RESUMO
Nifedipine is a potent anti-hypertensive, which is poorly orally bioavailable on account of first-pass metabolism, short half-life, and low water solubility. This study aimed to develop a microemulsified system with low surfactant concentration and to evaluate the influence of microemulsion (ME) phase behavior on skin permeation of nifedipine, as drug model. Thereafter, MEs were obtained using PPG-5-CETETH-20, oleic acid, and phosphate buffer at pH 5.0. The selected MEs were isotropic, with droplet diameters less than 10 nm, polydispersity index < 0.25, and pH between 5.0 and 5.2. MEs presented low viscosity and Newtonian behavior. SAXS results confirmed bicontinuous and oil-in-water (o/w) MEs formation. The presence of the drug promoted only very slight modifications in the ME structure. The MEs presented ability to deliver nifedipine via the transdermal route when in comparison with the control. Nevertheless, the skin permeated and retained amounts from the o/w and bicontinuous formulations did not differ significantly. The ATR-FTIR demonstrated that both formulations promoted fluidization and disorganization of lipids and increased the drug diffusion and partition coefficients in the skin. In conclusion, PPG-5-CETETH-20 MEs obtained proved to be effective skin permeation enhancers, acting by rising the coefficients of partition and diffusion of the nifedipine in the skin.
Assuntos
Nifedipino , Pele , Administração Cutânea , Emulsões/química , Nifedipino/metabolismo , Espalhamento a Baixo Ângulo , Pele/metabolismo , Tensoativos/química , Água/química , Difração de Raios XRESUMO
Orotic acid (OA), a heterocyclic compound also known as vitamin B13, has shown potent antimalarial and cardiac protection activities; however, its limited water solubility has posed a barrier to its use in therapeutic approaches. Aiming to overcome this drawback, OA freeze-dried nanocrystal formulations (FA, FB, and FC) were developed by using the high-energy milling method. Polysorbate 80 (FA) and povacoat® (FC) were used alone and combined (FB) as stabilizers. Nanocrystals were fully characterized by dynamic light scattering, laser diffraction, transmission electron microscopy, thermal analysis (thermogravimetry and derivative thermogravimetry, and differential scanning calorimetry), and X-ray powder diffraction revealing an acceptable polydispersity index, changes in the crystalline state with hydrate formation and z-average of 100-200 nm, a remarkable 200-time reduction compared to the OA raw material (44.3 µm). Furthermore, saturation solubility study showed an improvement of 13 times higher than the micronized powder. In addition, cytotoxicity assay revealed mild toxicity for the FB and FC formulations prepared with povacoat®. OA nanocrystal platform can deliver innovative products allowing untapped the versatile potential of this drug substance candidate.