Effect of different production variables on the physical properties of pellets prepared by extrusion-spheronization using a multivariate analysis

John Rojas

Abstract


The spheronization process has been widely used in recent years in multiparticulate oral formulations because it is a simple and rapid technology. It offers advantages over other dosage forms such as tablets due to the more uniform and predictable transport in the gastrointestinal tract. The spherical symmetry renders good flow properties, high mechanical strength and low friability. The aim of the present study was to evaluate the effects of spheronization rates, spheronization time and amount of water content on shape descriptors and physical properties of pellets produced from microcrystalline cellulose (MCC). Approximately, 50 g of MCC were hydrated, passed through a mesh # 8 sieve and spheronizated at rates of 4, 6, 8, 10 and 12 Hz and residence times of 30, 60, 90, 120 and 180 s in 25 experimental runs.  In a separate experimental set moisture levels of 23.1, 37.5, 47.4, 54.5 and 60% were employed at the optimal operational conditions of 12 Hz and 180s. A multivariate analysis was used to study the effect of these factors on the response variables (shape descriptors, densification, breaking strength, friability, porosity, etc). A microscopy analysis was used to evaluate the shape descriptors using the ImageJ® software. Pellets properties such as compressibility, friability, true density, hardness, flow rate and mass were also evaluated. Pellets of a large size were obtained with high spheronization rate, spheronization time and high moisture content. Shape descriptors related to the size such as area, perimeter, and mean diameter increased with increasing spheronization time and spheronization rate. Further, pellets obtained from high spheronization rate were more spherical than those obtained at low speeds. Conversely, shape descriptors related to the morphology such as circularity, and roundness and pellet strength remained virtually unchanged as operational conditions changed. Further, spironolactone release rates were inversely related to drug loading. The moisture level was the most critical factor to increase particle size and improved the spherical morphology. On the other hand, spheronization rate was the determining factor for pellet properties such as densification, compressibility and compactibility.

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References


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