Protective effect of sucupira oil nanoemulsion against oxidative stress in UVA-irradiated HaCaT cells.

OBJECTIVES: Bioactive molecules derived from natural products combine the ability to absorb UV light and act as antioxidants. We developed an oil-based sucupira (native species of the Brazilian cerrado) nanoemulsion (NE) using a high-energy emulsification method and assessed its effectiveness in vitro. METHODS: An easily scalable high-pressure homogenization method was used to prepare the formulation. NE droplets mean diameter, pH, stability, conductivity and morphology were analysed. Formulation bioactivity was assessed using HaCaT cells. KEY FINDINGS: The formulation presented suitable pH and size for topic administration and was stable for over 90 days upon storage at 4, 25 and 45°C. The NE showed protective effect against oxidative stress and reduced levels of UVA-induced pro-inflammatory cytokines IL-6 and IL-8. CONCLUSIONS: A novel, stable and easily prepared formulation was obtained for encapsulation of sucupira oil. The protective effect of the formulation by cytokine inhibition in the early stage of the inflammatory process was shown in vitro. Combined with the antioxidant effect by inhibition of reactive oxygen species, the use of sucupira oil NE for prevention and treatment of UVA-induced stress could contribute to decrease the effects of UV radiation on skin ageing.

Effect of stearic acid on enalapril stability and dissolution from multiparticulate solid dosage forms.

Enalapril maleate (EM) is a widely used anti-hypertensive drug which is unstable when mixed with excipients. Enalaprilate and diketopiperazine (DPK) are the main degradation products of enalapril. The in situ preparation of enalapril sodium salt (NaE) has been used to improve drug stability in dosage forms; however, gas release and product rejection ensue when the chemical reaction for obtaining the sodium salt is not completely finished before packaging. This study evaluated the effect of stearic acid (SA) on enalapril stability in microcrystalline cellulose (MCC) pellets containing EM or NaE. MCC pellets containing SA were prepared by the extrusion-spheronization technique and characterized. Enalapril stability and dissolution were then evaluated. DPK and enalaprilate formation were reduced by the addition of SA in pellets containing EM. The overall enalapril degradation in these formulations was lower when compared with pellets containing EM or even NaE prepared without SA. The immediate-release characteristic was maintained by the addition of 5% crospovidone to all the formulations tested. The incorporation of SA into NaE pellets resulted in unexpected enalapril degradation, caused by the interaction of these compounds, as suggested by a thermal analysis of the SA-NaE binary mixture. The findings presented here showed that formulations containing SA could substitute the formation of NaE, since they provide better enalapril stability in solid dosage forms. In addition, it is suggested that the stabilization effects would be observed for other N-carboxyalkyl dipeptide analogs with angiotensin converting enzyme inhibition activity, since these new entities share the same degradation pathway of enalapril.

Preparation and characterization of solid oral dosage forms containing soy isoflavones

Soy isoflavones have been extensively used for menopausal symptoms and prevention of hormone-related cancer, osteoporosis and cardiovascular diseases. Commercially available forms of isoflavones include supplements, capsules and tablets. However, the non-standardization of soy isoflavones extracts and different dissolution profiles of these solid dosage forms highlight the need of additional studies on the development of well characterized pharmaceutical dosage forms of isoflavones. In this work, immediate release oral tablets of soy isoflavones were obtained and evaluated. Genistein and daidzein, were the main constituents of the dried soy extract. Preparation of the tables was accomplished in a rotary tableting machine following either a dry mixture for direct compression or wet granulation with different excipients. Powder, granules and tablets were evaluated for several parameters, including flow properties, Carr and Hausner indexes, hardness, friability, disintegration time and drug release profile. Also, a fast and validated HPLC analytical method for both genistein and daidzein was developed. Formulations containing sodium croscarmellose and sodium dodecyl sulfate resulted in better flowability as indicated by the flow rate and angle of repose, faster disintegration time and immediate release dissolution profile.

A high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using solid phase extraction for the simultaneous determination of plasma concentrations of enalapril and enalaprilate in hypertensive patients treated with different pharmaceutical formulations.

UNLABELLED: Enalapril maleate, available on the market in a variety of different pharmaceutical formulations, is commonly used for the control of systemic arterial hypertension. Many therapeutical failures have been reported thus far in clinical practice with respect to switching between different pharmaceutical formulations of the same product during pharmacological therapy. In the present study, plasma concentrations of enalapril and enalaprilate were measured in hypertensive patients undergoing treatment with different pharmaceutical formulations. MATERIALS AND METHODS: Pharmaceutical formulations studied included the reference brand product, a generic formulation, and a third drug product marketed as "similar"; plasma samples were obtained from 30 hypertensive volunteer patients. Drug was extracted from the plasma by solid phase extraction and determined by liquid chromatography-tandem mass spectrometry. The method was validated for the main analytical parameters. RESULTS: The analytical method developed in this study, using liquid chromatography-tandem mass spectrometry, was confirmed as suitable for application in the determination of plasma concentrations in patients and subsequently revealed statistically significant differences in plasma concentrations between the 3 treatment groups. CONCLUSIONS: Such differences reinforce the hypothesis that the bioequivalence tests currently proposed by the regulatory authorities to promote interchangeability between pharmaceutical formulations may not in fact represent a definitive parameter for guaranteeing similar plasma concentrations.