(95ad) Correlation Study between Liquid Penetration and Mechanical Properties of Pharmaceutical Tablets

Authors: 
Tomas, J., University of Chemistry and Technology
Dvorak, 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
Main phenomenon influencing treatment of patient in pharmacy is amount of active pharmaceutical ingredient dissolved in medium such as water or blood. Even though this isa key step to achieve desirable medical effect it is not the first one occurring.The first step is governed by surface properties such as wettability and roughness and the first contact point is followed by liquid penetration which is highly dependent not onlyon type of used liquid, ionstrength, liquid density but also on mechanical and structural properties of tablets such as porosity, structure strength or particle bonds.Through many analytical methods we can describe each of thesesteps individually. Aim of this study is to find proper correlation amongseveralmethods such as sessile drop method, texture analysis (TA) and magnetic resonance imaging (MRI) of tablet during dissolution.

For experiments binary mixture of tabletwas used. Tablets consist of lactose (hydrophilic) and ibuprofen (hydrophobic)with variable content (from 0.2 to 0.5 w/w ratio) and were also variable in compaction pressure used on them (from low – 5 kN through 10kN as middle to 18 kN as high).Three different solutions were used according to their saturation with primary substances to prevent the tablet from dissolving. Surface properties were evaluated on contact angle and soaking rate of liquid, both measured by sessile drop method. Texture analysis was performed by recording the material resistance during dry and wet state of tablet. Then the data was processed and trends were obtained.Tablets during the MRI experiments were submerged into dissolution medium and the proceeding wetting front was measured. Later the images were processed via image analysis and trends were obtained.

Results obtained from surface experiments show that higher the ibuprofen content is the more hydrophobic surface appears to be and therefore the contact angle is increasing. Contact angle is independent on manufacturing pressure but soaking rate on the other hand depends strongly.MRI images show that this technique is not suitable for rapidly disintegration tablets, where the calculated error is within experiment conditions. On the other hand, tablet with prolonged dissolution are well measured. Results from MRI experiments also state that local saturation with substances supress dissolution of tablet. Texture analysis of tablets show that they undergo immediately structural weakening after being poured with solution independently on type of solution. Rate of this structural change mainly depends on solution's acidity. Thenthe tablet decreases its resistance in time which can be interpreted as relaxation rate. With increment of ibuprofen or saturation with primary substances this rate decrease, which means that dissolution is suppressed. Correlation between MRI and relaxation rate was done. Results shows that the correlation is mainly dependent on texture analysis measurement. On the other hand, correlation between MRI and soaking rate appears to be more tentative.

Experiment characterising surface, structural and liquid penetration properties were investigated by three different techniques. Obtained results were evaluated and put to mutual correlation. From liquid penetration point of interest there is correlation between MRI and contact angle method. Also, a correlation between MRI and texture analyser was found.