Firocoxib nanocrystal towards to the treatment of veterinary osteoarthritis: development, physical-chemical characterization and in vitro safety evaluation

• Grant number: 21/12869-8
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: February 01, 2023
• End date: January 31, 2024
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Isabela Fernandes de Oliveira
• Grantee: Isabela Fernandes de Oliveira
• Company: LABORATORIOS DUPRAT LTDA (FILIAL)
• CNAE: Atividades veterinárias
• City: Descalvado
• Pesquisadores principais: Luiza de Oliveira Macedo ; Nádia Araci Bou-Chacra

Abstract

Osteoarthritis (OA), also known as arthrosis, is a joint disease with high incidence in human and veterinary health. In OA, there is a progressive loss of joint mechanical functions, overloading the subchondral bone. This state causes pain, lameness, difficulty in urinating and evacuating, walking or jogging, and irritability due to the high animal suffering. Among the available pharmacological treatments, firocoxib is well tolerated for dogs, penetrating the synovial fluid due to its high lipophilicity. However, this same feature reduces its bioavailability, which is 38%. The low bioavailability of firocoxib may result in less effective treatment, since its rapid onset of action is paramount for pain relief in OA. Considering that OA has no cure, adequate treatment is necessary for providing life quality for the dogs. Additionally, firocoxib has a high cost (R$ 600.00 to R$ 840.00 for 60 days), where long-term treatment becomes restricted to a small population portion. The nanocrystals strategy is a promising alternative to make the OA treatment more effective using firocoxib. In this approach, reducing the drug particle size to the nanoscale increases dissolution rate, saturation solubility, and mucoadhesiveness. It is a non-matrix system, composed only of drug and surfactant/stabilizer, increasing the cost-benefit of the final product. Miniaturized wet bead milling is a simple and economically viable nanocrystal preparation method with easy industry scale-up. For this innovative product to reach the market, technical-scientific challenges must be overcome. Such challenges refer to developing the final product with suitable physicochemical and biological features for the intended use. This project aims to develop and optimize the physicochemical features of firocoxib nanocrystals, evaluation of their preparation stability and in vitro safety. This proposal will allow the development of an effective, safe, and cost-effective drug formulation compared to the marketed product. (AU)