Extrudierte Fettmatrizes mit retardierter Wirkstofffreigabe (English shop)

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As pharmaceutical excipients, fats offer various advantages owing to their natural origin and their non-toxic properties. Nevertheless, they are used comparatively rarely in dosage forms. Their heterogeneous composition, poor characterisability and lack of stability as a result of ageing processes continue to pose major challenges.

The extrusion of fats in a twin-screw extruder below their melting temperatures represents an innovative manufacturing process in which fats can be processed into sustained-release matrices while largely retaining their structural and thermal properties.
Drug release from extruded fat matrices follows different release kinetics depending on the fat used. Embedding in fats with low HLB values leads to a sustained, predominantly diffusion-controlled release of the drug. The release rate is increased by raising the drug content and by using drugs with high solubility and/or small particle sizes.

The extrusion process allows drug particles to be embedded in fat extrudates with a comparatively small burst effect. This can be explained by a structural difference between extrudate surfaces and extrudate cross-sectional areas and is attributable to a specific arrangement of the drug particles within the matrix. These are arranged within the matrix in the flow during the extrusion step, with the formation of a smooth extrudate surface. As a result, the drug particles have only a small direct contact area with the extrudate surface, with the consequence that drug release from extrudate surfaces is slower than from the cross-sectional areas.

With a suitable choice of extrusion temperatures, it is possible to obtain low-porosity fat matrices based on glycerol trimyristate with efficient release retardation. Glycerol trimyristate was selected as an excipient because its structure is well defined and this fat crystallises rapidly in the stable modification. However, glycerol trimyristate can only be processed to a limited extent by pure melt processes, since after melting it crystallises into porous structures with an increase in volume. This can be avoided by extrusion below the melting range of glycerol trimyristate. Glycerol trimyristate extrudates have a low porosity and are biodegradable. They release the drug in a sustained manner over a period of about 16 hours, even in biorelevant media.
Glycerol trimyristate, which is already present in a stable, crystalline state as a powdered starting material, exhibits a stable solid state from the first minutes after extrusion onwards and shows stable drug release over nine months of storage at 40 °C.

Using a newly developed rounding process, the fat extrudates can be further processed into matrix pellets with sustained drug release. Under suitable process conditions, spherical pellets with aspect ratios below 1.1, equivalent diameters of about 1.5 mm and a narrow particle size distribution are obtained. The low material temperatures and the avoidance of solvents make the described process, consisting of extrusion and spheronisation, an interesting alternative for the production of sustained-release matrix pellets. These are well suited for use in multiparticulate dosage forms.