MacRitchie, Kenneth Andrew; (1993) Rheological evaluation of mixtures of lactose, microcrystalline cellulose and water suitable for the preparation of spherical granules. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Extrusion/spheronisation is a method used widely in the pharmaceutical industry to produce small spheres (approximately 1mm in size) of formulated drug. These spheres are the ideal shape for coating and the technique is often used to produce spheres with a sustained-release action. The technique does not always produce spheroids because of its high sensitivity to both the drug formulation and to process parameters. Previous studies undertaken have identified the relative importance of process parameters and drug formulation on the extrusion/spheronisation technique and have established that the rheological nature of the formulation is of primary importance. In this work the rheology of formulations suitable for extrusion and spheronisation has been assessed using the established technique of capillary rheometry and compared to that of controlled-stress rheometry. Capillary rheometry requires several days work to analyse a formulation and consequently the technique is unsuitable for quality control purposes and time-consuming for formulation development. Controlled-stress rheometry has the advantage of being far quicker to perform than capillary rheometry. In addition it provides information on the relative elasticity and viscosity of the material that cannot be obtained from capillary rheometry. Formulations investigated contained lactose as a model water-soluble drug and microcrystalline cellulose as the excipient that allows the formation of good quality extrudate. Spheres were successfully produced with a lactose content of greater than 70% dry weight. Results indicate that controlled-stress rheometry is an accurate and sensitive alternative to capillary rheometry in establishing the rheological parameters of a drug formulation. With variation in the moisture content of the formulation the elastic component of the material is affected more than the viscous component and these changes can be used to explain why a formulation will not spheronise. Consequently the technique can be used to predict the behaviour of materials before they undergo extrusion/spheronisation and therefore is a useful tool in the development of spherical granules.

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