Power consumption measurement and temperature recording during granulation.

This study was performed to elucidate the influences of process and formulation design using power consumption and temperature measurements during granulation. Power consumption was recorded "in process" using a previously introduced computer program for optimal end-point detection at an early stage. The temperature increase (DeltaT) during granulation was recorded using a temperature sensor. The temperature increase in the wet powder bed expresses the friction forces at interparticle contacts occurring during granulation. The maxima of temperature profile occurred at 130% saturation, whereas the maxima of power consumption were determined at 100% saturation. The ratio of temperature and power consumption (TPR factor) is introduced as a signature of formulation design. TPR factor was found to be dependent on particle size, particle surface, water absorption capacity and solubility of the excipient and model drug, respectively. However, TPR factor was found to be independent of process design, such as the filling level of the mixer. Understanding and controlling the granulation process is a key factor in robust dosage form design. The "in process" control fits ideally the prerequisites of a drug quality system for the 21st century and FDA's Process Analytical Technology (PAT) initiative. The results of previous and present works of our research group will be used in a following step to develop an artificial neural network for granulation "in process" control.

Power consumption profile analysis and tensile strength measurements during moist agglomeration.

This study was performed to elucidate the influences of process and formulation design on the granulation process using power consumption and tensile strength measurements. In order to record and analyze the power consumption profile "in process" a computer program was developed to be used for optimal end-point control in reproducible granule production. The program analyzes and calculates a characteristical point, the turning point of the S-shaped ascent of the profile. The tensile strength expresses the cohesiveness between the powder particles, which is dependent on saturation and capillary pressure. In order to investigate the influence of the amount of liquid present in the granular material on tensile strength a device was developed. The maxima of tensile strength occurred at 90% saturation, whereas the maxima of power consumption were determined at 100% saturation. The measured tensile strength sigma (N/m(2)) equals to the volume specific cohesion (J/m(3)). The present work proved that the power consumption measurement is an alternative, simple and inexpensive method to determine the cohesion of powder particles. The turning point is introduced as a signature of the starting material and furthermore as a parameter for the cohesiveness of the starting material and therefore for optimal end-point detection at an early stage.