|
January 2000 |
The Way to the Spray |
||||||
|
|
|
|
Image Therm Engineering of Waltham, MA, has developed a state-of-the-art nonintrusive nasal-inhaler spray characterization system. The system design included a Kodak high-speed digital camera and a Lasiris diode laser sheet generator. The analysis and processing software of the system was fully implemented using LabVIEW and IMAQ Vision from National Instruments of Austin, TX. SprayVIEW is currently being used as a research and development tool for current and pending nasal-spray-based medications at Muro Pharmaceutical of Tewkesbury, MA, while Image Therm seeks FDA approval and patents for the system's novel measurement and analysis techniques. The fluid-dynamic characterization of the aerosol spray emitted by nasal inhalers is crucial in determining the overall performance of the inhaler as a medicinal delivery system to people suffering from various respiratory ailments. Thorough characterization of the spray's geometry has been found to be the best indicator of the overall performance of most nasal inhalers. In particular, measurements of the spray's divergence angle as it exits the inhaler, the spray's cross-sectional ellipticity and uniformity, and the time evolution of the developing spray have been found to be the most representative performance quantities in the characterization of an inhaler design. These measurements are typically used to optimally match the spray pump's performance characteristics with the fluid properties of the liquid medicine solution, resulting in a more cost-effective and efficient product design. But accurate, reliable, and easy-to-use protocols and a system for nasal spray characterization do not exist for these inhalers. These needs were the motivation for this work. The nasal spray testing standard in use today at many pharmaceutical companies involves firing the spray pump at a solid, thin-layer chromatography (TLC) plate. This plate is positioned at a fixed height above the end of the pump's tip. Spray pattern analysis is done by first exposing the particle-covered plate to UV radiation, causing its coating to fluoresce and helping to highlight the spray pattern. Marking instruments and mechanical calipers are then used to draw and measure an outline of the deposited pattern on the plate. Measurements of the pattern's ellipticity in terms of major and minor diameters are recorded. Experience has revealed many problems with this technique, including:
A thorough search of existing technology that could be used or adapted for this system was conducted at the outset of the project. The team finally decided on a hybrid design consisting of a combination of off-the-shelf and custom-made components. The system's basic components are:
National Instruments' software was used to build the SprayVIEW system software because it provided the best mix of image-processing functionality and user interface development tools that would be needed to implement the final custom application. In addition, the SCSI Toolkit for LabVIEW from Icon Technologies of Victoria Park, Australia, helped to provide seamless integration for downloading the digital images from the Kodak SR-500 into the SprayVIEW system. The team chose the Kodak digital camera system because it has a programmable framing rate from 30 to 500 fps at resolutions up to 512 x 480 pixels with 256 grayscales (8-bit). In addition, it has fast on-board memory that allows reliable image captures and a SCSI interface bus for direct downloading of these images to the custom-developed SprayVIEW analysis software running on the host computer. The researchers selected the Lasiris laser sheet generator because it operates in a continuous mode, produces a thin sheet of laser light directly, and favorably matched the spectral response characteristics of the Kodak camera for adequate illumination of the spray particles. Since the duration of a single pumping of the spray is on the order of one second, it is crucial to have accurate synchronization between the spray pump actuator and the camera. The Innova-Systems nasal spray pump actuator was chosen because it is standard equipment at many pharmaceutical companies and could be used to trigger the camera accurately when the spray pump is fired.
The spray pump is first filled with test fluid and inserted into the mouth of the actuator, which has been precalibrated for compression force and duration per company testing guidelines. The camera is set to capture at 500 fps at a resolution of 512 x 240 pixels. The input trigger is armed and set to wait for the actuator to fire. The laser is turned on and its light sheet is focused to a thickness of approximately 1 mm when it illuminates the plane of spray particles. In this configuration, the laser is positioned so that it illuminates a predetermined axial cross section of the spray directly downstream of the spray pump, as shown in Figure 1. The camera is positioned so that it can view the spray pattern from above at angle slightly off-axis to prevent the spray particles from directly impinging on the camera and lens. A calibration target is then temporarily placed in the plane of the laser sheet, and the camera lens is adjusted until the target comes into focus. An image of the focused target is captured with the camera and downloaded to the computer. This target image is used as a basis for calibrating the physical coordinate system of the spray-pattern images and to perform the necessary perspective correction to the images to account for the off-axis viewing angle. The target image is then removed from the scene, and the trigger is fired on the actuator, causing the camera to start capturing the time-evolving images of the spray pattern. This takes about two seconds. When completed, the images are downloaded from the camera into the SprayVIEW system. In this configuration, the laser is positioned so that it illuminates a plane of particles parallel to the flow direction along the centerline of the spray, as shown in Figure 2. The camera is positioned perpendicular to the plane of the laser light's sheet. As in the spray pattern test, the calibration target is temporarily placed in the plane of the sheet and the camera lens adjusted until the target comes into focus. Since in this case the camera views the scene normally, no perspective correction is necessary, so the target image is used solely for calibrating the physical coordinate system of the images of the spray geometry. Again, the target image is removed from the scene, the actuator trigger is fired, and the acquired images are downloaded from the camera into the SprayVIEW system. The SprayVIEW software was designed specifically to combine powerful image processing and analysis functionality with an intuitive and easy-to-use interface for detailed study of spray images by technicians and scientists alike. The software's VCR-like controls and variety of color palettes allow a user to visualize the details and development of the time-evolution of the spray images.
The time-average or summation tool allows a user-selectable range of spray images to be combined to simulate the trajectory of the individual particles in the spray. This key feature allows the 200+ valid images from a typical test to be represented in one image that can be used for measurements of the spray's uniformity, ellipticity, and divergence angle, for example. The summary image is also the closest representative of the TLC-plate technique, and this pseudo-backward compatibility forms a key requirement for FDA approval of the system. Measuring Pattern and Geometry
Spray pattern images are analyzed and processed using the pattern tools. These tools allow a user to specify the major and minor axes of an elliptical pattern template on the summation image. The axis specification is accomplished using interactive cursors that are dynamically linked to line profiles of particle intensity along the axes in absolute and percentage units. The user can adjust the cursors until the most representative elliptical pattern has been specified based on the intensity profiles and computed measurements of the ellipticity ratio, as shown in Figure 3. Once this elliptical template has been specified, the VCR controls can be used to play back the images in the time-evolution of the spray while simultaneously displaying an overlay of the template. This feature allows a user to visualize the time-evolution of the particle distribution and dynamically compare it to the time-averaged pattern of the particles in a very intuitive manner. Spray geometry images are analyzed and processed using the geometry tools. These tools allow a user to specify the vertex and included angle of a set of two intersecting orthogonal lines on the summation image. The line specification is accomplished using interactive cursors that are dynamically linked to line profiles of particle intensity along the lines in absolute and percentage units. The user can adjust the cursors until the most representative line-pattern template has been specified based on the intensity profiles and computed measurements of the divergence angle, as shown in Figure 4. Once again, this line-pattern template can be simultaneously overlaid on the time-evolving images and played back using the VCR controls for comparison purposes. Muro Pharmaceutical and Image Therm Engineering successfully combined their knowledge and experience with nasal-spray drug development, fluid mechanics, high-speed imaging and image processing software to develop the novel SprayVIEW spray characterization system. It allows spray-based-drug developers to characterize the time-evolution, cross-sectional ellipticity, and divergence angle of spray patterns quickly and effectively. The system's nonintrusive optical-based design provides significantly improved measurement performance over the currently accepted TLC-plate-based testing technique. The highly modular hardware and software implementation of the system allows easy customization to meet the needs of a variety of spray-testing applications both in R&D and production environments. For more information, contact the authors of this article, Dino J. Farina, President, and Socratis Kalogrianitis, Software Designer, at Image Therm Engineering, 159 Summer St., Suite 2R, Waltham, MA 02452; (781) 893-7793;e-mail: farina@imagetherm.com.
|
