Tomer, Gil; (1999) An investigation of the role of water in the process of extrusion/spheronization of model formulations. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Extrusion/Sphemization is a method for the manufacture of pellets (small spherical particles) used in the pharmaceutical area. This work investigates the role of the most common liquid used in extrusion/spheronisation formulations, water, in terms of the success and the failure of the process. Five model drugs from the same chemical family were chosen. The model drugs were esters of gallic acid (methyl, propyl and butyl paraben), p-hydroxy benzoic acid and propyl gallate. All five drug models mixed with different ratios of microcrystalline cellulose (MCC) and water were extruded and spheronized. The different process parameters were collected and analyzed, such as steady-state extrusion force, the shape and size of pellets produced from extrudates etc. The results showed that four out of the five drug models can be considered drugs that go through the extrusion/spheronization process well. Formulations from each material were extruded and the extrudates were collected in different fractions, and the amount of water in each fraction was determined. It was found that the amount of water in the initial formulation and the extrusion speed had a great effect on the amount of water in the extrudates, and that the extrusion/spheronization process is tolerant of a degree of water movement. A centrifuge method was employed to evaluate a water retention parameter for the different materials and their mixtures with MCC. It was found that although all materials are similar in their chemical structure, an obviously different water retention capacity was recorded which was related to their hydrogen bonding solubility parameter. Magnetic resonance imaging (MRI) was used to map the water distribution in plugs and in the extrudates. From examining the plugs it was found that two types of water movements occurred in the barrel, different in their direction. Which type of water movement is dominant is dependent on the speed of extrusion. The examination of the extrudates did not produce clear information, probably because of the limitations of scale. Powder compacts made from the different model drugs were tested under creep conditions, but the results were not reproducible. By extruding the model drugs inside a transparent barrel and tracking the progress of marker stripes it was possible to show that the different layers inside the barrel moved in a fluctuating manner.

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