Sentronic and mk teknology1 are partner to the pharmaceutical industry in India focussing on NIR based PAT solutions for solid dose manufacturing processes.With a strong focus to applications in diffuse reflectance, the typical unit operations in batch and continuous processing can be monitored in real time. Based on the powerful SentroPAT system series, Sentronic offers solutions to realize PAT in all phases, from early process and product development, process transfer to routine operation and also process troubleshooting. All Sentronic systems comply with pharmaceutical industry requirements and regulations and the systems and software are developed according to GAMP. Comprehensive documentation and validation packages as well as services for GMP qualification are completing the portfolio Sentronic is offering to customers in the pharmaceutical industry.
Continuous Manufacturing (CM) offers many attractive properties for the pharmaceutical manufacturing industry such as enhanced consistency of production as well as the ability to dial up a design space point for experimental formulation or process design or to scale output of manufacture seemlessly. As solid oral dosage form CM becomes more common place in the pharmaceutical industry, PAT deployment in these processes has become an essential part of the control strategy and the basis of Real Time Release Testing (RTRT). As such, the speed and robustness of the PAT measurements are of paramount importance. Other considerations in ensuring the quality & robustness of in-line PAT measurements in a CM environment such as robustness of the measurement, stability of the instrument and consistency between instruments to facilitate calibration transfer. Sentronic offers unparalleled high performance in these areas. In addition, Sentronics fully validated SentroSuite software platform offers excellent compliance in data integrity and 21CFR11. Sentronic Analysers can be directly integrated into the PAT stack with Siemens SiPAT, Optimal SynTQ and Perceptive Engineering PharmMV for process control integration.
Direct compression after blending and lubrication has been the mainstay of Solid Oral Dosage Form pharmaceutical manufacturing for over 100 years. Until now the only way to verify content uniformity and assay in the tablet has to been to take a very small sample and perform laboratory testing for quality control purposes. This is an expensive, slow and laborious process that results in a large amount of very high value material being held in inventory awaiting QC release for final processing steps. Well known issues such as blend segregation that cause sub or super potent material to be produced during the tabletting run can be very difficult to detect and assess using these traditional QC tools. At-line PAT solutions have proven to be expensive and difficult to implement. Recent advances in inline PAT measurement systems such as the miniaturisation of measurement technology in the Sentronic DRLS measurement head has meant that is now possible to continuously monitoring tablet die filling blend potency and uniformity through out the entire tabletting production run. This is a cost effective way to ensure production consistency and quality and significant enabler of Real Time Release Testing.
This typical pharmaceutical production process is a fast process, which is known for producing very dense granules resulting in a slow release of the API in the body. The process consists of three phases a) dry mixing, b) liquid addition and c) massing or granulation.Why use NIR technology to monitor HSWG?
NIR spectroscopy is the only analyzer technology which provides deep insight about the physical and chemical properties during the process at very high measurement speed. It can detect changes in the particle size of excipients or API during the mixing phase and detect the end point based on the homogeneity in this phase, variation in particle growth throughout the process. Free and bound moisture can be monitored, since they have different effects on the NIR spectra. The monitoring of the dissolution of sugars during the granulation could be followed as well.Why Diode array technology
Diode array spectrometers are much faster than other available technologies. In our optimized SentroPAT diode array systems a typical integration time is only approx. 10 ms giving an overall measurement interval of 1 sec or less. But even further, a diode array NIR detects all wavelengths of the spectrum simultaneously. This is totally different to all other NIR technologies including FT-NIR. When sample presentation is not constant during the process, (typical in the case of smaller granulators,) every single spectrum looks smooth. Only the baseline might be at different heights. Fast variations in a scanning spectrometer would make the spectrum unusable or show only noise. Similar effects reduce the data quality in FT-NIR systems.
The blending of pharmaceutical ingredients is one of the critical processes during the production of pharmaceuticals. Product homogeneity and further processing is dependant on the characteristics of the incoming material and process conditions. Sample taking and analysis at the end of the process is most commonly used for quality control, however this does not provide any information to enable optimisation of the process and doesn't provide any process information.
Applying online NIR using SENTROPAT BU model to this process allows the determination of the blending end point by statistical methods. Beside this option the quantitative analysis of API or functional ingredients by applying a chemometric calibration is possible too.Based on the gained process data it is possible to optimize blending time, avoid faulty batches and prevent blend from being separated due to over-blending.
There is no longer need for conventional thief sampling and laboratory analysis which retard manufacturing processes and therewith raise production costs. This makes a PAT solution to a very valueable tool in process and formulation development, up-scaling, and routine use. Fully implemented and applied the online monitoring of blend uniformity is a key element for real-time release.