Synthesis, Characterization and Performance Evaluation of Aceclofenac-Urea Cocrystals

Abstract

Kumar et al.: Synthesis and Evaluation of Aceclofenac-Urea CocrystalsAceclofenac is one of the commonly used Nonsteroidal anti-inflammatory drugs representing the variety of therapeutic applications including management of pain, inflammation, rheumatoid arthritis, and osteoarthritis, etc. But very low solubility and dissolution rate of aceclofenac compromise its therapeutic effectiveness. So, current work focuses on the improvement of solubility and dissolution of aceclofenac by the cocrystal approach. Aceclofenac was screened with various coformers selected from Generally Recognized as Safe and Everything Added to Foods in the United States list using Molecular orbital package 2016 software to find out novel cocrystals of aceclofenac with improved biopharmaceutical properties. Novel cocrystals of aceclofenac with urea were synthesized by mechanochemical grinding method. The synthesized cocrystals (Aceclofenac-Urea neat grinding and Aceclofenac-Urea liquid assisted grinding) were characterized carefully by Differential scanning calorimetry, infrared spectroscopy and powder X-ray diffraction to verify the formation of the cocrystals. Pharmaceutically significant properties such as powder dissolution rate, solubility, and stability of the synthesized cocrystals were evaluated. Compared to aceclofenac, the synthesized cocrystals showed improved solubility and dissolution rate. The synthesized cocrystals were found to be non-hygroscopic and stable under ambient conditions.

Review: Potency of Amide Derivates as Co-Crystal Formers and Its Impact on the Physicochemical of Active Pharmaceutical Ingredients

“…Urea as a co-crystal-forming material has an amide group that can interact with carboxylic, pyridine, hydroxyl, and amide groups to form hydrogen bonds, thereby increasing the solubility, dissolution, or stability of pharmaceutical active ingredients, such as in aceclofenac-urea co-crystals (Kumar et al, 2020), catechin-urea co-crystals (Bakhtiar et al, 2015), ellagic-urea acid (Leng et al, 2021), bumetanid-urea co-crystal (Allu et al, 2020), and febuxostat-urea co-crystal (An et al, 2017). The formation of 5-fluorouracil co-crystals with urea coformers has succeeded in increasing the solubility of pure 5-fluorouracil 2.5-3 times and increasing its thermal stability (Cuadra et al, 2020).…”

Modulating the Drug Solubility of Aceclofenac by Design as Solid Lipid Particles: In Vitro/in Vivo Correlation

“…Many techniques have been developed to enhance the solubility of such drugs, but these techniques have many limitations, either for the cost or for the difficulty to apply the technique on the industrial scale [3]. New Pharmaceutical techniques are now developing to use conventional polymers and technologies to increase the solubility of class II drugs (Drugs with poor solubility) [4]. One of these technologies for improving the solubility of poorly soluble drugs involves the use of excipient-like lipid polymers [5].…”

“…ACF (fig. 1) is a class II drug as it is practically insoluble and its absorption is limited by its low dissolution rate [16]. This study aimed to investigate the role of lipid bases and their different blends in altering the dissolution rate of water-insoluble drugs to obtain release profiles for immediate and Eudragit RS100 coated sustained release formulations.…”

Pembentukan dan Karakterisasi Multikomponen Kristal Aseklofenak – Asam Suksinat Dengan Metode Solvent Drop Grinding.

“…Metode lain yang dapat digunakan untuk memperbaiki kelarutan dan laju disolusi adalah modifikasi fisika dengan pembentukan multikomponen kristal. Beberapa studi telah dilaporkan antara lain: kokristal aseklofenak dengan koformer asam salisilat dapat meningkatkan kelarutan aseklofenak menjadi 7 kali zat murninya [13], dan kokristal aseklofenak dengan koformer urea berhasil dibuat dengan menggunakan metode solvent drop grinding [2].…”