Powder Characterisation System - PTG-NIR PTG-NIR Powder Characterisation System (not yet released for selling to end users) The PTG-NIR automatic powder and granule inspection system with integrated NIR spectrometer may be used to examine the flow characteristics of a powder or granule. The combination of a Powder Testing System with a NIR Diode Array spectrometer shall be used for simultaneous detection of chemical, physical and morphological information. This information is describing the flow behaviours of a powder or granule. Other forms of solids are possible to be tested too. All the parameters are shown as one result: The flow property. The automated PTG S3 stand-alone powder testing system is used to measure the flow behaviour of granules and powders in compliance with the EP <2.9.36> and USP <1174> pharmacopoeia and ISO 4324 standards. It has a self contained balance and a built in printer for a compact foot print. The all stainless finish (for GMP compliance), is easy to clean and maintain. 41-03200_09.1.0E Page 1 of 5
Powder Characterisation System - PTG-NIR The NIR Diode Array spectrometer is built-into a separate stainless steel box from which the fibre optic cable is directly connected to the PTG S3 instrument. This combination is the PTG-NIR. The NIR measurement accessory will greatly enhance the application range of this instrument. Greatly expanded application range The PTG-NIR will be equipped with an addition NIR Diode Array spectrometer, from which the fibre probe neatly fits into the powder flow nozzle holder for the additional analysis of: Qualitative finger printing of powder content Moisture content API concentration Homogeneity of blended components This important step forward means that the range of analytical information available from a single powder sample has now been greatly increased. In Pharmaceutical applications, we can now analyse all incoming raw materials (e.g., nonactive ingredients) for their official content as well as the water content. Blends of the non-active materials can also now be analysed for flow characteristics as well as important features such as water content which will affect the way that the powder mix will flow into the tabletting machine for example. The example below shows the ability of the system to shed light on the increased concentration of sugar in the excipient blend. It can also shed light on the distribution of an API within a powder blend. This can now be extended to give indications for content uniformity. Powder Characterisation is Critical Absorbance [AU] 4 3 2 1 0 78,2% Zucker 80,4% Zucker 81,8% Zucker 85,7% Zucker 90% Zucker 100% Zucker Analysis of Blended Components. Note the clearly indicated increase in sucrose concentration shown by the PTGS NIR Analyser -1-2 1100 1200 1300 1400 1500 1600 1700 1800 1900 2000 2100 Wellenlänge [nm] 41-03200_09.1.0E Page 2 of 5
Applications for this system are: Determination of these properties in the goods inspection Determining the required properties prior to the processing of intermediate products, especially considering (e.g. capsule filling) or injection (e.g. Tablet Press) The study of segregation operations The PTG-NIR is a robust laboratory analysis system. In this case is the NIR spectrometer with a fibre optic cable connected with the PTG S3. Functioning of the Set-Up: The material is inside a conical hopper within the PTG S3 Powder testing System. The powder is poured through a flow nozzle, the size is selected according to the particle size and flow capacity of the test material. After opening the funnel cap the powder is captured on a table and forms a conical pile. These tests can be selected by the user: Flow time, the Bulk Cone (cone angle or angle of repose), the Cone Volume, Weight and Density and the Weight Increase. All data are registered and documented. Additionally the powder flow stream which passes the measuring optics which is connected via a fibre cable with the spectrometer will be analysed. The beam penetrates only about 1/10 to 3/10 mm into the product stream and is reflected by its particles. The optical analysis is done without product contact, contamination-free and non-destructive. The quantity of tested material is generally 100 to 350 ml. The resulting flow time is usually only a couple of seconds. In order to receive as much information as possible, it is necessary that the spectral range in size, resolution and a sufficient number of spectra is recorded for a profile which is representative. Typical is the set-up are about 50 spectra for the flow time experiment. Those requirements can only be offered using a Diode Array Spectrometer based technology. Other techniques such as FT-NIR, AOTF or others, are not suitable due to the speed requirement to collect full spectra. What is fundamentally necessary to use of the system? NIR calibration data with corresponding reference methods are necessary because the NIR reflectance spectroscopy is a method, which only relative sizes can spawn. Thus, it is recommended, to calibrate the moisture content with LOD or Karl Fischer titration. Other concentrations have to be calibrated by orthogonal reference methods. This effort initially seems great, but usually it is known for quantitative analysis in the lab. The analysis and evaluation of the spectra is done using chemometrical procedures. Simple linear models to complex nonlinear models are possible. Software: The system software should be very easy to operate and has 4 different user levels. In the "operator" mode, only analysis with preset measurement and evaluation parameters is possible. After the analysis a full report is filed and may be printed. This type of instrumentation is easily used to provide: Reduction in cost of raw process materials: reject bad batches before processing Maintenance of the optimum formulation for the process concerned Reduction in process costs Maintain the quality and consistency of the final product 41-03200_09.1.0E Page 3 of 5
Maintain process efficiency and costs by optimisation of product storage, packing, handling and transportation. Maintain powder quality from different suppliers or from the same supplier over a long time period; use the finger print facility of the PTGS3 NIR for rapid QC checks. Development of new processes where powders are required to be formulated into end products. Check moisture effects: use of powders in open systems in different climates; use the NIR option for water content control. Investigating and maintaining the quality of dry mixes What else can the PTG-NIR do for me? The PTG-NIR can also be used to great effect in order to: Improve product consistency from batch to batch Keep tight control of component powders, especially if they are natural products Compare sources of powdered products: both excipients and APIs. Easy method to achieve quality control on bulk incoming component products Easy method for the control of dry and wet mixing, tabletting, granulating, and capsule filling Prediction of powder transport through conveyors, air lifts and in silos Prediction of powder suitability for capsule and bottle filling Prediction of product settling during transport, so called classification Prediction of powdered mix influence on tablet hardness and solid dosage form stability Prediction of powder influence on tablet disintegration and friability The physical parameters measured by the PTG-NIR: Powder Flow Time of a pre defined mass Powder cone volume Powder cone density Cone Angle (Angle of Repose EP <2.9.36>, USP <1174>) Flowability of 100 mg of product (EP/DAB <2.9.36>, USP <1174> pharmacopoeia) Amount of sample (mg in a preset time) Flow Chart of sample (mg/time) Technical Details of the PTG Powder Tester Display: LCD Display Keyboard: alpha-numerical and function keys Key entries: 12 digit product code 12 digit batch number Volume of the st. steel cone: approx. 450 ml Range for cone angle*: 1.0 to 45.0 Range for "flowability" test*: 0.1 sec. to 999 sec. - mass: 100 g Range for flow time test*: 0.1 sec. to 999 sec. Cone density*: 0.000 g/ml -1 to 6.0 g/ml -1 Cone weight*: 1 mg to 325 g Cone volume*: 0.1 ml to 275 ml Interface: RS-232 serial interface 41-03200_09.1.0E Page 4 of 5
Printer: Instrument housing: Included documentation: built-in Thermo Printer and/or external Parallel printer port stainless steel to meet GLP requirements GLP compliant IQ/OQ Documentation * theoretically maximum measurable data by the built-in electronics Technical Data for the NIR Analyser Wavelength range: Wavelength Accuracy: Wavelength reproducibility: Pixel distance: Noise : Baseline stability: Scan speed: 1100 2100nm < 1nm (at 1261.8nm, 1681.4nm & 1935.5nm) < 0. 1 nm 3.9 nm Max.< 0.8mAU. Mean <0.3mAU < 3 mau / hour (at 1400 nm and 1700 nm) 20 Spectra / sec Detection system (Mono-fibre) Connector Type (Spectrometer): FSMA 905 Connector Type (PTGS3): 3 mm Fibre Diameter: 600μm Numerical Aperture: 0.22 Illumination Fibre (bundle) Light source Connection: FSMA 905 PTGS3 Connection: 3mm Light Fibre diameter: 6 x 600μm Numerical Aperture: 0.22 Halogen Light Source Power: 7.5W Supply Voltage: 5V Connector: FSMA 905 Options PTG-NIR: 10 ml small volume test set, includes POM funnel, stirrer, sample collecting dish, validation cone Dust Hood made from brown coloured Plexiglas, includes front door, vacuum exhauster connection tube Net weight: Gross weight: Packaging: 48 kg 65 kg 900 mm x 750 mm x 750 mm The PTG-NIR is yet not available. The functionality, its data reproducability and also economical sales aspects are still under investigation (Aug. 2010). 41-03200_09.1.0E Page 5 of 5