Non-Contact Drug Tablet Monitoring
Various methods of drug tablet monitoring have been introduced over the years for process monitoring purposes. Non-invasive techniques, such as acoustic emission (AE), have been widely used in the pharmaceutical industry for monitoring granular materials. By measuring AE it is possible to identify many of the phenomena that occur during powder compaction of pharmaceutical products, such as gran...
Various methods of drug tablet monitoring have been introduced over the years for process monitoring purposes. Non-invasive techniques, such as acoustic emission (AE), have been widely used in the pharmaceutical industry for monitoring granular materials. By measuring AE it is possible to identify many of the phenomena that occur during powder compaction of pharmaceutical products, such as granular rearrangement, fragmentation, visco-plastic deformation of grains or granules. Acoustic relaxation emissions are detected and utilized during roller compaction of microcrystalline cellulose and maize starch.
Any change in the mechanical properties of a tablet produces a shift in the resonant frequencies, allowing a novel acoustic technique for inspecting tablets that combines air-coupled excitation and laser interferometric detection. This technique offers non-contact measurement of acoustic waves at the surface of a sample—giving it a clear advantage over other methods when rapid measurements are required (such as on a production line) and/or at a large number of points, such as in batch processing.
Main components in the experimental setup consist of a square-wave pulser/receiver (Panametrics 5077PR), a 1 MHz air-coupled transducer (VN Instruments CAP 5), a laser interferometer (Polytec OFV 511), and a digitizing phosphor oscilloscope (Tektronix TDS 3052). Since the tablet would either be rigidly held or freely standing during batch processing, two different acoustic experimental setups were proposed and tested on sample tablets:
Rigged tablet setup. The schematic instrumentation diagram used in the rigged tablet experimental investigation is depicted in 'Rigged tablet acoustic set-up' graphic. The aluminum rig holder rigidly holds the sample tablet. The air-coupled transducer is placed on the side of the sample tablet (shown in photo). The laser interferometer is placed directly above the sample tablet, and the laser beam is properly focused on the tablet surface.
Free-standing tablet setup. Schematic instrumentation diagram for the freestanding experimental setup is depicted in the graphic. The sample tablet is freely placed on an aluminum base. The air-coupled transducer is placed directly above the sample tablet (at a height of approximately 4 mm from the tablet's top surface). The laser interferometer is kept on the side of the tablet, and the laser beam is properly focused at a point on the tablet surface. This setup can be used in batch processing when a conveyor transports the tablet from one stage of the manufacturing process to another.
Using the proposed non-contact excitation and measurement setup, a series of acoustic based non-contact experiments were conducted to study mechanical properties of the sample drug P-tablet (P-tablet mesh model graphic). The transverse vibrational response of the tablet is determined at two locations (the tablet surface center and a random off-center location on the tablet surface) in both experimental setups (rigged and free-standing) for the samples. For each sample tablet, four sets of measurements are taken at one location; 16 sets of measurements are obtained for testing the repeatability and stability of the experimental set-ups.
Schematic diagram shows the rigged tablet acoustic-setup.
The pulser/receiver provides a square pulse to the transmitting air-coupled transducer. The acoustic field excited by the transmitting air-coupled transducer interacts and vibrates the sample tablet. Laser detection of the surface vibrational response of the sample tablet is accomplished with the laser interferometer. The interferometer used in this study makes high-fidelity and absolute measurements of surface displacement over a bandwidth of 50-30 MHz, and it is possible to detect the displacement with nanometer resolution. The measured response is digitized by the oscilloscope and used for signal processing.
Two signal processing methods, namely deconvolution and system identification, are applied to the measured transient surface displacement response of the sample tablet to extract the resonant frequencies of the vibrating tablets. The main utility of these two methods is to obtain the impulse response of drug tablet alone by separating the transducer response from the tablet response. The frequency domain response provides the resonant frequencies of drug tablet that are related to the tablet's mechanical hardness and density.
Numerical predictions of the tablet's resonant frequencies by finite element (FE) method are used to verify experimental data. In the finite element study using the Abaqus commercial package, it is assumed that the sample tablet (P-tablet) is a homogenous and isotropic elastic-solid with no coating. Uniform meshes of four-node linear tetrahedron elements are generated for the sample tablet. Lanczos eigenvalue solver is employed to calculate resonant frequencies of both sample tablets in the frequency range of 50 kHz to 200 kHz.
The meshed sample P-tablet 11.71 mm long, 6.01 mm wide, and 3.84 mm thick is depicted in P-tablet graphic. The 180-m long mesh of tablets has 127,311 elements and 74,196 degrees of freedom. Resonant frequencies of P-tablet from the FE data are obtained.
P-tablets are examined in the two experimental setups to determine the resonant frequencies of a rigged tablet and a freestanding tablet. Vibrational response in the time-domain for the rigged tablet setup on excitation with the air-coupled transducer is depicted in 'Surface displacement response' graphic. Note that the multiple measurements for the sample tablets are in agreement. Consistent time domain responses imply that the air-coupled excitation and interferometric detection is repeatable and stable.
Charting of the transient surface displacement responses of A-tablet in the rigged setup.
'Vibrational response frequency spectra' graphic depicts the frequency spectra of the P-tablet. Resonant frequencies of the sample tablet are consistent. Experimental results present high consistency and repeatability as shown in time and frequency domains. To increase confidence in experimental measurement accuracy, numerical results and experimental results are compared. Agreement exists between the experimentally obtained results and the numerical results, especially within the frequency range of 130 -200 kHz.
Experimental results using Method 1 show a greater degree of correlation to the numerical data than Method 2; each experimental case shows the compromise of added frequencies.
From numerical and experimental data and their comparisons, the frequency measurements from both experimental setups are consistent and can be considered effective for determining resonant frequencies of a drug tablet.
The non-parameter system estimation technique (Method 2) is found to give a better estimation of the dominant vibration components of the responses than Method 1, whereas the deconvolution technique (Method 1) provides more resonance frequencies from the experimental data. Cross-correlation data show that Method 1 exhibits clearer similarity to the numerical results than Method 2 for different drug tablets.
This acoustic technique of air-coupled excitation and laser interferometric sensing can be incorporated at different stages of the batch processing in the pharmaceutical industry. The rigged setup can be used when a pick-and-place mechanism rigidly holds the tablet, while the free-standing setup can be used when the tablet is transported on a conveyor belt.
This article originally appeared in Pharmaceutical Processing ; www.pharmpro.com
Ajaz S. Hussain and et al., Foreword, Journal of Process Analytical Technology, Vol.1, No.1, 3 (2004)
E. Serris and et al., Acoustic Emission of Pharmaceutical Powders During Compaction, Powder Technology 128, No.2-3, 296-299 (Dec. 18, 2002)
J. Salonen and et al., Monitoring the Acoustic Activity of a Pharmaceutical Powder During Roller Compaction, International Journal of Pharmaceutics 153, No.2, 257-261 (July 30 1997)
C. B. Scruby and L. E. Drain, “Laser Ultrasonics: Techniques and Applications,” Adam Hilger, 1990
I. Varghese, M.S. Thesis, “Laser Acoustic Techniques for Drug Tablet Monitoring,” Clarkson University, 2004
I. Varghese, L. Ban, M. D. M. Peri, C. Li, G. Subramanian and C. Cetinkaya, Dept. of Mechanical and Aeronautical Engineering, Center for Advanced Materials Processing, Wallace H. Coulter School of Engineering, Clarkson University Potsdam, NY
- Events & Awards
- Magazine Archives
- Digital Reports
- Global SI Database
- Oil & Gas Engineering
- Survey Prize Winners
- CFE Edu