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The effect of sodium bicarbonate (SB) on the swelling behavior and the sustained release of floating systems was studied with varied proportions of this excipient and metronidazole. Two polymers with different hydration characteristics, Methocel K4M and Carbopol 971P NF, were used to formulate the matrices. Under in vitro dissolution conditions, the addition of SB to metronidazole sustained-release tablets modifies the matrix hydration volume, increasing at the beginning, reaching a maximum, and then declining. Pure Carbopol matrices show a rapid hydration with a limited further effect of the SB and metronidazole loads. Methocel show a significant increase of the apparent hydration volume due to SB addition with no further notable change due to metronidazole load. Increasing the metronidazole load reduces the floating time of Carbopol matrices while no effect on Methocel matrices could be observed within 8 hours dissolution. Matrices show increasing release constant values (k) as the metronidazole load increases. Methocel matrices release the drug 10% to 15% faster than Carbopol matrices. SB increases the cumulative amount of drug released from Methocel but not that releasing from Carbopol. These results are attributed to the intrinsic polymer properties, the barrier effect of CO(2) bubbles, and the matrix volume expansion produced after addition of SB.

The sustained release of amoxicillin is desired to be confined to the upper gastrointestinal tract to treat certain kind of infections. In vitro dissolution, at pH 1.2, of amoxicillin sustained release tablets has been studied varying the proportion of Carbopol 971P NF and sodium alginate as well as the ethanol/water proportion in the granulation fluid. M(t), the amount of drug released at time (t) and defined in terms of the total drug released over a long time period (M(inf), was described by M(t)/M(inf) = kt(n). Matrices with increasing proportions of sodium alginate showed increasing values of the exponent indicative of the release mechanism (n) and increasing release constant values (k). This is attributed to a drop in the coherence of the polymeric matrix with increasing alginate proportions that produces an increasing polymer relaxation and erosion. Decreasing Carbopol 971P NF proportions reduce the amount of dissolved polymer during granulation, producing a lesser obstruction of amoxicillin dissolution. Alginate proportions of 80% produce near zero order release profiles. Granules obtained with increasing ethanol proportions showed increasing release constant values and a minor change in the exponent (n) values. This is considered a result of lower polymer dissolution during granulation that allows a lesser matrix coherence and a greater amoxicillin dissolution. Alginate matrices granulated with different ethanol/water proportions showed no significant changes in the amoxicillin release profile. There is a trend toward increasing floating times with increasing Carbopol 971P NF proportions.

The properties of metronidazole/Methocel K4M sustained release floating tablets have been studied varying the proportion of the lubricant, stearic acid, on formulations with and without sodium bicarbonate. The variables studied include technological properties of the tablets such as tablet hardness and ejection pressure, the drug release profile, the hydration kinetics and the floating behaviour. The presence of stearic acid and sodium bicarbonate improves the floating behaviour for more than 8 hours. The hydration volume, the tablet hardness and the ejection pressure decrease as the stearic acid content increases and the polymer content decreases. Drug dissolution increases with increasing proportions of stearic acid and decreasing proportions of the polymer in the tablets. The presence of sodium bicarbonate extends the differences in dissolution produced by stearic acid. These results are attributed to decreasing matrices coherence with an increasing quantity of stearic acid and a reducing polymer proportion. The carbon dioxide bubbles produced by sodium bicarbonate expand the matrices facilitating the dissolution, although their presence obstructs also the diffusion path through the hydrated gel layer. Uniterms:Metronidazole. Methocel K4M. Stearic acid. Matrices hydration. Gastric retention. Sodium bicarbonate. Sustained release. Drugs/release mechanism.Estudaram-se as propriedades de comprimidos flutuantes de metronidazol/Methocel K4M de liberação controlada, variando-se a proporção do lubrificante, ácido esteárico, nas formulações com e sem bicarbonato de sódio. As variáveis estudadas incluem propriedades tecnológicas dos comprimidos, tais como dureza, pressão de ejeção, perfil de liberação do fármaco, cinética de hidratação e comportamento de flutuação. A presença de ácido esteárico e do bicarbonato de sódio melhora o comportamento de flutuação para mais de 8 horas. O volume de hidratação, a dureza e a pressão de ejeção do comprimido decrescem à medida que o conteúdo de ácido esteárico e de polímero diminui. A dissolução do fármaco aumenta com o aumento das proporções de ácido esteárico e a diminuição das proporções de polímero nos comprimidos. A presença de bicarbonato de sódio amplia as diferenças na dissolução produzidas pelo ácido esteárico. Estes resultados são atribuídos à coesão decrescente das matrizes, com o aumento da quantidade de ácido esteárico e a redução da proporção de polímero. Bolhas de dióxido de carbono produzidas pelo bicarbonato de sódio expandem as matrizes, facilitando a dissolução, embora a presença delas obstrua, também, a difusão através da camada de gel hidratado. Unitermos:Metronidazol. Methocel K4M. Ácido esteárico. Hidratação das matrizes. Retenção gástrica. Bicarbonato de sódio. Fármacos/mecanismo de liberação.

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