Image analysis – Applications – Biomedical applications
Reexamination Certificate
2002-09-30
2004-02-17
Mehta, Bhavesh M. (Department: 2625)
Image analysis
Applications
Biomedical applications
C382S128000, C382S168000, C382S170000, C382S255000, C382S302000, C702S027000
Reexamination Certificate
active
06694048
ABSTRACT:
FIELD AND BACKGROUND OF THE INVENTION
The present invention relates to a method for determining physicochemical characteristics of a particulate substance and, more particularly, to a method for generating intra-particle morphological concentration/density maps and histograms of a chemically pure particulate substance by spectral imaging of individual particles of the chemically pure particulate substance and analyzing the spectral images using pattern recognition classification analysis.
In the highly regulated biopharmaceutical industry, an important stage during research and development of a new therapeutic product such as a drug, high-performance chemical, or micro-organism, featuring at least one chemically pure particulate substance either in the raw material(s) and/or in the eventual finished product formulated as a tablet, capsule, caplet, or loose powder, involves extensive and well documented laboratory analytical testing of the physicochemical properties and characteristics of each chemically pure particulate substance. Hereinafter, the term ‘chemically pure particulate substance’ refers to particulate substance featuring one, or a combination of several, chemically pure individual chemical compounds, where the chemically pure particulate substance is typically heterogeneous with respect to physical location or morphological distribution of the concentration and/or density of the at least one chemically pure compound throughout a given sized sample of the chemically pure particulate substance.
Information about the physicochemical properties of each chemically pure particulate substance are needed in a later stage for performing pharmacodynamical studies, involving metabolic and efficacy studies of the therapeutic product when ingested by an animal or human during pre-clinical and clinical studies. Metabolic information about the therapeutic product is needed for designing and evaluating efficacy studies, where the effectiveness of the therapeutic product for performing the indicated therapeutic function in a subject is measured. Ultimately, information and data from the efficacy studies are used for establishing the final formulation and recommended dosage levels of the new therapeutic product for dispensing to the consumer market. Correspondingly, data and information about the final formulation are used for establishing standardized quality control parameters and criteria for full-scale manufacturing of the new therapeutic product.
Full-scale manufacturing of such a new or current, therapeutic product, involves extensive and well documented standardized quality control testing of each chemically pure particulate raw material and/or the chemically pure particulate finished product, according to established quality control and quality assurance parameters and criteria. Similar to the research and development stages of such a product, this involves laboratory analytical testing and classification of the physicochemical properties and characteristics of each chemically pure particulate substance relating to the therapeutic product.
Laboratory analytical testing of such a particulate substance, during research and development stages or during routine finished product quality control testing, typically includes measuring and determining concentration(s) and/or density(ies), and morphological properties and characteristics such as particle size and particle geometry, shape, or porosity distributions of a sample of the chemically pure particulate substance, in a statistically meaningful manner. Typically, such laboratory testing also includes measuring and determining dissolution properties of each applicable or selected chemically pure particulate substance. Dissolution testing provides data and information about the kinetics and thermodynamics of dissolution of a given chemically pure particulate substance in a variety of solvents. As indicated above, such detailed information about the physicochemical properties of each chemically pure particulate substance is valuable and used for either understanding, classifying, or quality control testing pharmacodynamical behavior of the therapeutic product.
It is commonly known in the field of physical chemistry of particulate matter that dissolution properties and behavior of a particle, and therefore, of a sample of particulate substance featuring a plurality of particles, in a liquid medium, either in-vitro or in-vivo, are closely related to and functions of morphological properties and characteristics such as particle size, geometry or shape, and porosity distributions, and, concentration and/or density, of the particulate substance. Thus, measuring and determining data and information about the latter particle properties and characteristics, are useful for highly accurately and reproducibly determining, understanding, classifying, and testing dissolution properties and behavior of the particulate substance. This relationship is clearly applicable to laboratory analytical testing of chemically pure particulate substances extensively performed by the biopharmaceutical industry, as described above.
There are extensive prior art methods, devices, and systems, relating to accurately and reproducibly measuring and determining morphological properties and characteristics of a particulate substance, where these are typically based on imaging the particulate substance. Spectral imaging is currently a widely used technique for imaging particles. In spectral imaging, a particulate substance is affected in a way, for example, excitation by incident ultraviolet light upon the substance, which causes the substance to emit light featuring an emission spectra. Emitted light is recorded by an instrument such as a scanning interferomneter that generates a set of interferogram images, which in turn are used to produce a spectral image, also referred to as a cube image, of the substance. Each cube (spectral) image is a three dimensional data set of voxels (volume of pixels) in which two dimensions are spatial coordinates or position, (x, y), in the substance and the third dimension is the wavelength, (&lgr;), of the imaged (emitted) light of the substance, such that coordinates of each voxel in a spectral image or cube image may be represented as (x, y, &lgr;). Any particular wavelength, (&lgr;), of imaged light of the substance is associated with a set of cube images or spectral fingerprints of the substance in two dimensions, for example, along the x and y directions, whereby voxels having that value of wavelength constitute the pixels of a monochromatic image of the substance at that wavelength. Each cube image, featuring a range of wavelengths of imaged light of the substance is analyzed to produce a two dimensional map of the chemical composition, or of some other physicochemical property of the substance, for example, particle size distribution.
An example of a method and system for real-time, on-line chemical analysis of particulate substances, for example, polycyclic aromatic hydrocarbon (PAH) particles in aerosols, in which the PAH substance is excited to emit light, for example fluorescence, is that of U.S. Pat. No. 5,880,830, issued to Schechter, and manufactured by Green Vision Systems Ltd. of Tel Aviv, Israel, the teachings of which are incorporated by reference for all purposes as if fully set forth herein. In the disclosed method, spectral imaging techniques are implemented to acquire an image and analyze the properties of fixed position PAH particles. As part of this method, air is sampled by means of a high volume pump sucking a large volume of air featuring aerosol contaminated with PAH particles onto a substrate, followed by on-line imaging and scene analysis of the stationary particles.
A method of calibration and real-time analysis of particles is described in U.S. Pat. No. 6,091,843, to Moshe et al., the teachings of which are incorporated by reference for all purposes as if fully Set forth herein. The method described, is based on using essentially the same system of U.S. Pat. No. 5,880,830, for acquiring spectral image
Choobin Barry
Ehrlich Ltd. G. E.
Green Vision Systems Ltd.
Mehta Bhavesh M.
LandOfFree
Method for generating intra-particle morphological... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for generating intra-particle morphological..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for generating intra-particle morphological... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3336954