This work reports the preparation of tablets by direct compression of sodium alendronate-loaded microparticles, using pullulan as filler. The tableting properties of pullulan were compared with those of microcrystalline cellulose and lactose. Pullulan tablets showed low variations in average weight, thickness and drug content. Moreover, these tablets exhibited a higher hardness compared to the other excipients.In vitro release studies showed that only pullulan was capable to maintain gastroresistance and release properties of microparticles, due to its ability to protect particles against damage caused by compression force. Thus, pullulan was considered an advantageous excipient to prepare tableted microparticles.Uniterms: Pullulan. Excipients. Microparticulate tablets. Sodium alendronate.Neste trabalho relata-se a preparação de comprimidos pela compressão direta de micropartículas contendo alendronato de sódio, utilizando o pullulan como diluente. As propriedades dos comprimidos de pullulan foram comparadas com as de comprimidos de celulose microcristalina e de lactose. Os comprimidos de pullulan mostraram baixa variação no peso médio, espessura e teor. Por outro lado, estes apresentaram altos valores de dureza comparados aos preparados com os outros excipientes. Através dos estudos de liberação in vitro pode-se observar que apenas o pullulan foi capaz de manter a gastrorresistência e as propriedades de liberação das micropartículas, o que se deve à sua capacidade de proteger as partículas do dano causado pela força de compressão. Dessa forma, o pullulan foi considerado um excipiente vantajoso para a preparação de comprimidos microparticulados.Unitermos: Pullulan. Excipientes. Comprimidos microparticulados. Alendronato de sódio.

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Risedronate, an anti-osteoporotic drug, is associated with low patient compliance due to the upper gastrointestinal side-effects and stringent dosing regimes. This study aimed to prepare and characterize risedronate-loaded Eudragit® S100 microparticles and develop a final dosage form by the compression of microparticles using direct tableting excipients. Microparticles were prepared by spray-drying and presented yield of 54%, encapsulation efficiency higher than 90%, mean diameter of 3.3 µm, moisture content around 8% and exhibited spherical shape and poor flowability. At pH 1.2, 23% of risedronate was released from microparticles in 120 min, while at pH 6.8 the drug took 90 min to reach 99.5%. Microparticles were compressed into tablets using microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide and 2 polyvinylpyrrolidone concentrations (5% and 15%). Tablets presented low variations in weight, thickness and drug content. Besides, the formulations showed sufficient hardness, low friability and disintegrated in less than 15 min. In acid medium, no more than 16% of the drug was released in 120 min, while in intestinal medium the formulations prolonged the risedronate release for 240 min. Finally, the developed tableted microparticles can be considered a promising dosage form for oral risedronate administration.

Sodium alendronate is an antiresorptive drug used for the treatment of postmenopausal osteoporosis. However, its oral administration is associated with low bioavailability and gastroesophageal irritation. This work aimed at developing tablets containing sodium alendronate-loaded microparticles by direct compression to achieve a safe and effective form. The parameters evaluated were average weight, hardness, thickness and drug content. In vitro release tests were carried out using simulated gastric and intestinal fluids, and the profiles were analyzed through the Korsmeyer-Peppas mono-or biexponential dependent approaches. Tablets presented adequate average weight, thickness, good mechanical properties and drug content close to 100%. Moreover, the formulation released less than 11% of sodium alendronate in gastric fluid, exhibiting a good gastroresistance. At pH 6.8, almost 100% of the drug was released in 12h, showing a prolonged profile. The mathematical modeling indicated that the experimental data was better fitted to the biexponential equation. Furthermore, a good correlation coefficient was obtained for the Korsmeyer-Peppas model and the release exponent suggested that the drug dissolution was driven by anomalous transport. In conclusion, the microparticulated tablets can be considered a promising alternative for oral delivery of sodium alendronate.Uniterms: Microparticulated tablets/release profile. Sodium alendronate/oral administration. Sodium alendronate/controlled release/in vitro study.O alendronato de sódio é um fármaco da classe dos bisfosfonatos, comumente utilizado no tratamento da osteoporose pós-menopausa. Entretanto, sua administração oral está associada à baixa biodisponibilidade e irritação gastroesofágica. Este trabalho objetivou o desenvolvimento de comprimidos contendo micropartículas de alendronato de sódio por compressão direta, a fim de obter uma forma segura e eficaz. Os parâmetros avaliados foram peso médio, dureza, espessura e teor de fármaco. Estudos de liberação in vitro foram realizados utilizando fluído gástrico e intestinal simulado e o perfil de liberação foi analisado pelos modelos matemáticos de Korsmeyer-Peppas, mono-e biexponencial. Os comprimidos apresentaram peso médio adequado, espessura, dureza e teor próximo a 100%. Além disso, a formulação liberou menos de 11% do fármaco em fluído gástrico, mostrando uma boa gastrorresistência. Em pH 6,8, em torno de 100% do fármaco foram liberados em 12 h, apresentando liberação prolongada. A modelagem matemática indica que os resultados seguem a equação biexponencial. Pela análise do expoente de liberação obtido no modelo de Korsmeyer-Peppas sugere-se que a dissolução do fármaco ocorre por transporte anômalo. Concluindo, a preparação dos comprimidos microparticulados pode ser considerada uma alternativa promissora para a liberação oral do alendronato de sódio. Unitermos:Comprimidos microparticulados/perfil de liberação. Alendronato de sódio/administração oral. Alendronato de sódio/liberação controlada/estudos in vitro.