Cover Story - Planning Ahead
Although the general process of solid dosage tablet compression has not significantly changed in more than 100 years, advances in tablet manufacture and quality continue to be made by forward-thinking companies in the industry. Tablet presses are becoming faster, more efficient, and more automated. Gone are the days when tablets could only be tested following a batch run. Tablet properties can now be monitored throughout the compression cycle to ensure conformity and quality. Automated testing and analysis can now be run during tablet manufacture to improve quality by identifying if problems such as inconsistent weight or dimensional non-uniformity arise during a batch. Using new available technology to monitor tablet production allows manufacturers to address such issues immediately, rather than waiting for testing and/or wasting product and technicians’ time. Batch records captured using new technology can also assist in process improvement and support the release of lots.
The pharmaceutical industry is going to continue to look for ways to produce tablets more efficiently and at a level of quality that meets consumers’ expectations. Natoli Engineering Company, Inc. has partnered with leading solid dosage technology providers to provide innovative solutions the industry needs to ensure quality tablets. Natoli will debut their new tablet press, the NP-400, which has been designed to enable Process Analytical Technology (PAT) solutions, at the ACHEMA exhibition in Germany, June 15-19, 2015.
Powder Components are Integral to Tablet Quality
The physical properties of a tablet are determined when the drug product formulation encounters the compression tools in the tablet press. The correct active pharmaceutical ingredient dose is brought to this point by a properly prepared recipe of powder components which have been appropriately granulated and/or blended. This formulation is delivered as a stable homogeneous mixture to be placed on to the die table of the press via a gravity or power feeder.
The compression of that proper dose will determine the physical properties of the tablet and thus determine proper delivery of the medicine to the patient through specified tablet disintegration and dissolution performance. These physical qualities are arguably the most important to a product’s success. Warnings, recalls and loss of consumer trust can result from inadequate tablet analysis and failure to deliver proper dose in the tablet.
Most modern tablet presses offer automation systems that provide system control and data acquisition during the manufacture of tablets. These systems are used to ensure conformity of the physical properties of tablets to their specified parameters. Some pharmaceutical manufacturers have found a need to use more advanced methods to ensure their tablets adhere to such standards.
The use of process analytical technology (PAT) to monitor the critical process parameters of oral solid dosage processes has been adopted by some of these manufacturers to understand and control the processes involved in formulation preparation and tablet compression. Near infrared spectroscopy (NIR) has been utilized as a method to monitor product formulation blend uniformity as it comes on to the tablet press either at the exit of the powder chute or in the feed frame. NIR has also been utilized to monitor tablet properties immediately after compression. Either measurement location is capable of recognizing tablet content uniformity or physical property anomalies so that suspect tablets can be rejected and the integrity of the rest of the manufacturing lot retained.
Testing and rejecting nonconforming tablets immediately after compression can present significant advantages to manufacturers employing the technology. In addition to producing consistently higher quality tablets, they also can improve efficiency and reduce costs by identifying nonconforming tablets during production. The opportunity to correct issues during lot manufacture saves time and prevents formulation waste.
Presses and Product Advances
International tooling manufacturer Natoli Engineering Company is working with instrument manufacturers to add this technology to Natoli’s tablet press offerings. Natoli recently introduced a new tablet press, the NP-400, which was designed with many attributes that will make it stand out from other presses of its class currently on the market. The NP-400 is a medium output workhorse capable of running around the clock, producing up to 180,000 tablets per hour. The NP-400 utilizes a supervisory control and data acquisition system (SCADA) to continuously monitor the tablet precompression and main compression forces, the tablet ejection force, tablet take off force, press temperature and humidity as well as the lubrication and utilities of the press operation. Its single footprint, off-shelf-controls, and self-lubricated turret provide an efficient and simple operational setup.
In the way that features such as auto-lubrication have become indispensible on tablet presses, spectroscopy is set to become an important option for tablet analysis during manufacture. Natoli has worked in cooperation with its instrumentation partners to integrate an NIR system onto its newest press. A design to implement a NIR probe to examine tablets post compression, on the die tablet, has been designed into the frame of the tablet press.
Such a probe can take the NIR spectrum of each tablet after compression and utilizes a multivariate calibration model to determine whether the tablet is within the specification range. In the event that tablets are out of specification, the NIR controller will communicate with the NP-400’s on-machine SCADA system and the tablets will be directed to the reject chute of the tablet press for later evaluation. This capability will enable customers to generate a data rich batch record that can be used for lot release support and process improvement options for the drug product manufacturing process.
Natoli Engineering will also demonstrate an additional tablet testing and analysis system at the ACHEMA exhibition. The Kraemer Tablet Testing System complements the monitoring and control systems provided by the NP-400 data acquisition system and can be integrated with an on board NIR to assess content uniformity.
This system can be used to test sample tablets taken from the tablet press at predetermined intervals so that the manufacturing batch can be characterized from the beginning to the end. The system tests the tablets for weight, thickness, diameter, hardness and content uniformity. Content uniformity is determined by utilizing an integrated NIR system. A combination of the real time tablet press monitoring systems with the offline tablet testing data delivers a comprehensive assessment of tablet compression performance. The data package provided could be a significant chapter in a real time release testing protocol that will offer Natoli’s customers the opportunity to realize significant cost savings through reduced laboratory testing and faster lot release of the tablets to the packaging department and on to the patient.
Partnerships Provide Solutions
The future of innovation in tablet manufacturing will require cooperation and partnerships among vendors in order to continue to advance solid oral dosage manufacturing practices for batch manufacturing as well as in the up and coming world of continuous manufacturing. The implementation of on-line and at-line PAT techniques will require a complimentary dossier of research and development work that validates the measurement and control techniques in order to achieve the utility and value of the installed analyzers and control system. Natoli is positioning their tablet press offerings to allow the smaller scale pharmaceutical company or contract manufacturer to implement and realize the economic value of this approach to modernization. These solutions provide economical opportunities to companies looking to improve tablet quality and improve manufacturing efficiency.