Therapeutic Liquid Formulations Based on Low Transition Temperature Mixtures for the Incorporation of Anti-Inflammatory Drugs

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.

Role of crosslinkers on the properties of bio‐based wood adhesives

“…The increase in T g might be related to an increased crosslinking, which reduces the flexibility of the polymer chain indicating stronger material. Moreover, in the samples containing SR as a crosslinker, a second endothermic event occurred at ~95°C which could be due to unreacted SR 46,47 …”

“…The increase in T g might be related to an increased crosslinking, which reduces the flexibility of the polymer chain indicating stronger material. Moreover, in the samples containing SR as a crosslinker, a second endothermic event occurred at $95 C which could be due to unreacted SR. 46,47 3.7 | Gel content and swelling Figure 9 represents the swelling and gel content values of the adhesives cured at room temperature in water and toluene. Water has shown less effect on the samples' properties in terms of gelling and swelling.…”

Experimental and Machine-Learning-Assisted Design of Pharmaceutically Acceptable Deep Eutectic Solvents for the Solubility Improvement of Non-Selective COX Inhibitors Ibuprofen and Ketoprofen

“…Despite the fact that the extent of their environmental friendliness has recently become a topic of debate [74][75][76][77], DESs showcase remarkable potential across various domains of pharmaceutical applications, including drug synthesis, formulation, and extraction processes [78][79][80][81][82][83][84][85][86][87][88]. Noteworthily, DESs have been shown to be effective solubilizers of ibuprofen [89,90] and ketoprofen [91]. As it can be seen, a substantial dataset has emerged, which serves as an intriguing starting point for modeling the solubilization properties of both examined active substances.…”

Characterizing the Solvation Characteristics of Deep Eutectic Solvents Composed of Active Pharmaceutical Ingredients as a Hydrogen Bond Donor and/or Acceptor

“…Characterizing the solvation interactions (i.e., dipolarity/polarizability, dispersion, hydrogen-bonding, n –π, and π–π interactions) is of utmost importance to fully exploit the designer aspects of API DESs where the API can be employed as HBA, HBD, or HBA and HBD and to understand the complex interplay between the HBA and HBD in API DESs. Several studies have reported the preparation and applications of API DESs using different APIs such as aspirin, ibuprofen, lidocaine, and prilocaine with excipients (molecules that deliver the active ingredient to active site) such as carboxylic acids, long-chain alcohols, and choline chloride. ,, However, studies that evaluate their polarity and intermolecular solvation interactions are very limited. − Single polarity scales such as Reichardt’s polarity index and Nile red polarity scale have been used for DESs. − Kamlet–Taft parameters have also been employed to separately quantify the dipolarity/polarizability (π*), hydrogen-bond-accepting ability (β), and hydrogen-bond-donating ability ( a ) . Saha et al.…”