Receiver operating characteristic analysis for the selection of threshold values for detection of capping in powder compression

doi:10.1016/j.ultras.2004.02.015

Ultrasonics

Volume 42, Issues 1–9, April 2004, Pages 149-153

https://doi.org/10.1016/j.ultras.2004.02.015 Get rights and content

Abstract

The acoustic emission (AE) energy obtained from compressing lactose powder to form pharmaceutical tablets was chosen for condition monitoring of the tablets. The method used was based on the setting of an AE energy decision threshold such that problems of tablet capping and lamination were successfully identified. Capping and lamination are the most common types of problem that can occur in tablets manufacturing using a powder compression process. To assess the performance of a classifier, use was made of a receiver operating characteristic curve (ROC) obtained by plotting the correct detection probability against the false alarm probability based on AE energy distributions for capped and non-capped tablets. The area under the ROC curve, referred to as the AUC, determines the level of competency of the classifier. A value of 0.5 suggests a mere hazarding of guesses whilst a value of 1 indicates correct classification every time. The AE energy approach for tablet capping monitoring gives an AUC value of 0.96, thereby suggesting the possibility of a highly accurate classifier. With the assumption that penalties for false alarm and missed detection are equally severe, using the graphical method of expected penalty cost (EPC), the optimal AE energy decision threshold was established to be 1.2 × 10⁸ units, at which the maximum correct capping detection rate of 95% was achieved. The paper also explains how a decision threshold can be obtained when the two penalties are not equal.

Introduction

Early detection and accurate diagnosis of incipient faults can prevent process failure and consequently improve reliability and safety of the process, and reduce its downtime and the overall operating cost. Continuous on-line condition monitoring with fault diagnosis is therefore an important strategy in the manufacturing of pharmaceutical products. It affords an effective means for determining whether the process is operating to specification and if it is not, to identify the nature of the faults.

Capping and lamination are common problems in pharmaceutical tablets manufacturing by means of compressing powder into a compact [1]. Capping generally refers to the lid of a biconvex tablet being separated from the compact. Capping may occur at one end of a compact or both. Lamination involves the occurrence of layers in a compact parallel to the punch face. Since lamination is a precursor to capping, the terms lamination and capping are often used interchangeably.

Section snippets

Acoustic emission for condition monitoring

Acoustic emission (AE) is a release of transient strain energy due to abrupt changes in stress within a material [2]. The energy release results in a mechanical wave that propagates within, and on the surface of, a structure. The term AE can also be used to denote any technique that is based on the phenomenon just described. AE has been used for condition monitoring [3] and material evaluation [4]. This paper presents the application of AE for the condition monitoring of the tablet formation

Method and technique

The material examined in the present study was an 80/20 lactose/povidone mixture. It was compressed on a single-tablet Manesty-F3 press at a rate of 50 tablets per minute. Fig. 1 shows a schematic diagram of the experimental setup. The lower punch was used to control the depth of the cavity and hence the thickness of the compact produced whilst the upper punch was driven to provide the necessary compression. Both punches had a radius of 5 mm and a concave surface with a maximum depth at its

Results and discussion

Fig. 2 shows a typical result of the AE energy values for 20 consecutive compression cycles of tablet-formation. Capping is characterised by the low AE energy compared to non-capped tablets. The unit for the AE energy in Fig. 2 is a MISTRAS defined unit that is proportional to the voltage squared of the AE signal.

Conclusion

Condition monitoring of tablet production using AE energy has been shown to be an effective method. The method could discriminate between capped (faulty) and non-capped (good) tablets based on comparing the measured level of AE energy against a decision threshold. This threshold was set in such a way that the classifier would minimise the total penalty cost of raising a false alarm and of missing a fault. In this method it is not necessary to know the individual penalty costs for these two

Acknowledgements

The authors wish to acknowledge the support of EPSRC (Grant GR/M44200) and the nine industrial collaborators including GlaxoSmithKline and Unilever Research within the INTErSECT Faraday Partnership Flagship Research Project (1998–2002) entitled “Acoustic Emission Traceable Sensing and Signature Diagnostics (AESAD)”. Particular thanks are due to Dr. D Rudd, Dr. P Frake and Dr. P Doyle.

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There are several unpredictable problems such as capping, lamination, binding, or sticking that can occur during the commercial scale tableting process. Many researchers have studied and evaluated these phenomena.1-5 In particular, these phenomena are most commonly experienced at the time of scale-up from the laboratory to a pilot or commercial scale.
Sticking is a common observation in the scale-up stage on the punch tip using a commercial tableting machine. The difference in the total compression time between a laboratory tableting machine and a commercial one is considered one of the main root causes of scale-up issues in the tableting processes. The proposed “Size Adjusted for Scale-up punch” can be used to adjust the consolidation and dwell times for commercial tableting machine. As a result, the sticking phenomenon is able to be replicated at the pilot scale stage. As reported in this article, the quantification of sticking was done using a 3-D laser scanning microscope to check the tablet surface. It was shown that the sticking area decreased with the addition of magnesium stearate in the formulation, but the sticking depth was not affected by the additional amount of magnesium stearate. It is proposed that the use of a 3-D laser scanning microscope can be applied to evaluate sticking as a process analytical technology tool, and so sticking can be monitored continuously without stopping the machine.
Structure analysis and denoising using Singular Spectrum Analysis: Application to acoustic emission signals from nuclear safety experiments
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It is used to detect and/or monitor defaults and cracks in materials (e.g. [1]), and to monitor the compaction of various powders (e.g. [2–4]), including nuclear fuel powders [5,6]. Some works also focus on the correlation between acoustic signatures and physical mechanisms during tests (e.g. deformation, fragmentation, rupture…) (e.g. [7,6]). This methodology is of interest for characterizing the structure health in RIA conditions.
We explore the abilities of the Singular Spectrum Analysis (SSA) to characterize and denoise discrete acoustic emission signals. The method is first tested on simulated data for which different types and levels of noise are considered. It is then applied on real data recorded from nuclear safety experiments. The results show an excellent ability of the SSA to characterize the corrupted signal and to detect structural changes, even for low signal-to-noise ratio. For denoising purposes, the quality of the results depends mainly on the separability between the source signal to be estimated and the noise. However, whatever the case, the main components of the source signal are clearly identified when the components associated with the noise are removed.
Identification of the fragmentation of brittle particles during compaction process by the acoustic emission technique
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Indeed, the final step of the process (i.e. the ejection of the compact) may create defaults inside the compact that can be detected through the comparison of the number of the acoustic events and AE energy rate between the undamaged compacts and the damaged counterparts. Some works also focus on the correlation between mechanisms during compaction (e.g. deformation, fragmentation, friction, etc.) and acoustic signatures [25]. Nevertheless they usually consider continuous signals and the evolution of the number of counts, rarely the discrete signals and the evolution of parameters such as amplitude, waveform, rise time, time duration, and frequency.
Some nuclear fuels are currently manufactured by a powder metallurgy process that consists of three main steps, namely preparation of the powders, powder compaction, and sintering of the compact. An optimum between size, shape and cohesion of the particles of the nuclear fuels must be sought in order to obtain a compact with a sufficient mechanical strength, and to facilitate the release of helium and fission gases during irradiation through pores connected to the outside of the pellet after sintering. Being simple to adapt to nuclear-oriented purposes, the Acoustic Emission (AE) technique is used to control the microstructure of the compact by monitoring the compaction of brittle Uranium Dioxide (UO₂) particles of a few hundred micrometers. The objective is to identify in situ the mechanisms that occur during the UO₂ compaction, and more specifically the particle fragmentation that is linked to the open porosity of the nuclear matter. Three zones of acoustic activity, strongly related to the applied stress, can be clearly defined from analysis of the continuous signals recorded during the compaction process. They correspond to particle rearrangement and/or fragmentation. The end of the noteworthy fragmentation process is clearly defined as the end of the significant process that increases the compactness of the material. Despite the fact that the wave propagation strongly evolves during the compaction process, the acoustic signature of the fragmentation of a single UO₂ particle and a bed of UO₂ particles under compaction is well identified. The waveform, with a short rise time and an exponential-like decay of the signal envelope, is the most reliable descriptor. The impact of the particle size and cohesion on the AE activity, and then on the fragmentation domain, is analyzed through the discrete AE signals. The maximum amplitude of the burst signals, as well as the mean stress corresponding to the end of the recorded AE, increase with increasing mean diameter of the particles. Moreover, the maximum burst amplitude increases with increasing particle cohesion.
Methods for the practical determination of the mechanical strength of tablets - From empiricism to science
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One advantage of this method is that the position and orientation of these defects can be determined. This method was used successfully, for example, for the prediction of capping and lamination of tablets (Au et al., 2004). It has also been shown that it is possible to predict delamination tendencies in multi-layer tablets with this technique (Akseli et al., 2009a), because the method allows the characterisation of the defect state of the individual layers and the interface, plus it is sensitive to anisotropic behaviour of the layers due to inhomogeneous relaxation processes.
This review aims to awake an interest in the determination of the tensile strength of tablets of various shapes using a variety of direct and indirect test methods. The United States Pharmacopoeia monograph 1217 (USP35/NF30, 2011) has provided a very good approach to the experimental determination of and standards for the mechanical strength of tablets. Building on this monograph, it is hoped that the detailed account of the various methods provided in this review will encourage industrial and academic scientists involved in the development and manufacture of tablet formulations to take a step forward and determine the tensile strength of tablets, even if these are not simply flat disc-shaped or rectangular. To date there are a considerable number of valid test configurations and stress equations available, catering for many of the various shapes of tablets on the market. The determination of the tensile strength of tablets should hence replace the sole determination of a breaking force, because tensile strength values are more comparable and suggestions for minimum and/or maximum values are available. The review also identifies the gaps that require urgent filling. There is also a need for further analysis using, for example, Finite Element Method, to provide correct stress solutions for tablets of differing shapes, but this also requires practical experiments to find the best loading conditions, and theoretical stress solutions should be verified with practical experiments.
In-line ultrasound measurement system for detecting tablet integrity
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As capping and lamination change the mechanical properties of the tablet, acoustic measurement systems, which are sensitive to mechanical changes, have been studied extensively. One of the first monitoring systems for defect tablet detection was a measurement system based on acoustic emission (AE) (Waring et al., 1987; Serris et al., 2002; Joe Au et al., 2004). Mechanisms of deformation generate AE signals that can be detected, and these acoustic responses may give information on the compression process during tablet formation.
An ultrasound measurement system for tablet defect detection is introduced. The measurement system was implemented in an eccentric single station tabletting apparatus, where ultrasound transducers were placed inside the upper and lower punches. These instrumented punches were then used to measure the speed of sound and ultrasound attenuation values in both intact and defective tablets made from dibasic calcium phosphate, microcrystalline cellulose and lactose monohydrate. Ultrasound attenuation was found to be a very sensitive method to discriminate defective tablets from intact ones. In addition, it was found that the determined ultrasound attenuation was different between all three materials used in this study, which indicates that different materials could be distinguished from one another by this detection method.
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Receiver operating characteristic analysis for the selection of threshold values for detection of capping in powder compression

Abstract

Introduction

Section snippets

Acoustic emission for condition monitoring

Method and technique

Results and discussion

Conclusion

Acknowledgements

Semin. Nucl. Med.

Studies of Variables that effect Tablet Capping

Pharm. Tech.

Introduction to acoustic emission

Material Evaluation