Non-Contact Acoustic Techniques for Drug Tablet Monitoring

Abstract

Quality assurance monitoring and material characterization is of great importance in the pharmaceutical industry. If the tablet coating and/or core are defective, the desired dose delivery and bioavailability can be compromised. Tablet coatings serve a wide variety of purposes such as regulating controlled release of active ingredients in the body, contributing to the bioavailability of a particular drug or combination of drugs, during certain times and locations within the body, protecting the stomach from high concentrations of active ingredients, extending the shelf life by protecting the ingredients from degradation from moisture and oxygen, and improving the tablet's visual appeal. If a coating layer is non-uniform and/or contains surface or sub-surface defects, the desired dose delivery and bioavailability can be compromised. The Food and Drug Administration has initiated a program named the Process Analytical Technology (PAT) in order to ensure efficient quality monitoring at each stage of the manufacturing process by the integration of analytical systems into the procedure. Improving consistency and predictability of tablet action by improving quality and uniformity of tablets is required. An ideal technique for quality monitoring would be non-invasive, non-destructive, rapid, intrinsically safe and cost-effective. The objective of the current investigation was to develop, non-contact/non-destructive techniques for monitoring and evaluating drug tablets for mechanical defects such as coating layer irregularities, internal cracks and delamination using a laser-acoustic approach. In the proposed system, a pulsed laser is utilized to generate non-contact mechanical excitations and interferometric detection of transient vibrations of the drug tablets. Three novel methods to excite vibration in drug tablets are developed and employed: (i) a vibration plate excited by a pulsed-laser, (ii) pulsed laser-induced plasma expansion, and (iii) an air-coupled acoustic transducer. Nanometer-scale transient surface displacements of the drug tablets are measured using the laser interferometer. Signal processing techniques are then applied to these transient displacement responses to differentiate the defective tablets from the nominal ones. From the analysis of frequency spectra and the time-frequency spectrograms obtained under both mechanisms, it can be concluded that defective tablets can be effectively differentiated from the nominal ones.