Development of phytotherapy products based on curcuminoids as anti-inflammatory agents for veterinary applications

Abstract

In Brazil, as in many countries around the world, the veterinary market is growing every year, as well as the appeal to natural and sustainable products such as phytotherapics. Only 1% of the phytotherapy market in Brazil is focused on the veterinary segment, but the sector grows around 25% a year, surpassing any other. This project fits within this branch, proposing the curcuminoids, actives found in a plant popularly known an açafrão da terra, or Curcuma longa L, as a phytotherapic solution. Açafrão derivatives have several therapeutic properties proven in the scientific literature, and in addition, they have great commercial potential as anti-inflammatory for animals, including pet lines, medium and large sizes. Despite this potential, there is a limitation to be overcome: the solubility of curcumin. This is a determinant factor for its bioavailability when administered orally, because curcuminoids belong to Class II of the Biopharmaceutical Classification System, that is, low solubility and high oral permeability. In Phase 1 of this PIPE, the results obtained confirmed the hypothesis that microparticles of solid dispersion of curcuminoids obtained by spray congealing would increase the solubility of these actives and cause an improvement in their performance as an oral veterinary anti-inflammatory. Therefore, the feasibility of the concept, the mission of Phase 1, was duly accomplished, as can be seen in its technical-scientific report. In Phase 2, the project aims to extend the work with: 1) the study of new variables in the production process of microparticles by spray congealing, aiming at their optimization, using multivariate analysis tools (DOE), at increasing the solubility, dissolution rate, cost analysis, stability, in vitro anti-inflammatory activity; 2) complete cytotoxicity studies with more models; 3) complete in vivo anti-inflammatory dose studies (in rats) reconciling with toxicity studies; 4) prepare final solid forms (pet drugs in "palatable" form) containing the microparticles; 5) evaluate the palatability of these forms; 6) evaluate the stability (shelf life) of these forms; 7) preparing semi-solid final forms (liquid crystals) containing the microparticles for its topical application; 8) perform clinical trials (third party) on pet animals such as dogs and cats with both forms (palatable and topical). In Phase 2 of this PIPE it is also intended to evaluate the possibility of applying the microparticles in systems with antimicrobial activity for a new application that would be for the preventive and prophylactic treatment of bovine mastitis by: 1) evaluation Of Minimum Inhibitory Concentration (MIC) of microparticles in pathogenic microorganisms that cause mastitis; 2) preparing pharmaceutical forms for topical application of microparticles (liquid monoolein crystals), evaluating their physicochemical and pharmacotechnical properties; 3) evaluation of the anti-inflammatory and antimicrobial activity of this formulation in vitro. (AU)