Daniel Puckhaber1,2, Jan Henrik Finke1,2, Edgar John3, Michael Juhnke3, Arno Kwade1,2
1 Institute for Particle Technology, Technische Universität Braunschweig, Volkmaroder Straße 5, 38104 Braunschweig, Germany
2 Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, Franz-Liszt-Straße 35A, 38106 Braunschweig, Germany
3 Novartis Pharma AG, Basel 4002, Switzerland
The compaction of the majority of pharmaceutical formulations requires the addition of lubricants to prevent high ejection stresses during tablet production. Commonly applied lubricants comprise magnesium stearate (MgSt) and sodium stearyl fumarate whose internal addition to the formulation is often accompanied by unwanted changes of tablet properties, e.g. prolonged disintegration times and reduced tablet tensile strength. The latter can be explained by the coverage of particle surfaces with lubricants particles during preceding processes, e.g. mixing. This surface coverage weakens the interactions between the matrix-forming particles which results in a decrease of the tablet tensile strength. Tablets made of materials that have a limited ability to form new surfaces during compression, e.g. microcrystalline cellulose (MCC), are particularly sensitive to the loss of tensile strength.
This study focuses on quantitatively modeling the impact of MgSt on the compactibility of tablets consisting of different model materials. Therefore, binary mixtures consisting of diluents and lubricants were produced and compacted using a compaction simulator. The impact of formulation properties on the sensitivity to loss compactibility due to lubrication was investigated by applying different grades of diluents and MgSt which exhibited different bulk properties (e.g. particle size). Produced tablets were characterized according to their porosity and tensile strength and compactibility profiles were derived.
The developed model correlates the compactibility of lubricated diluents with the surface properties of the investigated formulation. Based on the equation of Ryshkewitch-Duckworth, a mathematical relationship between derived fit parameters and surface properties of applied lubricant/diluent particles was established [1]. Furthermore, the existing model was carefully extended to depict the impact of particle size and MgSt grade on compactibility by calculating the theoretical surface coverage. This finding allows the first cross-formulation description of compactibility reduction due to internal lubrication. Thus, the developed methodology displays a valuable tool for the development of new tablet formulations and should be further investigated for more complex powder mixtures to save time- and cost-intensive experiments.
[1] Puckhaber D., Finke J. H., David S., Serratoni M., Zafar U., John E., Juhnke M., Kwade A., 2022, Prediction of the impact of lubrication on tablet compactibility, International Journal of Pharmaceutics, Volume 617
Jan Henrik Finke, Pharmacist, received his doctor’s degree in pharmaceutical technology (microfluidic production of colloidal drug delivery systems) from the TU Braunschweig, Germany, in 2014. Since 2013 he is heading the working group for Pharmaceutical Process Engineering which later developed into the Division of Pharma and Bioparticle Technology at the Institute for Particle Technology. He focusses on solid dosage form development and manufacturing processes, also taking production of (drug/delivery system) nanoparticles and downstreaming these and living microorganisms from suspensions to dry formulations.
Daniel Puckhaber has Master of Science in Pharmaceutical Engineering from Technische Universität Braunschweig. He is currently a research Associate at Technische Universität Braunschweig in the Institute for Particle Technology Bio- and Pharmaparticle Engineering.
You must be logged in to post a comment.