(51b) Tablet Disintegration: Advanced Methodology Development

Authors: 
Dvorak, J., University of Chemistry and Technology
Lizonova, D., Department of Chemical Engineering, University of Chemistry and Technology
Tomas, J., University of Chemistry and Technology
Schongut, M., University of Chemistry and Technology
Stepanek, F., University of Chemistry and Technology
Beranek, J., Zentiva k.s., a Sanofi Group company
Dammer, O., Zentiva k.s., a Sanofi Group company
Nowadays, most of the drugs are introduced into the organism in the form of orally administered tablets. It is commonly known that composition, excipients and manufacturing process significantly affect behaviour of the tablets when exposed to aqueous media. significantly affect behaviour of the tablets when exposed to aqueous media. There is a big effort to quantitively and qualitatively describe disintegration, using techniques such as UV-VIS imaging, terahertz time-domain spectroscopy or Raman spectroscopy. In the presented work, there is an overview of used techniques to describe disintegration on binary model tablets made of mixture of ibuprofen and lactose (content of ibuprofen from 0.2 to 0.5 w/w), prepared at different compaction pressures (low, medium and high) are subjected the tests, which should help to identify their dissolution behaviour, mechanical and surface properties, wettability or liquid penetration.

Certified dissolution tests showed that the composition is significant in the most cases (there is a step change in dissolution times between 0.2/0.3 and 0.4/0.5 w/w). Further testing in aqueous environment revealed that there are some properties that are dependent on both composition and compaction pressure.

Measurements by sessile drop method provided information about soaking time and contact angle. Contact angle experiments shows surface tendency to get more hydrophobic with ibuprofen increment. This fact also has minor role in soaking time of liquid to tablet, where major influence is done by manufacturing pressure and thus porosity of tablet.

Experiments based on Texture Analysis exploring the structural properties showed dependence both on compaction pressure and composition as well as on used solution. Acidity plays significant role in tablet strength when there is risk of side reaction with excipient. Overall structure weakening was observed independently on used solution.

Magnetic Resonance Imaging was used for quasi-online monitoring of tablet behaviour in different solution. From experiment can be shown that both higher ibuprofen content and higher compaction pressure slows down disintegration and dissolution processes as well as local saturation of component in solution. There is a surface erosion of tablet observed, when exposed to dissolution medium. Through MRI it can be observed different tablet behaviour such as laminating, disintegration to clusters or dissolution of whole tablet.

The roughness of the tablet surface depends only on the composition and can be evaluated via Scanning Electron Microscopy and subsequent image analysis. Image analysis showed progressive lactose washing out with revealing ibuprofen crystals.

Chemical composition of the tablets can be determined using FTIR microscopy or imaging, where not only the amount but also the morphology of the primary particles on the tablet`s surface can be detected. The size of the primary ibuprofen particles was determined and the differences between two ibuprofen suppliers were clearly detected.

Dissolution and disintegration tests in discriminative conditions showed significant decrease in dissolution rate of ibuprofen, when lactose dissolution was prevented. However, there is an interesting discovery that the tablets with 0.2 w/w ibuprofen are disintegrating also in the case when neither component is dissolving.

These findings lead to the idea of the disintegration can be driven by affinity of the hydrophobic substance to the solvent, which facilitates water penetration and subsequent disintegration and that disintegration occurs due to weakening of inter-particle forces in presence of solution.