# Tablet Evaluation Using Ultrasound Transmission Measurement

## Ultrasound can be a useful PAT tool for evaluating the tensile strength of tablets

The mechanical properties of tablets are important because they are related to their therapeutic response. Tablets have to be hard enough for later process stages such as coating and storage. Mechanical failures can originate from the compaction process as well. Known as capping and lamination, these issues can cause tablets to break during coating and packing and cause serious problems during the manufacturing process.

Traditionally, the mechanical properties of tablets have been determined using destructive test methods such as diametrical and bending tests. However, it’s been reported that the diametrical test method has its own limitations, providing an estimation of the crushing force of tablets.1 Because tablet hardness and capping and lamination issues are related to the mechanical properties of tablets, ultrasound (a commonly used test method used to determine the mec hanical properties of test samples in different kinds of non-destructive testing applications) may be a useful tool for the non-destructive evaluation of tablets.

Ultrasound is a mechanical wave with a frequency higher than 20 kHz. In a medium, ultrasound waves propagate at the speed of sound. Ultrasound is generated using a transducer that normally transmits a pulse with a finite length. In addition, the pulse has a nominal center frequency. An example of an ultrasound pulse and its frequency spectrum is shown in Figure 1. An ultrasound pulse is generated via the pulser/receiver unit and the waveform is acquired using an oscilloscope.

The speed of sound of the material under investigation is calculated using the thickness of the sample and a time-of-flight value obtained simply by dividing the sample’s thickness measurement with the time-of-flight value. The time-of-flight value is determined from a measured ultrasound signal and the time that it takes for the wave to travel through a given medium. In this study, time-of-flight was determined using the maximum value of the transmitted ultrasound signal.2 The maximum value of the ultrasound signal is obtained using the pulse envelope calculated using the Hilbert transformation and the corresponding time instant is the time-of-flight value (Figure 1).

During its propagation through a medium, the ultrasound wave will be subject to the energy loss caused by absorption and scattering. The attenuation coefficient is a measure of these losses.3 The ultrasound attenuation coefficient value tells how much the signal attenuates per length, and it is normally given in dB/cm. The frequency-dependent attenuation coefficient “a” is calculated using the equation3:

a(f) =

Where h is the thickness of a tablet, A is the frequency spectrum of the ultrasound signal measured from the tablet; Aref is the frequency spectrum of the ultrasound signal measured from the reference sample (stainless steel in this study). The frequency spectrum of a signal is calculated using the Fourier transformation. In addition, the thickness of the tablet is used in the calculation of the ultrasound attenuation.

**TENSILE STRENGTH EVALUATION**

Two commonly used pharmaceutical excipient powders, microcrystalline cellulose (MCC) Avicel PH101 and dibasic calcium phosphate dehydrate (DCP) were used to compress tablets with only one ingredient. The powders were used as received. Before compaction, a helium pycnometer was used to measure the apparent particle density resulting 1.5307 g/cm3 and 2.380 g/cm3 for MCC and DCP, respectively. Tablets were directly compressed using a compaction simulator with 10 mm, flat-faced punches. The compaction profile was a single-sided triangle for the upper punch and a stationary lower punch. Tablet weight was set at 350 mg for all the tablets, but five different compression force values were used to compress test samples to produce tablets with different tensile strengths. Each compression force value had 10 parallel samples, so for both excipient s a total number of 50 tablets were produced.

The ultrasound measurements were made using a measurement set-up shown in Figure 2. The speed of sound was measured using a pair of 10-MHz contact ultrasound transducers. The tablet was placed between the transducers and a force of 12 N was applied to ensure proper acoustical coupling between the transducers and the tablet. The speed-of-sound values were calculated using the measured time-of-flight value and the thickness of the tablet. After the ultrasound measurements, the crushing force of the tablet F was determined using a mechanical tester and the tensile strength values were calculated using the equation4

a = 2F/(nDh)

where D and h are the diameter and the height of the tablet, respectively.

As shown in Table 1, the speed of sound increases with the tensile strength of tablets. Next, statistical tests were made to investigate the relationship between the speed of sound and tensile strength values. The speed of sound values were divided in five groups (see Table 1) and the statistical difference between the groups was tested using the Mann-Whitney U-test. As a result, all groups are statistically different from each other (p<0.05) for both MCC and DCP tablets. To visualize this relationship, the speed of sound is plotted as a function of the tensile strength (Figure 3). As shown in Figure 3, the speed of sound is linearly increasing with the tensile strength. The calculation of the correlation coefficient between the speed of sound and tensile strength yielded the values of r2= 0.9972 and r2= 0.9949 for MCC and DCP, respectively.

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