Ilgaz Akseli

Mechanical Property Characterization of Bilayered Tablets using Nondestructive Air-Coupled Acoustics

A noncontact/nondestructive air-coupled acoustic technique to be potentially used in mechanical property determination of bilayer tablets is presented. In the reported experiments, a bilayer tablet is vibrated via an acoustic field of an air-coupled transducer in a frequency range sufficiently high to excite several vibrational modes (harmonics) of the tablet. The tablet vibrational transient responses at a number of measurement points on the tablet are acquired by a laser vibrometer in a noncontact manner. An iterative computational procedure based on the finite element method is utilized to extract the Young’s modulus, the Poisson’s ratio, and the mass density values of each layer material of a bilayer tablet from a subset of the measured resonance frequencies. For verification purposes, a contact ultrasonic technique based on the time-of-flight data of the longitudinal (pressure) and transverse (shear) acoustic waves in each layer of a bilayer tablet is also utilized. The extracted mechanical properties from the air-coupled acoustic data agree well with those determined from the contact ultrasonic measurements. The mechanical properties of solid oral dosage forms have been shown to impact its mechanical integrity, disintegration profile and the release rate of the drug in the digestive tract, thus potentially affecting its therapeutic response. The presented nondestructive technique provides greater insight into the mechanical properties of the bilayer tablets and has the potential to identify quality and performance problems related to the mechanical properties of the bilayer tablets early on the production process and, consequently, reduce associated cost and material waste.

Non-destructive determination of anisotropic mechanical properties of pharmaceutical solid dosage forms.

The mechanical property anisotropy of compacts made from four commercially available pharmaceutical excipient powders (microcrystalline cellulose, lactose monohydrate, ascorbic acid, and aspartame) was evaluated. The speed of pressure (longitudinal) waves in the uni-axially compressed cubic compacts of each excipient in the three principle directions was determined using a contact ultrasonic method. Average Youngs moduli of each compact in the axial (x) and radial (y and z) directions were characterized. The contact ultrasonic measurements revealed that average Youngs modulus values vary with different testing orientations which indicate Youngs modulus anisotropy in the compacts. The extent of Youngs modulus anisotropy was quantified by using a dimensionless ratio and was found to be significantly different for each material (microcrystalline cellulose>lactose>aspartame>ascorbic acid). It is also observed that using the presented contact method, compacts at high solid fraction (0.857-0.859) could be differentiated than those at the solid fraction of 0.85 in their groups. The presented contact ultrasonic method is an attractive tool since it has the advantages of being sensitive to solid fraction ratio, non-destructive, requiring small amount of material and rapid. It is noteworthy that, since the approach provides insight into the performance of common pharmaceutical materials and fosters increased process knowledge, it can be applied to broaden the understanding of the effect of the mechanical properties on the performance (e.g., disintegration profiles) of solid oral dosage forms.

Non-destructive acoustic defect detection in drug tablets.

For physical defect detection in drug tablets, a non-destructive and non-contact technique based on air coupled excitation and interferometric detection is presented. Physical properties and mechanical integrity of drug tablets can often affect their therapeutic and structural functions. The monitoring for defects and the characterization of tablet mechanical properties therefore have been of practical interest for solid oral dosage forms. The presented monitoring approach is based on the analysis of the transient vibrational responses of an acoustically excited tablet in both in temporal and spectral domains. The pulsed acoustic field exciting the tablet is generated by an air-coupled transducer. Using a laser vibrometer, the out-of-plane vibrational transient response of the tablet is detected and acquired in a non-contact manner. The physical state of the tablet is evaluated based on the spectral properties of these transient responses. In the current study, the effectiveness of three types of simple similarity measures is evaluated for their potential uses as defect detection norms, and for their potential use in quantifying the extent of tablet defect is discussed. It is found that these quantities can not only be used for identification of defective tablets, but could also provide a measure for the extent of the damage.

Ultrasonic determination of Young's moduli of the coat and core materials of a drug tablet

Many modern tablet presses have system controls that monitor the force exerted to compress the solid oral dosage forms; however this data provides only limited information about the mechanical state of the tablet due to various process and materials uncertainties. A contact pulse/echo ultrasonic scheme is presented for the determination of the local Youngs moduli of the coat and the core materials of enteric-coated and monolayer coated tablets. The Youngs modulus of a material compacted into solid dosage can be related to its mechanical hardness and, consequently, its dissolution rate. In the current approach, short ultrasonic pulses are generated by the active element of a delay line transducer and are launched into the tablet. The waveforms reflected from the tablet coat-core interface are captured by the same transducer and are processed for determining the reflection and transmission coefficients of the interface from partially overlapping echoes. The Youngs moduli of the coat and the core materials are then extracted from these coefficients. The results are compared to those obtained by an air-coupled acoustic excitation study, and good agreement is found. The described measurement technique provides greater insight into the local physical properties of the solid oral dosage form and, as a result, has the potential to provide better hardness-related performance predictability of compacts.

Air-coupled non-contact mechanical property determination of drug tablets.

A non-contact/non-destructive technique for determining the mechanical properties of coated drug tablets is presented. In the current measurement approach, air-coupled excitation and laser interferometric detection are utilized and their effectiveness in characterizing the mechanical properties of a drug tablet by examining its vibrational resonance frequencies is demonstrated. The drug tablet is vibrated via an acoustic field of an air-coupled transducer in a frequency range sufficiently high to excite its several vibrational modes (harmonics). The tablet surface vibrational responses at measurement points are acquired by a laser vibrometer in a non-contact manner. An iterative computational procedure based on the finite element method is developed to extract the mechanical properties of the coated tablet from a subset of its measured resonance frequencies. The mechanical properties measured by this technique are compared to those obtained by a standard contact ultrasonic measurement method and a good agreement is found. Sensitivities of the resonance frequencies to the changes in the tablet mechanical properties are also obtained and discussed. The presented non-destructive technique requires no physical contact with the tablet and operates in the microsecond time-scale. Therefore, it could be employed for rapid monitoring and characterization applications.

Real-time Acoustic Elastic Property Monitoring of Compacts During Compaction

A nondestructive, real-time acoustic technique for determining elastic properties of compacts during compaction is presented. An acoustic time-of-flight study was conducted, and the extraction of the linear elastic properties of calcium carbonate compacts was demonstrated. To verify the results of the acoustic experiments, a uniaxial compaction investigation was also carried out using a computer-controlled press with an instrumented die. Good agreement between linear elastic properties determined using both acoustic experiments and compaction force-displacement data was observed. This technique has the potential to be used as a real-time compaction monitoring tool.

Non-Contact Rolling Bond Stiffness Characterization of Polyvinylpyrrolidone (PVP) Particles

Two techniques, based on a contact lateral pushing and a noncontact base excitation, were utilized to characterize the adhesion behavior of polyvinylpyrrolidone (PVP) particles. The micro-spherical PVP particles deposited on silicon substrates were excited by an ultrasonic transducer and the transient particle response was acquired by an interferometer. The natural frequencies of the particle rocking motion were extracted by comparing the vibrational spectra of the particles to those of the substrate. The obtained frequencies were then used to determine the work of adhesion of the contact. Rolling resistance moment-based lateral pushing experiments were also conducted on similar PVP particles. The resulting slopes of force–displacement curves were utilized to obtain the work of adhesion. The work of adhesion results determined from the noncontact measurements and lateral pushing measurements were in good agreement. In order to characterize the particle/substrate adhesion bond, different contact modes (i.e., rigid contact, neck-shaped contact, and an equivalent torsional spring) in the contact area were considered. For each case, the expected natural frequencies of the rocking motion were extracted from the slopes of force–displacement curves obtained in the contact lateral pushing experiments. The existence of all possible modes of the particle/substrate bond was verified because all expected natural frequencies were observed in the noncontact acoustic measurements.

Acoustic Testing and Characterization Techniques for Pharmaceutical Solid Dosage Forms

The mechanical state of a drug tablet is an important factor in its physical form and therapeutic function. In recent years, a strong need for new technologies for faster and more reliable quality assurance has often been voiced by both regulators and manufacturers. In the current study, a novel air-coupled acoustic technique is demonstrated as a noncontact/nondestructive method for mechanical characterization and coating thickness determination of tablets. For verification purposes, a contact ultrasonic scheme is employed. Applications of the technique in solid dosage form characterization and process monitoring applications and its role as a potential PAT tool are discussed.

Multimode Air-Coupled Excitation of Micromechanical Structures

The development of an acoustic measurement system for multimode air-coupled excitation and detection of micrometer-scale cantilever structures, which are, for example, used in micro-electromechanical systems (MEMSs), is detailed and reported for the first time. The source of noncontact vibrational excitation is a pulsed acoustic field generated by an air-coupled transducer. In the experimental system, the transient response of the cantilever beam is obtained at various points along the beam axis to extract its resonance frequencies and corresponding mode shapes. We demonstrate that measurable amplitudes of vibrations can be obtained at various excitation levels in the megahertz range, and higher harmonics of vibration of a microbeam can be excited by the air-coupled mechanism from a distance on the order of 10 mm. In the specific utilizations of the reported system, resonance frequencies and mode shapes can be related to the mechanical properties and geometric attributes (dimensions and defects), as well as the residual stress state in a microstructural element using various established computational and experimental inverse techniques. Another potential application area of the reported system is in the sensors for detecting the bending stiffness of deposited films on cantilever oscillators (in addition to its film mass loading) to increase the detection sensitivity and selectivity in a single sensing element.