Mechanism and characterization of eutectic formation upon compaction and its effects on tablet properties

The broad objective of this research was to investigate the effects of eutectic formation during compaction on tablet properties. The specific aims were to study the mechanism of eutectic formation upon compaction, develop analytical methods to quantify the amount of eutectics formed in the tablets, and determine the eutectic effects on tablet properties. It was hypothesized that eutectic formation is a function of the pressure-induced increases in the area and intimacy of contact (close inter-particulate distance) between the eutectic-forming components. Formation of eutectics in tableted dosage forms may, therefore, not require the eutectic temperature to be exceeded during manufacturing as is generally believed, but rather the mixture may form due to mechanical stress, which facilitates the intimate contact between the eutectic-forming materials. A thermodynamic/heat transfer approach was used to explain the mechanism of eutectic formation upon compaction, and a differential scanning calorimetric (DSC) method was developed to detect and quantify the amount of eutectic formed in the tablets. The results show that eutectic melting or contact melting is an entropy-driven phenomenon. The criteria of a eutectic formation are that the eutectic-forming compounds need to be in intimate contact in solid state and mutually soluble in each other in the liquid state. Some eutectics are, therefore, formed when a uniform physical mixture of eutectic-forming compounds is compacted. The amount of eutectic formed in the tablets quantified by the DSC method developed is a function of compaction force. The intimate contact area between eutectic-forming materials in the tablets as a function of compaction force was estimated and calculated. The correlations of the amount of eutectic formed with the estimated and calculated contact area support the concept that mechanically induced contact can cause eutectic behavior equivalent to that observed in eutectics formed by fusion. This study also showed that eutectic has no negative effect on tablet hardness. The models and concepts developed to estimate the impact of the processing conditions on eutectic formation may serve as a guide during materials science and process development studies to anticipate any undesired eutectic formation