Synergistic effect of polyethylene glycol and superdisintegrant on dissolution rate enhancement of simvastatin in pellet formulation.

Synergistic effect of polyethylene glycol and superdisintegrant on dissolution rate enhancement of simvastatin in pellet formulation.

Afrasiabi Garekani, Hadi;Aftabi, Seyede Fatemeh;Nia, Fatemeh Fahimi;Javidi, Mohammad;Nokhodchi, Ali;Sadeghi, Fatemeh;
pharmaceutical development and technology 2019 Vol. 24 pp. 720-728
271
afrasiabi-garekani2019synergisticpharmaceutical

Abstract

Slow dissolution is a major drawback for poorly water-soluble drugs when they are extruded-spheronized with microcrystalline cellulose (MCC). Therefore, the aim of the current study was to explore excipients to enhance the dissolution of simvastatin without compromising the extrudability and sphericity of pellets. Pellets containing simvastatin, MCC and polyethylene glycols (PEGs) or superdisintegrants were prepared by extrusion-spheronization and their micromeritics and mechanical properties, drug release and solid state of simvastatin were studied. All formulations produced pellets with reasonable size and sphericity. Generally, the inclusion of PEG and superdisintegrants decreased crushing strength and elastic modulus of pellets and increased the dissolution rate of simvastatin. A substantial increase in dissolution rate was observed when a combination of PEG and superdisintegrant was used due to the formation of more porous matrix, faster disintegration and remarkable reduction in drug crystallinity. It was interesting to note that the use of PEG and superdisintegrant had a synergistic effect on the dissolution enhancement of simvastatin in pellet formulation. The results of this study confirmed that a simple method of extrusion-spheronization can be employed to enhance the dissolution of simvastatin in multi particulates dosage form which can also be employed for other poorly water-soluble drugs.

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44778
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10.1080/10837450.2019.1584632
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