PHARMAVISION 830 AUTOMATED PARTICLE SIZE AND SHAPE MEASUREMENT

Transcription

1 PHRMVISION 830 UTOMTED PRTICLE SIZE ND SHPE MESUREMENT

2 INTRODUCTION 2 Particle Shape Characterisation new parameter for process understanding PharmaVision 830 It is well known that particle shape as well as size distribution affects the physical characteristics and behaviour of particulate materials. In the pharmaceutical, toner and powder coating industries for example, quantifying particle shape as well as size is already highly desirable. Many other industries are assessing the impact of shape on process robustness and product quality, but are hampered by the lack of a universal shape analysis technique. Characterization of particle shape has always been difficult to achieve in a routine way.traditionally, particle shape measurements have involved microscopy because of the large amount of information it provides. However, for statistical significance large numbers of particles need to be characterized and this, combined with sample preparation is very time consuming. Microscopy is often considered to be an absolute method, which can be used to verify or calibrate other techniques. The PharmaVision 830 enables reliable, repeatable and routine characterisation of particle size and particle shape using automated imaging techniques. Comprehensive particle characterization data is generated in a short period of time. Extensive information about particle shape is acquired from the analysis of a large number of particles, displays of size and shape data are supported by images of all the particles to provide further visual understanding of the measurement data. Measurement Principle The PharmaVision 830 is an automated vision system for the size and shape analysis of dry powders.the system is easy to use, has a wide dynamic range and provides a variety of shape parameters. Optics The PharmaVision 830 is an automated vision system; specially designed and prepared glass slides are placed on a sample tray underneath a CCD video camera. linear actuator automatically moves the camera across the sample tray and takes digitised video images. zoom lens allows the user to analyze particles in the range 5µm 2000µm. n optional high magnification unit enables particles in the range 0.5µm 500µm to be analyzed. Small apertures are used to increase the depth of field whilst maintaining the required resolution and detail for particle size analysis. Zoom lens system High magnification system 50µm 500µm Depth of field showing 500µm and 50µm particles in focus Camera Scanning The video camera scans the sample in a pre-programmed (user defined) way by moving in the x and y directions. For each movement a new image is acquired. Scanning is programmed such that adjacent fields have a sufficient degree of overlap. Conventional image analysis ignores particles touching the edge of the acquired image biasing the results to smaller sizes. By collecting overlapping images this bias is removed.the coordinates of each particle are logged, preventing particles from being counted twice. Particle segmentation Particle size distribution Calibration The instrument automatically calibrates itself prior to an analysis by the measurement of both the light intensity and a precision grating with a known number of lines per mm.the instrument re-checks the calibration once the measurement is complete, to ensure that nothing has changed during the analysis. Image Processing The particles in the raw video image are first separated from the background (threshold) and a novel algorithm then divides any touching particles (segmentation). This process is automatic and takes place many times a second.the images are then sized and the software makes direct measurements of pre-defined morphological parameters (mean diameter, circle equivalent diameter, contour/area, roundness, convexity, length, maximum length, width, volume, area).these are displayed as real-time histograms on the screen as either number or volume distributions.the PharmaVision 830 typically analyzes around 20,000 particles in approximately 10 minutes.the total numbers of particles analyzed is user defined. Verification and Validation The PharmaVision 830 has a full validation package including life cycle documentation.the documentation is supplied on a CD, which enables users to adapt it to fit in with their own documentation. Reference slides are available for the rapid verification of instrument performance for both zoom and high magnification optics. The reference slides are certified and are traceable to NIST standards. 3

3 THEORY ND PRCTICE 4 Sample Preparation Optimum conditions for analysis are achieved when the particles are dispersed on the glass slides in a mono-layer.with manual sample preparation this is difficult to achieve.the Sample Preparation Device has been designed to automate the dispersion of powders as a mono-layer onto microscope or glass slides.this device uses compressed air to disperse the sample and to break up agglomerates by forming a particle cloud in a sealed chamber.the cloud settles on the microscope slide. Full control of the degree of dispersion is achieved by adjustment of the cycle time, injection pressure and sample injection time. Software The software is easy to use and has been designed for use in GMP regulated R & D or QC environments.the user can elect to store either summary results or all the images of the particles including all the morphological data.the data generated can be exported to other applications for further analysis. Macros can be written to define particles based on a combination of parameters to identify fibres or agglomerates for example.this facility can also be used to discard or classify particles. Invalid results are marked and the original data can not be changed. The sub-analysis option enables size distributions measured at different magnifications to be merged together. Particles dispersed at high pressure by sample preparation device. Particles dispersed at low pressure by sample preparation device. Particles manually dispersed on a microscope slide. Sample Preparation Device View of particle images and single particle showing its morphological data Morphological Parameters The PharmaVision 830 provides a comprehensive range of morphological parameters as standard; custom parameters can also be generated. The major axis is the vector that passes through the centre of mass of the particle, around which the two dimensional projection of the particle would generate the smallest rotational energy if spun around that axis. Mean Diameter The radius from the centre of mass to the edge of the particle is measured every 3. The diameter is calculated from the mean value of these measurements. Circle Equivalent Diameter The diameter of the particle is equal to the diameter of a circle with the same area as the particle. Particle area () = Circle area () Diameter rea The visual projected surface area of the particle (). Roundness Roundness is a measurement of the length/width relationship, with values in the range 0-1. perfect circle has roundness 1.0, while a needle shaped object (b) has roundness close to 0. Centre of mass (b) Major axis 3 Major axis Max Distance Convexity Convexity is the object area divided by the area enclosed by an imaginary rubber band wrapped around the object.the convexity has values in the range 0-1. convex shape (a) has convexity 1.0, while a concave shape (b) has a lower value, close to 0. Convexity = B + B Width Contour/rea Contour/rea is the length of the object s perimeter divided by it s area. Contour/rea is proportional to surface area by volume. Length Minor axis Volume The calculated object volume. The volume V is defined as: (2ad) V = 3 where a is the object area and d is the object s mean diameter. Width ll possible lines from one point of the perimeter to another point on the perimeter are projected on the minor axis.the maximum length of these projections is the width of the object. Max Distance The maximum distance for a particle is the maximum distance found within the particle. Length ll possible lines from one point of the perimeter to another point on the perimeter are projected on the major axis.the maximum length of these projections is the length of the object. 5

4 PPLICTIONS 6 pplications in the Pharmaceutical Industry "Particle Shape Characterisation New Parameter for Process Understanding" The PharmaVision 830 provides accurate shape and size data from direct sample measurements; giving a greater insight into process dynamics.this can assist with the optimisation and control of the process, increasing product quality and reducing cycle times. Greater insight and process understanding is obtained when a number of different parameters (size, shape and surface area) are combined and correlated against process variations. Successful correlation will reveal new ways to monitor product quality, resulting in increased process robustness, better product quality and lower costs. Understanding Process Robustness Understanding the physical characteristics of pharmaceutical ingredients is one of the most important tasks when producing such materials. ctives are very well defined and controlled. However, in many cases a major part of the final formulation consists of excipients that are less well defined and controlled. Most major pharmaceutical companies have global manufacturing programmes, using the same formulations, processes and specifications, ideally producing the same product, but variations arise.this implies that the analytical methods employed are not sensitive enough to detect any variations.the PharmaVision 830 can be used to gain a greater understanding of the way major excipients interact, and identify the origin of the differences. By examining the data generated and correlating it with the process and its variations has provided a far greater understanding of the importance of setting detailed specifications of physical parameters. These examples show that with the introduction of new measurement techniques with higher sensitivity previously unknown variations can be identified.these variations contribute to a reduction in process robustness. Particle Shape The Key Difference By being able to monitor the shape of particles in a substance it will be easier to predict how the material will process. Shape factors can also give early indications of impurities, for example, polymorphs or potential flowability problems. Supplier Variations Many different companies are involved with the supply of excipients. significant variation in number mean particle size of a commonly used excipient was found at different sites.yet all the sites are working to the same specifications. Most companies use volume data to set specifications this focuses on the large particles where the mass is distributed. Number distributions on the other hand look at the size of particles, which are found in the largest proportions and thus focus on the fine material. It was found that it is the number distribution that is critical in determining the processability of the different grades. Using the PharmaVision 830 enables meaningful size/shape specifications to be set for key ingredients. Surface ctivity Surface rea Measurements Many ingredients in a pharmaceutical blend are surface active in this case surface activity is related to the surface area and not particle size. Measuring surface area is often a time consuming process.the PharmaVision 830 generates a relative measure of the surface area. ssessment of the Relative Proportion of Fines The PharmaVision 830 displays both number and volume distributions. Understanding the relative quantities of fine materials often contains information to understanding process problems. Fine materials tend to create more agglomerates thus changing the matrix of the formulation. Being able to use the actives and excipients with the right size shape distributions at the earliest stage is a key factor for process stability and blending efficiency and can help to reduce cycle times. Foreign Particle nalysis novel application has been developed that automates the often time-consuming task of counting and determining the number of foreign particles on a filter or membrane. Regulatory authorities often require such tests when submitting new drug applications. In approximately 10 minutes a 47mm Ø filter can be scanned and the number of particles above and below a certain size limit reported. larm limits can be set so the user will get a simple pass or fail message. ll the particle images are retained and it is potentially possible to identify the source of contamination. PharmaVision 830 Technical Specifications Technical Specifications Measurement Technique utomated Image nalysis Illumination Halogen Lamp Transmitted Optics Zoom Lens Magnification 0.75X 7.5X Particle Size Range 5µm 2000µm High Magnification Unit X5 objective Particle Size range 5µm 500µm X10 objective Particle Size range 1.5µm 100µm X20 objective Particle Size range 0.5µm 15µm Sample Presentation Plate 120mm x 120mm Recommended for particles over 100µm Sample Presentation Plate 76mm x 26mm Recommended for particles under 100µm Maximum Scanning rea 100mm x 100mm Reference Slide (NIST traceable) 5µm 2000µm Reference Slide (NIST traceable) 1.5µm 64µm Optional pplications Sub-analysis Combination of Sub-analysis enables size distributions measured at different magnifications to be merged together. Quantification of Foreign Particles Enables accurate quantification of foreign particles includes application software, sample plate for foreign particle analysis, 47mm Ø filter paper fitting. Requirements Minimum Computer Specification Pentium III processor 800 MHz, 20 GB Disc, 128 MB RM, 24X CD-ROM, LN card, (supplied with system) 1 Parallel port, 1 serial port, 2 PS/2 Connectors, VG connector, 2 PCI slots. Windows NT operating system. Operating Environment Temperature: 15 C 40 C Humidity: 35 80% Requirements Main Unit Sample Preparation Device Dimensions: 500mm (w) x 700mm (h) x 600mm (d) 380mm (w) x 640mm (h) x 460mm (d) Weight 75kg 24kg Power V 24V DC 50/60Hz Compressed ir Pressure N/ MPa (3 16 bar) 7

5 Malvern service and support Malvern Instruments seeks innovation, not only in product design and development, but in every area of business. s many of our systems are used in highly regulated environments, product validation and R & D traceability are key commitments to customers.we have achieved ISO9001 with TickIt accreditation and are able to provide full traceability of changes in software and design. pplications expertise Malvern Instruments trained specialists are available in more than 50 countries to assist with applications development and to advise on and analyze difficult samples.we have our own laboratory facilities and extensive applications expertise derived from our work and that of our users. Malvern application laboratories in Europe, North and South merica routinely run thousands of samples per year. Service Support Comprehensive service support is provided across the entire range of Malvern Instruments products, in all areas.telephone support is always available from the Malvern Help Desk and a variety of service packages can be tailored to meet the specific needs of individual customers.the development of after-sales remote diagnostics means that in many cases Malvern service specialists can access and control systems via standard telephone lines in order to minimize downtime and reduce costs. The Malvern Instruments Range Strategic lliance Malvern Instruments Ltd and PharmaVision Systems B have entered into a strategic alliance that encompasses an exclusive distribution agreement for Malvern Instruments. It allows for the collaboration between the two companies on future product development and the implementation of a joint strategy aimed at solving particle-processing problems in the pharmaceutical industry. Full Range The PharmaVison 830 forms part of Malvern Instruments extensive range of particle characterisation systems, which offers particle characterisation instruments for use both in the laboratory and on the process line.the range includes the Mastersizer range for particle size analysis: Zetasizer instruments for dispersion stability applications; the HPPS for the size analysis of dispersions of micron sized particles and solutions of subnanometer molecules; the Ultrasizer for particle size measurement in concentrated systems; Spraytec for particle size measurement of aerosols and sprays; the Sysmex FPI-2100 for size and shape characterization and Insitec for on-line particle size analysis. Designed & produced by C Force Communications Limited, Hungerford, UK. Malvern Instruments Limited Enigma Business Park Grovewood Road Malvern Worcester WR14 1XZ U.K. Tel: +44 (0) Fax: +44 (0) Malvern Instruments Inc. 10 Southville Road Southborough M U.S.. Tel: +1 (508) Fax: +1 (508) Malvern Instruments Japan. SORIO-3, 6th Floor Sakaemachi Takarazuka, Hyogo Japan Tel: +81 (0) Fax: +81 (0) Malvern Instruments GmbH Rigipsstraße Herrenberg Germany Tel: +49 (0) Fax: +49 (0) Malvern Instruments S.. Parc Club de L Université 30, Rue Jean Rostand Orsay Cedex France Tél: +33 (1) Fax: +33 (1) Malvern Instruments Nordic B Box 15045, Vallongatan UPPSL Sweden Tel: +46 (0) Fax: +46 (0) Ref: MRK HR 8