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Pellet-filled capsule

Pelleting, Spheronization and Capsule Filling

Hard gelatin capsules containing pellets are now a recognized delivery system for controlling or modifying the release of drugs in the body and there are an increasing number of products on the market. They offer advantages over monolithic devices such as tablets in that the risk of dose dumping is significantly reduced. Uniformity of pellet shape is essential both for coating and for subsequent filling into capsules.

In filling capsules with pellets, the first step is to extrude small rods with aspect ratio ~2, and then to 'spheronize' these before filling the capsules with the spherical pellets. Here we show how both simulations and neural computing models can provide valuable information on this complex problem.

Controlling the particle shape means that we need to understand the spheronization process. We have used the data mining approaches (neurofuzzy logic, embodied in the FormRules program) to determine how factors like the spheronization time, spheronizer speed and water content affect the particle shape. See the full results here. This study uses data taken from the literature (1). (Customers with a password can download the data set here.) An experimental design was used to generate these points - although 'designed' experiments are not required by FormRules.

The same data were used to optimize the process parameters, using the modeling and optimization capabilities of INForm. See the results from the full study here.

Simulations can be used to show how the reproducibility of capsule filling is affected by particle shape, size and size distribution. We have investigated these using the MacroPac particle packing program - see the full results here. They show that, as long as the sphericity of the particles is less than 1.2, reproducibility can be achieved. This work has been published(2).

In summary, the rules generated by FormRules highlighted the most important variables in the spheronization process and their interdependenies. This allowed a good model to be developed using INForm and provided an optimized formulation and process. Simulations using MacroPac provided the data to set realistic limits for pellet size shape and size distribution.

(1) L Baert, H Vermeersch, J P Remon, J Smeyers-Verbeke and D L Massart, International Journal of Pharmaceutics, 96 (1993) 225-229.

(2) R C Rowe, P York, E A Colbourn and S J Roskilly, "The influence of pellet shape, size and distribution of capsule filling - a preliminary evaluation of three-dimensional computer simulation using a Monte Carlo technique" International Journal of Pharmaceutics 300 (2005) 32-37

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