały ok. 75% mas. surowców naturalnych i wykazywały znacznie lepszą ochronę przed korozją, stabilność termiczną, a także wyższe temperatury zeszklenia i twardość niż komercyjna próbka referencyjna otrzymana z surowców ropopochodnych. Pozostałe parametry: kinetyka sieciowania, kolor, połysk, tłoczność, adhezja i odporność chemiczna, mieściły się w akceptowalnym zakresie dla potencjalnych użytkowników

Impact of the Chemical Structure of Photoreactive Urethane (Meth)Acrylates with Various (Meth)Acrylate Groups and Built-In Diels–Alder Reaction Adducts on the UV-Curing Process and Self-Healing Properties

A series of UV-curable urethane (meth)acrylates were obtained by copolymerization of the Diels–Alder adduct (HODA), isophorone diisocyanate, PEG1000, and various hydroxy (meth)acrylates. The aim of the present work was to determine the influence of the chemical structure of the introduced (meth)acrylic groups, i.e., hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxyethyl methacrylate, and hydroxypropyl methacrylate, on the UV-curing process and self-healing properties of cured coatings. The chemical structure of prepolymers was characterized by FTIR and NMR spectroscopy, whereas the UV-curing process was monitored in real time using FTIR and photo-DSC. In turn, the self-healing properties were characterized in relation to the thermally reversible mechanism, which was tested using the following methods: an FTIR spectroscope equipped with a heating attachment; DSC and TG apparatus; and an optical microscope equipped with a stage with programmable heating. The result of comprehensive research on the self-healing of photocurable coatings in the context of the presence of various photoreactive groups and the course of the curing process allows one to control the self-healing process by reducing the effective healing temperature. The self-healing properties, taken together with the fast UV curing of the coatings and excellent properties of cured coatings, make the material attractive for a variety of applications, in particular in cases where coatings are not repaired, e.g., for economic reasons or when it is not possible, such as in flexible electronic screens, car paint film, and aircraft interior finishes

Isopropyl Amino Acid Esters Ionic Liquids as Vehicles for Non-Steroidal Anti-Inflammatory Drugs in Potential Topical Drug Delivery Systems with Antimicrobial Activity

New derivatives of non-steroidal anti-inflammatory drugs were synthesized via conjugation with L-amino acid isopropyl esters. The characteristics of the physicochemical properties of the obtained pharmaceutically active ionic liquids were determined. It has been shown how the incorporation of various L-amino acid esters as an ion pair affects the properties of the parent drug. Moreover, the antimicrobial activity of the obtained compounds was evaluated. The proposed structural modifications of commonly used drugs indicate great potential for use in topical and transdermal preparations

Synthesis of Hybrid Epoxy Methacrylate Resin Based on Diglycidyl Ethers and Coatings Preparation via Cationic and Free-Radical Photopolymerization

A series of difunctional epoxy methacrylate resins (EAs) containing at least one epoxy and at least one methacrylate group were synthesized by means of an addition reaction between epoxy-terminated diglycidyl ethers and methacrylic acid. In order to investigate the impact of polymer architecture on the course of addition reactions and further coating properties, several different types of diglycidyl ethers, i.e., linear, containing aliphatic or aromatic rings, with a short or polymeric backbone, were employed in the synthesis. The carboxyl–epoxide addition esterification reactions have been found to, in a relatively straightforward manner, control the extent of acrylation depending on the substrate feed ratio and reaction time. The structure of obtained pre-polymers was evaluated by FT-IR and NMR methods. At the same time, the extent of addition reactions was validated via quantitative analysis, including non-volatile matter content (NV), acid value (PAVs), and epoxy equivalent value (EE) analysis. The modification was carried out in a manner likely to create a compound with one epoxy and one carbon–carbon pendant group. Hence, due to the presence of both functionalities, it is possible to crosslink compositions based on synthesized EAs via two distinct mechanisms: (i) cationic polymerization or (ii) free-radical polymerization. Synthesized epoxy methacrylate pre-polymers were further employed for use in formulate photocurable coating compositions by the cationic or radical process. Furthermore, the photopolymerization behavior and properties of cured coatings were explored regarding some structural factors and parameters. The investigated polymeric materials cure in a short time to obtain coatings with good properties, which is why they can be successfully used to produce protective and decorative coatings for many industries

Exploring Alkyl Ester Salts of L-Amino Acid Derivatives of Ibuprofen: Physicochemical Characterization and Transdermal Potential

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

Novel Naproxen Salts with Increased Skin Permeability

The paper presents the synthesis, full identification, and characterization of new salts-L-proline alkyl ester naproxenates [ProOR][NAP], where R was a chain from ethyl to butyl (including isopropyl). All obtained compounds were characterized by Nuclear Magnetic Resonance (NMR), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffractometry (XRD), and in vitro dissolution studies. The specific rotation, phase transition temperatures (melting point), and thermal stability were also determined. In addition, their lipophilicity, permeability, and accumulation in pigskin were determined. Finally, toxicity against mouse L929 fibroblast cells was tested. The obtained naproxen derivatives showed improved solubility and higher absorption of drug molecules by biological membranes. Their lipophilicity was lower and increased with the increase in the alkyl chain of the ester. The derivative with isopropyl ester had the best permeability through pigskin. The use of L-proline isopropyl ester naproxenate increased the permeation of naproxen through the skin almost four-fold. It was also shown that the increase in permeability is not associated with additional risk: all compounds had a similar effect on cell viability as the parent naproxen