Desenvolvimento de complexos de inclusão e dispersões sólidas da alfa, beta amirina isolada a partir do protium heptaphyllum

Abstract

α, β amyrin (ABAM) is a natural mixture of triterpenes pentacyclis which has various biological activities, including the anti-inflammatory effect. Are isolated from the species in the family Burseraceae, in which the species Protium heptaphyllum is more commonly found in the brazilian Amazon. The inclusion complexes formation (IC) with the cyclodextrin (CD) and solid dispersions (SD) with hydrophilic polymers have been applied as alternatives to solve some limitations that new chemical entities (NCE) have in common, mainly the low solubility in aqueous environments. So, the objective of this work was to develop IC's the ABAM (ABAM) with β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD) and SD with the hidroximetilcelulose (HPMC), polyethylene glycol (PEG 6000) and polyvinylpyrrolidone (PVP-30 k). Initially, for the IC, computational theoretical studies were carried out in which interaction energies were calculated between the βCD and the ABAM and HPβCD and ABAM. Then, the IC's have been developed with βCD and HPβCD by mixing physical methods (MF) and kneading (KND). The physical and chemical characterization of IC's using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), x-ray diffraction (DRX), thermogravimetric analysis (TG) and differential scanning calorimetry (DSC). The DS were obtained through the MF, KND and RE with HPMC, PEG and the PVP. Held the same characterization techniques that were held for the IC. Beyond characterization to the DS, the anti-inflammatory activity in vitro and were compared with respect to their anti-inflammatory activities with the ABAM. The characterization studies showed the formation of CI between the ABAM and the CD and the formation of solid dispersions between the ABAM and hydrophilic polymers. In the activity of DS, it was found that comparing the effect, the same dose of ABAM and same dose of the DS, the DS as the ABAM had anti-inflammatory activity on macrophages activated by LPS. Therefore, the DS and CI with ABAM are effective alternatives to modify their characteristics, improving properties that may interfere in a future therapeutic formulation.