Gastrointestinal mucositis induced during cancer treatment is considered a serious dose-limiting side effect of chemotherapy and/or radiotherapy. Frequently, interruption of the cancer treatment due to this pathology leads to a reduction in cure rates, increase of treatment costs and decrease life quality of the patient. Natural products such as Bidens pilosa L. (Asteraceae), represent a potential alternative for the treatment of mucositis given its anti-inflammatory properties. In this study, B. pilosa glycolic extract was formulated (BPF) with poloxamer, a mucoadhesive copolymer, was used for treatment of 5-fluorouracil (5-FU)-induced mucositis in mice. As expected, animals only treated with 5-FU (200 mg/kg) presented marked weight loss, reduction of intestinal villi, crypts and muscular layer, which was associated with severe disruption of crypts, edema, inflammatory infiltrate and vacuolization in the intestinal tissue, as compared to the control group and healthy animals only treated with BPF. On the other hand, the treatment of intestinal mucositis-bearing mice with BPF (75, 100 or 125 mg/kg) managed to mitigate clinical and pathologic changes, noticeably at 100 mg/kg. This dose led to the restoration of intestinal proliferative activity through increasing Ki-67 levels; modulated the expression of Bax, Bcl2 and p53 apoptotic markers protecting intestinal cells from cell death. Moreover, this treatment regulated lipid peroxidation and inflammatory infiltration. No acute toxic effects were observed with this formulation. This work demonstrated that BPF was safe and effective against 5-FU-induced intestinal mucositis in mice. Additional studies are already in progress to further characterize the mechanisms involved in the protective effects of this technological formulation toward the development of a new medicine for the prevention and treatment of intestinal injury in patients undergoing chemotherapy/radiotherapy.

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.

Carvedilol (CARV) is a widely used non-selective b-blocker, which has shown low bioavailability after oral administration (20 %) due to its low water solubility and intense first-pass metabolism. Lipid-based drug delivery systems have been proposed to improve CARV oral bioavailability. An evaluation of drug-excipient compatibility is needed to clarify potential physical and chemical interactions between them and therefore guarantee a correct selection of excipients. However, to date there are no reports on the systematic evaluation of CARV-lipid excipient compatibility. Thus, the aim of this study was to evaluate the compatibility of CARV with the lipid excipients commonly used for the development of lipid-based formulations. Thermal analysis techniques (DTA and TG/DTG), Fourier transform infrared spectroscopy and isothermal stress testing (IST) were used for this purpose. The results of this study showed that 4 of the 10 lipid excipients studied were incompatible with CARV. The strongest thermal and spectroscopic modifications were observed in CARV mixtures with oleic acid, lauric acid, lauroyl polyoxylglycerides (Gelucire Ò 44/14) and glyceryl caprylate/caprate (Capmul Ò MCM). In addition, these mixtures resulted in significant decreases in drug content after aging. On the other hand, palmitic acid, stearic acid, glyceryl behenate (Compritol ATO Ò 188), tribeheninPEG (Emulium Ò 22), polyglyceryl-6-isostearate (Plurol Isostearique Ò ) and diethylene glycol monoethyl ether (Transcutol HP Ò ) were considered good candidates for developing self-emulsifying drug delivery systems and for preparing lipid microparticle or nanoparticle containing CARV. These findings denote the relevance of combining thermal and spectroscopic techniques with thermal stress testing for the accurate determination of druglipid excipient compatibility.

Enalapril maleate is a widely used drug, which is chemically unstable when mixed with excipients resulting in enalaprilat and diketopiperazine as the main degradation products. The preparation of enalapril sodium salt has been used to improve drug stability in solid dosage forms; however, product rejection is observed when the chemical reaction for obtaining the sodium salt is not completely finished before packaging. In this study, granules were prepared by melting granulation using stearic acid or glyceryl monostearate, with a view to developing more stable enalapril maleate solid dosage forms. The granules were prepared in a laboratory-scale high shear mixer and compressed in a rotary machine. Size distribution, flow properties, in vitro drug release and enalapril maleate chemical stability were evaluated and compared with data obtained from tablets prepared without hydrophobic binders. All formulations showed good physical properties and immediate drug release. The greatest improvement in the enalapril maleate stability was observed in formulations containing stearic acid. This study showed that hot melting granulation could be successfully used to prepare enalapril maleate granules which could substitute the in situ formation of enalapril sodium salt, since they provided better enalapril stability in solid dosage forms.

Como a (des)valorização dos praças do corpo de bombeiros militar do estado de Goiás pode interferir na qualidade de saúde destes profissionais: uma primeira aproximação de pesquisa How the (un)valuation of the military firefighters of the state of Goiás can interfere with the quality of health of these professionals: a first research approach