Physicochemical characterization and in vitro dissolution behavior of olanzapine-mannitol solid dispersions

The objective of the present work is to study the dissolution behavior of olanzapine from its solid dispersions with mannitol. Solid dispersions were prepared by melt dispersion method and characterized by phase solubility studies, drug content and in vitro dissolution studies. The best releasing dispersions were selected from release data, dissolution parameters and their release profiles. Solid state characterization techniques like Fourier transform infrared (FT-IR) spectroscopy, X-ray diffractometry, differential scanning calorimetry, near-infrared and Raman spectroscopy were used to characterize the drug in selected dispersions. The dispersions were also evaluated by wettability studies and permeation studies. The results of phase solubility studies and the thermodynamic parameters indicated the spontaneity and solubilization effect of the carrier. The release study results showed greater improvement of drug release from solid dispersions compared to pure drug, and the release was found to increase with an increase in carrier content. The possible mechanism for increased release rate from dispersions may be attributed to solubilization effect of the carrier, change in crystal quality, phase transition from crystalline to amorphous state, prevention of agglomeration or aggregation of drug particles, change in surface hydrophobicity of the drug, and increased wettability and dispersability of the drug in dissolution medium. The suggested reasons for increased release rate from dispersions were found to be well supported by results of solid state characterization, wettability and permeation studies. The absence of any interaction between the drug and the carrier was also proved by FT-IR analysis.

O objetivo do presente trabalho é estudar o comportamento de dissolução da olanzapina a partir de suas dispersões sólidas de manitol. As dispersões sólidas foram preparadas por dispersão por fusão e caracterizadas por estudos de solubilidade de fase, conteúdo de fármaco e dissolução in vitro. As melhores dispersões quanto à liberação foram selecionadas a partir dos dados de liberação, parâmetros de dissolução e perfis de liberação. Técnicas de caracterização de estado sólido como espectroscopia no infravermelho pela transformada de Fourier (FTIR), difratometria de raios X, calorimetria de varredura diferencial, infravermelho próximo e espectroscopia Raman foram utilizadas para caracterizar os fármacos a partir das dispersões selecionadas. As dispersões foram, também, avaliadas pelos estudos de capacidade de umedecimento e permeação. Os resultados dos estudos de solubilidade de fase e os parâmetros termodinâmicos indicaram a espontaneidade e o efeito de solubilização do transportador. Os resultados dos estudos de liberação mostraram maior aperfeiçoamento da liberação do fármaco das dispersões sólidas, comparativamente à do fármaco puro, e descobriu-se que a liberação aumenta com o aumento do conteúdo de transportador. O mecanismo possível para o aumento da taxa de liberação das dispersões pode ser atribuído ao efeito de solubilização do transportador, mudança da qualidade do cristal, transição de fase cristalina para estado amorfo, prevenção da aglomeração ou agregação das partículas do fármaco, mudança na superfície de hidrofobicidade do fármaco e aumento da capacidade de umedecimento e dispersividade do fármaco no meio de dissolução. As razões sugeridas para o aumento da taxa de liberação a partir das dispersões foram apoiadas pelos resultados da caracterização do estado sólido, capacidade de umedecimento e pelos estudos de permeação. A ausência de qualquer interação entre o fármaco e o transportador foi, também, comprovada pela análise no FTIR.

Gut permeability to lactulose and mannitol differs in treated Crohn's disease and celiac disease patients and healthy subjects

The gut barrier monitors and protects the gastrointestinal tract from challenges such as microorganisms, toxins and proteins that could act as antigens. There is evidence that gut barrier dysfunction may act as a primary disease mechanism in intestinal disorders. The aim of the present study was to evaluate the barrier function towards sugars after the appropriate treatment of celiac disease and Crohn's disease patients and compare the results with those obtained with healthy subjects. Fifteen healthy volunteers, 22 celiac disease patients after 1 year of a gluten-free diet, and 31 Crohn's disease patients in remission were submitted to an intestinal permeability test with 6.0 g lactulose and 3.0 g mannitol. Six-hour urinary lactulose excretion in Crohn's disease patients was significantly higher than in both celiac disease patients (0.42 vs 0.15 percent) and healthy controls (0.42 vs 0.07 percent). Urinary lactulose excretion was significantly higher in celiac disease patients than in healthy controls (0.15 vs 0.07 percent). Urinary mannitol excretion in Crohn's disease patients was the same as healthy controls (21 vs 21 percent) and these values were significantly higher than in celiac disease patients (10.9 percent). The lactulose/mannitol ratio was significantly higher in Crohn's disease patients in comparison to celiac disease patients (0.021 vs 0.013) and healthy controls (0.021 vs 0.003) and this ratio was also significantly higher in celiac disease patients compared to healthy controls (0.013 vs 0.003). In spite of treatment, differences in sugar permeability were observed in both disease groups. These differences in the behavior of the sugar probes probably reflect different mechanisms for the alterations of intestinal permeability.

Intestinal permeability and malabsorption of rifampin and isoniazid in active pulmonary tuberculosis

Low antimycobacterial drug concentrations have been observed in tuberculosis (TB) patients under treatment. The lactulose/mannitol urinary excretion test (L/M), normally used to measure intestinal permeability, may be useful to assess drug absorption. The objective of this research was to study intestinal absorptive function and bioavailability of rifampin and isoniazid in TB patients. A cross sectional study was done with 41 patients and 28 healthy controls, using the L/M test. The bioavailabilities of rifampin (R) and isoniazid (H) were evaluated in 18 patients receiving full doses. Urinary excretion of mannitol and lactulose, measured by HPLC, was significantly lower in TB patients. The serum concentrations of the drugs were below the expected range for R (8-24 mcg/mL) or H (3-6 mcg/mL) in 16/18 patients. Analyzing the drugs individually, 12/18 patients had low serum concentrations of R, 13/18 for H and 8/18 for both drugs. We suggest that there is a decrease in the functional absorptive area of the intestine in TB patients, which would explain the reduced serum concentrations of antituberculosis drugs. There is a need for new approaches to improve drug bioavailability in TB patients.

Manitol y procedimientos neuroanestésicos / Mannitol and neuroanesthesical procedures

El manitol es un diurético hiperosmolar que se ha utilizado durante los últimos treinta años en procedimientos neuroanestésicos. Se han propuesto múltiples mecanismos para explicar su efecto sobre el edema cerebral: deshidratación cerebral ocasionada por aumento de la osmolaridad plasmática, vasoconstricción en respuesta a disminución de la viscosidad sanguínea y disminución de la formación de líquido cefalorraquídeo. Recientemente se ha estudiado su capacidad para reducir el daño isquémico, al disminuir los niveles de radicales libres en las zonas injuriadas. En la actualidad su uso se halla controvertido. entre sus ventajas se encuentran la disminución rápida y relativamente prolongada de la presión intracraneal, la preservación de la función renal y la forma sencilla de administración. Las alteraciones hidroelectrolíticas, la marcada variación interindividual de sus efectos y el riesgo de producir rebotes en la presión intracraneal demuestran que la infusión de manitol no carece de efectos nocivos. Se revisan las principales características farmacocinéticas, farmacodinámicas, indicaciones y efectos adversos del manitol, así como su utilidad en los principales procedimientos neuroanestésicos.

Edulcorantes y productos dietéticos / Sweeteners and dietetic products

Los edulcorantes son productos útiles empleados muy comúnmente en la alimentación de los pacientes diabéticos y en regímenes hipocalóricos. Se presenta un análisis crítico de los diferentes edulcorantes calóricos y no calóricos actualmente disponibles en el mercado nacional analizando el aporte energético así como las ventajas y desventajas de cada uno de ellos. Se describen las características químicas y metabólicas del aspartame, endulzante no calórico y se comentan las investigaciones que se realizaron para lograr la autorización de su uso por la Federal Drug Administration (FDA). Se hace énfasis en que el profesional de la salud, debe tener conocimientos sobre los edulcorantes y productos dietéticos, a objeto de instruir a los pacientes para la correcta selección de ellos

Radicais livres e manitol sublingual / Free radicals and sublingual mannitol

Foi estudada a açäo do manitol por via sublingual em um grupo de pacientes, em cujo sangue foram determinados radicais livres, lipoperóxidos e ceruloplasmina. Observou-se que: 60 minutos após a administraçäo de 1.800 mg do manitol houve uma reduçäo estatisticamente significativa dos radicais livres, que se normalizou 120 minutos depois. A açäo lipoperoxidativa significativa dos radicais livres, que se normalizou 120 minutos depois. A açäo lipoperoxidativa foi mais lenta, sendo observado um decréscimo significante duas horas após a ingestäo. Näo houve alteraçäo na atividade da ceruloplasmina. Tais achados sugerem a possibilidade de emprego do manitol por via sublingual