Abstract
Most nonsteroidal anti-inflammatory drugs (NSAIDs) present poor aqueous solubility, impairing their efficiency in physiological media. In this context, Low Transition Temperature Mixtures (LTTMs) are a promising platform to overcome drugs’ poor solubility, forming therapeutic liquid formulations. In this work, the LTTMs of citric acid:L-arginine:water (C:A:W) and glycerol:sorbitol (G:S) were studied in terms of their features and assessed in terms of their ability to increase the solubility of six NSAIDs in physiological media. The physicochemical properties of LTTMs were characterized by state-of-art techniques commonly used for these systems. The cytotoxicity of G:S was also evaluated in L929 mouse fibroblasts and the viscosity, polarity, and pH properties of the studied mixtures were related to the solubility of NSAIDs. The pH and polarity were the parameters that most influenced the drugs’ solubility. Ibuprofen, naproxen, ketoprofen, indomethacin, and flurbiprofen did not present any solubility improvement in the formulations tested. However, concentrated mixtures of C:A:W or G:S in the physiologic-mimicked media (PBS) rendered a celecoxib solubility 4 and 5 times higher than PBS, respectively. These therapeutic liquid formulations of celecoxib in C:A:W or G:S can be a promising tool to increase celecoxib’s therapeutic efficiency in local applications.
Highlights
Nonsteroidal anti-inflammatory drugs (NSAIDs) are anti-inflammatory, antipyretic, and analgesic medicines commonly used worldwide for the symptomatic relief of headaches, strains, sprains, viral infections such as the flu or corona, arthritis, and other cases of pain, fever, and/or inflammation [1]
The G:S and C:A:W systems were chosen based on their favourable properties towards osteoarthritis (OA) treatment, which was chosen as a model application
G:S and C:A:W mixtures were explored in terms of their properties and ability to improve NSAIDs’ solubility in therapeutical applications
Summary
Nonsteroidal anti-inflammatory drugs (NSAIDs) are anti-inflammatory, antipyretic, and analgesic medicines commonly used worldwide for the symptomatic relief of headaches, strains, sprains, viral infections such as the flu or corona, arthritis, and other cases of pain, fever, and/or inflammation [1]. Despite being regarded as generally safe, most NSAIDs require the intake of higher amounts than the therapeutic dose due to their general low solubility in the physiological media [2]. These drugs are associated to gastrointestinal, cardiovascular, and other adverse effects potentiated by high doses and prolonged consumption [1]. In the case of chronic diseases like osteoarthritis, this is specially concerning as this is the most administered treatment for the persistent symptoms of pain and inflammation [3,4,5] In this context, biocompatible formulations that improve the efficiency and safety of marketed drugs, while avoiding the long-term development of new drugs associated to the regulatory entities, are of great importance.
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