RESUMEN
Many different formulation techniques are available for designing controlled-release dosage forms. Five different erosion-controlled or diffusion-controlled delivery systems were evaluated to select the 1 most suitable for Sinemet CR. The system ultimately selected, containing carbidopa-levodopa 50-200 mg, is a monolithic matrix tablet designed to have both of its active components released by surface dissolution and erosion. This system was found to be the most effective following extensive in vitro testing, pharmacokinetic studies, and clinical trials. Sinemet CR releases both carbidopa and levodopa by a 1st-order release rate. Controlled-release dosage forms of levodopa with slower in vitro release rates have lower plasma levels.
Asunto(s)
Antiparkinsonianos/administración & dosificación , Carbidopa/administración & dosificación , Levodopa/administración & dosificación , Antiparkinsonianos/farmacocinética , Carbidopa/farmacocinética , Química Farmacéutica , Preparaciones de Acción Retardada , Combinación de Medicamentos/administración & dosificación , Combinación de Medicamentos/farmacocinética , Humanos , Levodopa/farmacocinética , ComprimidosRESUMEN
The point of zero charge of 36 carbonate-containing aluminum hydroxide gels decreased with increased carbonate-to-aluminum molar ratio. Theoretical analysis supported this observation and showed that the point of zero charge was sensitive to low fractional coverage of surface sites by carbonate and that divalent carbonate is the predominant form of carbonate on the surface. The implications of the pH-point of zero charge relationship of aluminum hydroxide on the viscosity, adsorptive properties, rate of filtration, and removal of sodium are discussed.
Asunto(s)
Hidróxido de Aluminio/análisis , Carbonatos/análisis , Adsorción , Fenómenos Químicos , Química Física , ViscosidadRESUMEN
Approximately 90% of the sodium present in a washed aluminum hydroxycarbonate gel was removed by exchange with magnesium. This behavior supports recent structural studies which have suggested that cations such as sodium serve as counterions in aluminum hydroxycarbonate gel. However, sodium could not be removed from dihydroxyaluminum sodium carbonate by exchange with magnesium because sodium is part of the crystal structure. It is hypothesized that aluminum hydroxycarbonate gels which resist removal of sodium are actually mixtures containing dihydroxyaluminum sodium carbonate in addition to aluminum hydroxycarbonate.
Asunto(s)
Hidróxido de Aluminio/análisis , Magnesio/análisis , Sodio/análisis , Antiácidos/análisis , Fenómenos Químicos , Química , Intercambio Iónico , Espectrofotometría Atómica , Espectrofotometría Infrarroja , Difracción de Rayos XRESUMEN
Carbonate-containing aluminum hydroxide was precipitated at constant pH at intervals of 0.5 pH units from pH 6 to 10 by pumping 0.5 M AlCl3 into the reaction vessel at a constant rate of 2 mL/min and infusing 2 M Na2CO3 at a rate necessary to maintain the desired pH. The pH of precipitation affected both the particle size and the composition of the precipitate. The particle size of the precipitate decreased as the pH of precipitation was increased from 6 to 10. The precipitates formed between pH 7.5 and 9.5 contained crystalline sodium aluminum hydroxycarbonate (dawsonite) in addition to amorphous carbonate-containing aluminum hydroxide.
Asunto(s)
Hidróxido de Aluminio/análisis , Carbonatos/análisis , Fenómenos Químicos , Precipitación Química , Química , Concentración de Iones de Hidrógeno , Tamaño de la Partícula , Espectrofotometría Infrarroja/métodos , Difracción de Rayos XRESUMEN
Carbonate was completely desorbed from amorphous aluminum hydroxycarbonate gel by purging with nitrogen. The reversibility of carbonate adsorption suggests that aluminum hydroxycarbonate particles are composed of planes of aluminum hydroxide with carbonate adsorbed at edge aluminum sites. A slow-reacting phase which was identified as a precursor of gibbsite, formed when the carbonate/aluminum molar ratio was less than 0.20.