A granule is a composite mixture of one or more type of primary solid particles (API, excipient, etc.) held toghether by a binder, and represents a commonly used precursor or final dosage form for the delivery of solid active pharmaceutical ingredients. Granules are either transiotry, existing only from one process step to another (e.g., as a feed for tableting) or they are the final product on its own (e.g., when filled into capsules). In both considerations the spatial arrangement of formulation ingredients within the granule matrix is very important in regard to its mechanical properties (visco-elastic response during tabletting) and API release pattern during dissolution.

In our recent work [1, 2] we have established a novel methodology that can be used to control the spatial distribution of the API (or any other component of interest) within the granule structure by introducing the API as a solid dispersion with in-situ melt or aqueous polymeric binders. In the present work we examine the dissolution behaviour of tablets compressed from pre-designed granules of two types, i) granules with model API randomly distributed in the structure matrix and ii) granules with the model API encapsulated in its core.

We will also demonstrate the above mentioned approach to produce granules that contain compartmentalised reactive particles. These granules release an active ingredient produced in-situ as a result of the interaction between the reactive precursor particles contained within the granule. Since granule properties profoundly influence the tablet dissoultion charactersitics, the idea of comparmentalised granules would offer a range of applications in the area where in-situ API are essential formulation or physiological requirements.

References:
[1] Ansari M.A., and Stepanek F. 2006, “Design of granule Structure: computational methods and experimental realization” AIChE Journal , vol 52, no 11, pp: 3762-3774.
[2] Ansari, M.A., and Stepanek F. 2008, “The evolution of microstructure in threecomponent granulation and its effect on dissolution”, Particulate Science and Technology , vol 26, no 1, pp: 55-66.