Impact of material properties and process parameters on tablet quality in a continuous direct compression line

The current paper shows how excipient properties impact the process parameters and the final tablet properties in a fully integrated continuous direct compression line. Blend properties of low-dose (1% w/w) and high-dose (40% w/w) paracetamol formulations were evaluated and linked to the blending and tableting performance via multivariate models (Partial Least Squares analysis, PLS). Feeding behavior was analyzed separately, as the amount of active pharmaceutical ingredient (API) that ended into tablets was driven by random fluctuations in the API feeding behavior. The developed PLS models elucidated that formulation behavior was mainly driven by the concentration of the active pharmaceutical ingredient (API), explained by the distinct API properties. Excipient properties also had a substantial impact on formulation behavior. Generally, formulations with microcrystalline cellulose as a filler showed better compactability, lower hold-up mass, lower flowability and higher cohesion than formulations with different lactose grades. The relative performance of a formulation with different fillers differed for 1% w/w and 40% w/w drug loading. Granular and spray dried lactose grades increased in compactability ranking compared to anhydrous lactose when evaluating higher drug loading, due to the difference in morphology. It was shown that besides understanding the impact of excipients on the formulation performance, processability of ingredients is crucial for formulation design.</p

Pectin-bioactive glass self-gelling, injectable composites with high antibacterial activity

The present work focuses on the development of novel injectable, self-gelling composite hydrogels based on two types of low esterified amidated pectins from citrus peels and apple pomace. Sol-gelderived, calcium-rich bioactive glass (BG) fillers in a particle form are applied as delivery vehicles for the release of Ca2+ ions to induce internal gelation of pectins. Composites were prepared by a relatively simple mixing technique, using 20% w/v BG particles of two different sizes (2.5 and <45 µm). Smaller particles accelerated pectin gelation slightly faster than bigger ones, which appears to result from the higher rate of Ca2+ ion release. µCT showed inhomogeneous distribution of the BG particles within the hydrogels. All composite hydrogels exhibited strong antibacterial activity against methicilin-resistant Staphylococcus aureus. The mineralization process of pectin-BG composite hydrogels occurred upon incubation in simulated body fluid for 28 days. In vitro studies demonstrated cytocompatibility of composite hydrogels with MC3T3-E1 osteoblastic cells

Novel injectable gellan gum hydrogel composites incorporating Zn- and Sr-enriched bioactive glass microparticles:high-resolution X-Ray micro-computed tomography, antibacterial and in vitro testing

Mineralization of hydrogel biomaterials is desirable to improve their suitability as materials for bone regeneration. In this study, gellan gum (GG) hydrogels were formed by simple mixing of GG solution with bioactive glass microparticles of 45S5 composition, leading to hydrogel formation by ion release from the amorphous bioactive glass microparticles. This resulted in novel injectable, self‐gelling composites of GG hydrogels containing 20% bioactive glass. Gelation occurred within 20 minutes. Composites containing the standard 45S5 bioactive glass preparation were markedly less stiff. X‐ray μCT proved to be a highly sensitive technique capable of detecting microparticles of diameter approximately 8 μm, i.e. individual microparticles, and accurately visualizing the size distribution of bioactive glass microparticles and their aggregates, and their distribution in GG hydrogels. The widely used melt‐derived 45S5 preparation served as a standard and was compared to a calcium‐rich, sol‐gel derived preparation (A2), as well as A2 enriched with zinc (A2Zn5) and strontium (A2Sr5).A2, A2Zn and A2Sr bioactive glass particles were more homogeneously dispersed in GG hydrogels than 45S5. Composites containing all four bioactive glass preparations exhibited antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA). Composites containing A2Zn5 and A2Sr5 bioactive glasses supported the adhesion and growth of osteoblast‐like cells and were considerably more cytocompatible than 45S5. All composites underwent mineralization with calcium‐deficient hydroxyapatite (CDHA) upon incubation in simulated body fluid (SBF). The extent of mineralization appeared to be greatest for composites containing A2Zn5 and 45S5. The results underline the importance of the choice of bioactive glass when preparing injectable, self‐gelling composites