RESUMO
This study evaluated the possible use of a fraction of brewers' spent grain rich in arabinoxylans (BSG-AX) as an excipient that modifies the release of class III drugs (Biopharmaceutics Classification System), by determining the release profile of metformin hydrochloride (MH), in a water medium. The cumulative percentage of MH release showed the best linear fit when modeled with the cumulative distribution function (CDF) of the Weibull distribution (R2 = 0.993 ± 0.001). According to the Korsmeyer-Peppas model, the first stage of MH release is regulated by a super case-II transport mechanism controlled by the expansion and relaxation of BSG-AX. Finally, with the Hixson-Crowell model, a release rate (kHC) of 0.350 ± 0.026 h-13 was obtained (R2 = 0.996 ± 0.007). BSG-AX constitutes a suitable material for producing prolonged drug release vehicles; however, additional research is required to provide a better encapsulation of the active ingredients to ensure their optimal applicability and performance.
Assuntos
Água , Xilanos , Liberação Controlada de Fármacos , Grão ComestívelRESUMO
Metformin has been associated with cardioprotection, vasorelaxation and normalization of endothelial function during type 2 Diabetes Mellitus. However, few studies have analysed its effects on vascular adrenergic system. Our study has evaluated the vasopressor responses induced by sympathetic stimulation or by i.v. bolus injections of the agonists noradrenaline (α1/2), methoxamine (α1) and UK 14,304 (α2) in rats with fructose-induced insulin resistance chronically pretreated with either metformin or EGL-6M (N-benzylbiguanide), a novel analogue of metformin. Rats were treated with fructose (15%) or tap water (control) during 16 weeks. Next, both groups were treated daily during 4 weeks with: (1) vehicle; (2) metformin (50mg/kg); or (3) EGL-6M (50mg/kg). Blood glucose and plasma insulin were determined before and after administration of glucose during oral glucose tolerance test. Animals treated with fructose showed hyperinsulinemia and insulin resistance, which were decreased by metformin and EGL-6M. In animals treated with fructose, the vasopressor responses induced by: (1) sympathetic stimulation were decreased; (2) noradrenaline were increased; and (3) methoxamine and UK 14,304 remained unaffected compared with control group. In control animals, metformin failed to modify the vasopressor responses analysed, while EGL-6M increased the vasopressor responses to sympathetic stimulation. In rats treated with fructose, metformin decreased vasopressor response to noradrenaline but did not modify the sympathetic stimulation responses. EGL-6M increased the vasopressor responses to sympathetic stimulation without modifying those to noradrenaline, methoxamine or UK 14,304. Collectively, these data suggest that EGL-6M is capable to increase insulin sensitivity and the vasopressor sympathetic outflow in rats.
Assuntos
Biguanidas/farmacologia , Frutose/efeitos adversos , Resistência à Insulina , Metformina/farmacologia , Receptores Adrenérgicos/metabolismo , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Agonistas Adrenérgicos/farmacologia , Animais , Biguanidas/química , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Insulina/sangue , Masculino , Metformina/química , Ratos , Ratos WistarRESUMO
The aim of the present study was to analyze the effect of a combination of metformin hydrochloride and melatonin on oxidative stress together with a biochemical and histopathological analysis of the livers of Wistar rats induced with PCOS. The results indicated that a combination of the drugs was more effective in the reduction of plasmatic levels of liver enzyme alanine aminotransferase, nitric oxide and total glutathione, and decreased the inflammatory response and histopathological damage, producing results that were significantly similar to animals from the control group. A mixture of the drugs produced more effective results against liver toxicity caused by PCOS, encouraging the normalization of biochemical parameters. During pregnancy, there was reduced oxidative stress compared to monotherapeutic use of these drugs. Interestingly, the combination of the drugs caused a physiological reaction similar to responses identified in healthy rats without induction of the PCOS control group. However, the clinical and physiological effectiveness of the combination should be further explored, especially with respect to the possible side effects on offspring.
Assuntos
Antioxidantes/administração & dosagem , Fígado/efeitos dos fármacos , Melatonina/administração & dosagem , Metformina/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Animais , Quimioterapia Combinada , Feminino , Fígado/metabolismo , Fígado/patologia , Estresse Oxidativo/fisiologia , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Gravidez , Ratos , Ratos Wistar , Resultado do TratamentoRESUMO
Metformin hydrochloride (MH) is an oral hypoglycemic agent and a high-dose drug that has poor flow and compression properties. In this study, the feasibility of developing adequate, low cost 500mg tablets of metformin hydrochloride by wet granulation was tested with several binders (Starch / PVP K30®; Starch1500® /PVP K30®, PVP K30® and PVP K90®) in a simple tablet press of the type used in small pharmaceutical laboratories. The drug powder was tested for ability to flow, by determining Carr?s Index (CI) and the Hausner ratio (HR). Differential scanning calorimetry and thermogravimetric analysis were carried out on isolated MH and 1:1 (w/w) binary mixtures with the excipients. The size distribution, friability, flow properties and drug content of the granules were analyzed, as were the hardness, friability, disintegration, dissolution and uniformity of the dosage form. The drug powder showed CI > 22% and HR > 1.25, characteristic of a poor flow powder, and no significant incompatibilities with the excipients. All the granules showed adequate flow properties and were suitable for pressing into tablets, all of which complied with pharmacopeial specifications. The starch /PVP K30® and starch 1500®/PVP K30® mixtures were best for producing 500 mg MH tablets.
Cloridrato de metformina é um fármaco hipoglicemiante oral que apresenta propriedades pobres de fluxo e compressibilidade. Este trabalho teve como objetivo o desenvolvimento de comprimidos de baixo custo,após granulação por via úmida, contendo 500 mg de cloridrato de metformina e diferentes aglutinantes (F1-amido / PVP K30®; F2- Starch 1500® / PVP K30®, F3-PVP K30®, F4- PVP K90®) em máquinas de compressão de baixo desempenho usadas em laboratórios farmacêuticos de pequeno porte. As propriedades defluxo do fármaco foram analisadas através do índice de Carr (IC) e fator de Hausner (FH). Cloridrato de metformina e suas misturas binárias com os excipientes na relação 1:1 (m/m) foram analisadas por calorimetria diferencial por varredura e análise termogravimétrica. Os granulados foram analisados quanto a distribuição granulométrica, friabilidade, propriedades de fluxo e teor e os comprimidos em relação à dureza, friabilidade, desintegração, dissolução e uniformidade de conteúdo.O cloridrato de metformina apresentou IC > 22% e FH> 1,25, característicos de fluxo pobre e não apresentou incompatibilidades com os outros excipientes. Todos os granulados demonstraram adequadas propriedades de fluxo e facilidade no processo de compressão. Os comprimidos apresentaram conformidade com as especificações farmacopeicas. As misturas amido / PVPK30® e Starch 1500® / PVP K30® foram mais adequadas para produzir comprimidos de cloridrato de metformina 500 mg.