Various fillers/binders which are applied for the formulation of solid oral dosage forms are assessed for their benefits and drawbacks, including lactose, sorbitol, mannitol, microcrystalline cellulose and calcium hydrogen phosphate dihydrate. A focus of this work was to evaluate the application of mannitol in comparison to other common fillers/binders as it was observed that this excipient is gaining more and more attention in pharmaceutical formulation development and production. While one of the main advantages of conventional fillers/binders such as lactose, microcrystalline cellulose and calcium hydrogen phosphate dihydrate is their low price level, mannitol excels regarding its physicochemical characteristics such as a low hygroscopicity, a strong inertness towards both the API and the patient's body, its good compactibility and the ability to produce extremely robust tablets. Additionally, the suitability of mannitol for the emerging formulation technology of orally disintegrating tablets is pointed out. In summary, it is emphasized that the selection of the filler/binder is highly individual, depending, for example, on the preferred characteristics of the final solid dosage form, the applied API and the available budget. However, mannitol exhibits many strong advantages which can be expected to result in a more widespread application in the near future.

The inhibitory effects of DHA on Gluconobacter oxydans were measured to forrmulate a fermentation model. Growth of Gluconobacter oxydans is inhibited by DHA which can be modelled by a linear Term. The inhibition of product formation by DHA was measured and described by a classical feedback inhibition kinetic. Additionally, an irreversible destruction of Gluconobacter cells by DHA was discovered. This toxic effect of DHA could be modelled by a death rate kinetic and introduction of a damaged cell type. DHA also inhibits the activity of the pentose cycle as can be measured via the CO, evolution rate.

The influence of culture pH on the metabolism of Gluconobacter oxydans was determined. An acidic milieu during growth of the organism enhances the oxidation rate. The CO 2 evolution rate representing the assimilation of the product is inhibited by a low pH value. Growth of the bacteria is possible both on glycerol and DHA in separate phases, which is not a controlled as diauxic growth. Product formation follows Luedeking-Piret kinetics.

The inhibitory effects of glycerol on Glucorwbacter oxydans were measured separately. The kinetics of oxygen uptake rate representing the DHA production, the CO, evolution rate representing the assimilation of the product, and the specific growth rate were mathematically modelled. Glycerol does not inhibit DHA formation and CO,-evolution.

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