Gabriel M. H. Meesters

Breakage behaviour of enzyme granules in a repeated impact test

Abstract In many industries, handling or processing of relatively fragile particles takes place and predictions are required whether a significant proportion of the particles will be damaged. These processes have been designed and controlled solely on the basis of particle size and shape. Another parameter that needs to be introduced is particle strength. The stringent environmental laws demand improved particle mechanical quality, which has given rise to the need for a more accurate and fundamental particle strength measurement and its application in modelling and control of particulate processes. Particles need to show good resistance against static and dynamic loads. The present paper deals with the study of breakage behaviour of different enzyme granules subjected to repeated impacts using a new instrument developed at the Delft University of Technology. The impact test involves bombarding the particles against a flat target repeatedly. The main feature of this new test is its ability to impact a large number of particles against a flat target repeatedly, and generate extremely reproducible results. Testing a large number of particles has the advantage of producing statistically correct results. The repeated impacts provide information on the breakage behaviour of the particles based on their history. In the new impact test enzyme granules can undergo very low impact velocities of the order of 5 m s−1. These low impact velocities lead to attrition and chipping of the granules. The current paper presents preliminary results on the breakage behaviour of the new impact test and its basic advantages over already existing tests. Furthermore, experiments were performed on enzyme granules, and the breakage mechanisms determined, depending on the change in size and shape of the particles.

Gas-Phase Deposition of Ultrathin Aluminium Oxide Films on Nanoparticles at Ambient Conditions

We have deposited aluminium oxide films by atomic layer deposition on titanium oxide nanoparticles in a fluidized bed reactor at 27 ± 3 °C and atmospheric pressure. Working at room temperature allows the coating of heat-sensitive materials, while working at atmospheric pressure would simplify the scale-up of this process. We performed 4, 7 and 15 cycles by dosing a predefined amount of precursors, i.e., trimethyl aluminium and water. We obtained a growth per cycle of 0.14–0.15 nm determined by transmission electron microscopy (TEM), similar to atomic layer deposition (ALD) experiments at a few millibars and ~180 °C. We also increased the amount of precursors dosed by a factor of 2, 4 and 6 compared to the base case, maintaining the same purging time. The growth per cycle (GPC) increased, although not linearly, with the dosing time. In addition, we performed an experiment at 170 °C and 1 bar using the dosing times increased by factor 6, and obtained a growth per cycle of 0.16 nm. These results were verified with elemental analysis, which showed a good agreement with the results from TEM pictures. Thermal gravimetric analysis (TGA) showed a negligible amount of unreacted molecules inside the alumina films. Overall, the dosage of the precursors is crucial to control precisely the growth of the alumina films at atmospheric pressure and room temperature. Dosing excess precursor induces a chemical vapour deposition type of growth due to the physisorption of molecules on the particles, but this can be avoided by working at high temperatures.

Formulation and antifungal performance of natamycin-loaded liposomal suspensions: the benefits of sterol-enrichment.

Abstract The aim of this study is to develop and evaluate food-grade liposomal delivery systems for the antifungal compound natamycin. Liposomes made of various soybean lecithins are prepared by solvent injection, leading to small unilamellar vesicles (<130u2009nm) with controlled polydispersity, able to encapsulate natamycin without significant modification of their size characteristics. Presence of charged phospholipids and reduced content of phosphatidylcholine in the lecithin mixture are found to be beneficial for natamycin encapsulation, indicating electrostatic interactions of the preservative with the polar head of the phospholipids. The chemical instability of natamycin upon storage in these formulations is however significant and proves that uncontrolled leakage out of the liposomes occurs. Efficient prevention of natamycin degradation is obtained by incorporation of sterols (cholesterol, ergosterol) in the lipid mixture and is linked to higher entrapment levels and reduced permeability of the phospholipid membrane provided by the ordering effect of sterols. Comparable action of ergosterol is observed at concentrations 2.5-fold lower than cholesterol and attributed to a preferential interaction of natamycin–ergosterol as well as a higher control of membrane permeability. Fine-tuning of sterol concentration allows preparation of liposomal suspensions presenting modulated in vitro release kinetics rates and enhanced antifungal activity against the model yeast Saccharomyces cerevisiae.

Amorphous APIs: Improved Release, Preparation, Characterization

Producing Amorphous Active Pharmaceutical Ingredients offers an enhanced drug release that is caused by the increase in its dissolution rate. This improvement enables higher bioavailability and bioactivity of such solid APIs. Possibilities to control the drug release and its bioactivity offer new opportunities to design more effective and stable medications. This chapter is a general introduction to Amorphous APIs and most commonly discussed production and characterization methods.