Solid dispersion of ursolic acid in Gelucire 50/13: a strategy to enhance drug release and trypanocidal activity.
Solid dispersions (SDs) are an approach to increasing the water solubility and bioavailability of lipophilic drugs such as ursolic acid (UA), a triterpenoid with trypanocidal activity. In this work, Gelucire 50/13, a surfactant compound with permeability-enhancing properties, and silicon dioxide, a drying adjuvant, were employed to produce SDs with UA. SDs and physical mixtures (PMs) in different drug/carrier ratios were characterized and compared using differential scanning calorimetry, hot stage microscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), particle size, water solubility values, and dissolution profiles. Moreover, LLC-MK2 fibroblast cytotoxicity and trypanocidal activity evaluation were performed to determine the potential of SD as a strategy to improve UA efficacy against Chagas disease. The results demonstrated the conversion of UA from the crystalline to the amorphous state through XRD. FTIR experiments provided evidence of intermolecular interactions among the drug and carriers through carbonyl peak broadening in the SDs. These findings helped explain the enhancement of water solubility from 75.98 μg/mL in PMs to 293.43 μg/mL in SDs and the faster drug release into aqueous media compared with pure UA or PMs, which was maintained after 6 months at room temperature. Importantly, improved SD dissolution was accompanied by higher UA activity against trypomastigote forms of Trypanosoma cruzi, but not against mammalian fibroblasts, enhancing the potential of UA for Chagas disease treatment.
Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Avenida do Café s/n, 14040-903, Ribeirão Preto, São Paulo, Brazil.
Josimar
J
de Oliveira Eloy
Juliana
J
Saraiva
Sergio
S
de Albuquerque
Juliana Maldonado
JM
Marchetti
D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D014355:Chagas Disease / Q000188:drug therapy; D004337:Drug Carriers / Q000737:chemistry; D005223:Fats / Q000737:chemistry*; D005347:Fibroblasts / Q000187:drug effects; D009821:Oils / Q000737:chemistry*; D010316:Particle Size; D010539:Permeability; D012822:Silicon Dioxide / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013501:Surface-Active Agents / Q000737:chemistry; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods; D000097245:Ursolic Acid
D004337:Drug Carriers; D005223:Fats; D009821:Oils; D012822:Silicon Dioxide; D013501:Surface-Active Agents; D014315:Triterpenes; D014344:Trypanocidal Agents; D014867:Water; D000097245:Ursolic Acid; C071184:Gelucire 50-13