Publications | Daan Zillen

Combinations of arginine and pullulan reveal the selective effect of stabilization mechanisms on different lyophilized proteins

Khanh T. T. Nguyen¹, Daan Zillen¹, Alessia Lasorsa, Patrick C.A. van der Wel, Henderik W. Frijlink, Wouter L. J. Hinrichs ¹These authors contributed equally to this work The stability of lactate dehydrogenase (LDH) and β-galactosidase (β-gal), incorporated in arginine/pullulan (A/P) mixtures at various weight ratios by lyophilization, was determined. The physicochemical characteristics of various A/P mixtures were assessed. With decreasing A/P ratios, the glass transition temperature of the formulations increased. Furthermore, arginine crystallization due to high relative humidity (RH) exposure was prevented at an A/P weight ratio of 4/6 or less....

Surface Engineering Methods for Powder Bed Printed Tablets to Optimize External Smoothness and Facilitate the Application of Different Coatings

Khanh T. T. Nguyen, Daan Zillen, Franca F. M. van Heijningen, Kjeld J. C. van Bommel, Renz J. van Ee, Henderik W. Frijlink and Wouter L. J. Hinrichs In a previous attempt to achieve ileo-colonic targeting of bovine intestinal alkaline phosphatase (BIAP), we applied a pH-dependent coating, the ColoPulse coating, directly on powder bed printed (PBP) tablets. However, the high surface roughness necessitated an additional sub-coating layer. In this study, we aimed to find a production method for PBP tablets containing BIAP that allows the direct application of coating systems....

Formulation of a 3D Printed Biopharmaceutical: The Development of an Alkaline Phosphatase Containing Tablet with Ileo-Colonic Release Profile to Treat Ulcerative Colitis

Khanh T. T. Nguyen, Franca F. M. Heijningen, Daan Zillen, Kjeld J. C. van Bommel, Renz J. van Ee, Henderik W. Frijlink and Wouter L. J. Hinrichs Powder bed printing is a 3D-printing process that creates freeform geometries from powders, with increasing traction for personalized medicine potential. Little is known about its applications for biopharmaceuticals. In this study, the production of tablets containing alkaline phosphatase using powder bed printing for the potential treatment of ulcerative colitis (UC) was investigated, as was the coating of these tablets to obtain ileo-colonic targeting....

Natural and bioinspired excipients for dry powder inhalation formulations

Daan Zillen¹, Max Beugeling¹, Wouter L. J. Hinrichs, Henderik W. Frijlink and Floris Grasmeijer ¹These authors contributed equally to this work Pulmonary drug delivery can have several advantages over other administration routes, in particular when using dry powder formulations. Such dry powder inhalation formulations generally include natural and bio-inspired excipients, which, among other purposes, are used to improve dosing reproducibility and aerosolization performance. Amino acids can enhance powder dispersibility and provide protection against moisture uptake....

Impact of malnourishment on the pharmacokinetics of acetaminophen and susceptibility to acetaminophen hepatotoxicity

Daan Zillen, Kris L. L. Movig, Gert Kant, Joost B. Masselink, Paola Mian Background: Acetaminophen hepatotoxicity is thought to be primarily caused by formation of the specific reactive metabolite N-acetyl-para-benzo-quinone imine (NAPQI). Malnourished individuals are at increased risk of acetaminophen-related hepatotoxicity. We report a case of low acetaminophen clearance in a severely underweight young woman, and elaborate on the possible effects of malnutrition on the total clearance of acetaminophen as well as on the separate contributions of the different metabolic pathways....