Characterization of functionalized calcium carbonate as a new pharmaceutical excipient

摘要

Excipients are indispensable functional components, which are used to develop innovative, robust,udand reproducible formulations with good patient compliance due to optimized plasma concentrationsudand less side effects. Nowadays, new excipients have to show a multifunctionality in order toudbe used for unique applications that are not feasible with existing excipients. This multifunctionalityudcan be achieved by co-processing excipients, where undesirable properties of an excipient areudmasked, favorable attributes are retained, and new properties supplement the substance.udThe main aim of this thesis was to map the applicability of such a co-processed novel excipient,udFCC, in the field of pharmaceutical technology.udThe results of the mechanistic study showed that the attributes of FCC present a striking successudin the field of excipient research. FCC-based tablet formulations had mechanical properties equaludor superior to those of conventionally used excipients such as microcrystalline cellulose (MCC),udmannitol, or calcium carbonate. FCC tablets with high tensile strength and high porosity wereudobtained already at low compressive pressures. The key factor for the outstanding performanceudof FCC was the lamellar structure of the particle, which formed a porous meshwork (intraparticleudporosity), resulting in a high specific surface area available for particle bonding.udThe limitations of poor flowability and high bulk density of FCC powder during direct compressionudwere overcome by granulation. FCC granules prepared by roller compaction showed excellentudflowability and reduced bulk volume, whereas all the outstanding properties of the powder, such asudcompactability and compressibility, were preserved. The dry granulation process converted FCCudinto a suitable form for scale-up processes on high-throughput tablet presses. Roller compaction isudthe process of choice if porosity and high surface area of FCC particles have to be preserved duringudgranulation process.udOn the examplary model of direct compressed ODTs, the applicability of FCC was investigated.udODTs containing FCC were produced by direct compression. Owing to the lamellar structure, FCCudwas able to overcome the limitation of insufficient hardness during the production of highly porousudODTs. These findings could revolutionize the production of ODTs and hence open up new vistas.udTo protect the valuable findings, a patent was applied for the production of ODTs made of FCC.udThe characterization of co-processed FCC revealed a promising new pharmaceutical excipient with audbroad range of applicability. Applicability of FCC seems to be of particular interest for formulationsudthat are characterized by high porosity, high tensile strength, or both. This is the case, amongstudothers, for ODTs, carriers, adsorbents, floating tablets, effervescent tablets, controlled-releasedudformulations, ultra hard tablet (UHT), and cushioning agents.