(424c) Real Time Prediction of Tablet Tensile Strength By Ultrasound in Continuous Manufacturing

Tablet tensile strength is a critical property that needs to be well controlled in order to produce an acceptable pharmaceutical product. Methods that allow real time and non-destructive prediction of tablet properties can greatly help the development efforts in a continuous manufacturing line. Real-time measurement of tablet strength by ultrasound increases assurance of product quality and is economically beneficial in continuous manufacturing. A model for predicting tablet strength by ultrasound will enable rapid techniques in continuous assessment of tablets ensuring the desired quality attributes.

The objective of this research project was to develop a statistical model to predict tablet tensile strength in a direct compaction continuous manufacturing line. Tablets consisted of model API, Acetaminophen (APAP), lactose monohydrate as the filler, and magnesium stearate as lubricant. Multivariate effects were analyzed using Quality-by-Design methods. The experiment was based on a fractional factorial design with 30 experiments, including 3 repeated center points, to study the influence of four process variables â?? drug concentration (%), compaction force (KN), blending speed (rpm), and feed frame speed (rpm) â?? on the final product. Ultrasound transmission speed was determined by measuring the sound wave time-of-flight (TOF) using transducers with a frequency of 2.25 MHz. The speed of sound (SOS) was calculated by dividing the measured tablet thickness by the TOF. The same tablets were characterized for diametrical crushing strength using a mechanical hardness tester. The ANOVA results indicated that compaction force was the main parameter affecting tensile strength and SOS of the tablets in this process. However, ultrasound was sensitive to drug concentration and feed frame speed. Therefore, a predictive model was developed to correlate tensile strength with SOS and relative density. The model was verified using an independently manufactured validation set. The predicted values obtained from the model were in agreement with the experimental results with a correlation coefficient of 0.92. It was further concluded that by using the ultrasound measurement technique it is possible to assess the quality characteristics of tablets non-destructively and in real time.