Radiant energy – Invisible radiant energy responsive electric signalling – Infrared responsive
Reexamination Certificate
1999-05-18
2001-11-13
Hannaher, Constantine (Department: 2818)
Radiant energy
Invisible radiant energy responsive electric signalling
Infrared responsive
C250S339120, C250S339020
Reexamination Certificate
active
06316772
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to an apparatus for determining the concentration of a first component in a mixture of at least two components which have different absorption properties in the IR range.
BACKGROUND ART
In the manufacture of pharmaceutical preparations, an active substance is in many cases mixed with an inactive substance to achieve a sufficient volume of the pharmaceutical preparation and to obtain suitable properties of the pharmaceutical preparation. The substances frequently have the form of powder consisting of a variety of particles. Moreover, it is normally large volumes of powder that are mixed to manufacture a large number of doses of the pharmaceutical preparation. It is then most important for the mixture to be homogeneous so that the concentration of the active substance is the same in all doses, for instance in all tablets, that are manufactured from the mixture.
There is today a tendency towards the active substance being more and more potent, and consequently a smaller and smaller volume of active substance need be added to the inactive substance in mixing. This makes it more difficult to provide a homogeneous mixture. It is also difficult to preserve the homogeneity in the mixtures since pulverulent mixtures tend to form layers.
A further difficulty associated with the homogeneity arises in the manufacture of divisible tablets. Some tablets are formed with a notch indicating that these tablets may be divided to allow the user to take half a dose of the pharmaceutical preparation. For such tablets, the manufacturer must be able to guarantee that the concentration of the active substance is the desired one not only in the tablet in its entirety but also in each half of the tablet.
The homogeneity in a powder mixture can be monitored by sampling the mixture at different points of time. If the concentration of the active substance is the desired in each sample, it is assumed that the mixture is homogeneous and that the concentration in all manufactured doses is correct. Correspondingly, when manufacturing tablets, random sampling of tablets from the manufacturing line is made and the concentration is determined. If the concentration is correct, it is assumed that all tablets have the correct concentration. The concentration of the active substance in powders and tablets is in many cases determined by a wet-chemical or dry-chemical method.
An alternative method of determining the homogeneity in tablets is disclosed in U.S. Pat. No. 5,504,332. According to this patent, a NIR reflection spectrum for a pharmaceutical tablet is generated, the homogeneity of which is to be determined. This spectrum is then compared with an index (recognition index) which has been determined on the basis of spectra of previously analyzed, acceptable tablets to determine whether the homogeneity of the tablet in question is acceptable.
A drawback of this method is that it is slow since it is necessary to generate an entire spectrum for each tablet. Further it is not possible to determine how the active substance is distributed in the tablet. Nor can the method be used to study particles of the size that exists in powders.
Also in other fields in industry, there is a need to monitor the homogeneity in mixtures by measuring the concentration of a component in the mixture.
SUMMARY OF THE INVENTION
An object of the present invention therefore is to provide an improved apparatus for determining the concentration of a first component in a mixture of at least two components.
This object is achieved by an apparatus which has the features defined in claim
1
. Preferred embodiments of the apparatus are recited in the subclaims depended from claim
1
.
More specifically, the invention concerns an apparatus of the type described by way of introduction and characterized by image recording means which are adapted to image the mixture by means of IR radiation to produce at least one image, on the basis of which it is possible to determine the concentration of said first component in the mixture.
This apparatus thus is based on the idea that it is possible to use images and image analysis instead of spectrum and spectrum analysis to determine the concentration in a mixture. This is advantageous since it is a much quicker and much easier operation to record an image than to generate a spectrum which requires that the light be spectrally divided. This results, in turn, in the possibility of analyzing all tablets in the manufacture, which yields a much greater safety than random sampling.
An image further contains position information. The image of the mixture can thus supply information on how the components and, in particular, the active component are distributed in the mixture.
The image recording means can be any means whatever that are sensitive to IR radiation and that render it possible to produce a two-dimensional “IR image”. They may comprise, for instance, a line sensor which produces an image by scanning. They can record one or more images of the mixture, for instance, images that are based on IR radiation at different wavelengths.
The image recording means can be adapted to carry out the imaging by means of IR radiation that is reflected from the mixture or transmitted through the mixture. Sometimes a combination of these alternatives can be advantageous.
The advantage of using reflected radiation is that the position information will be improved so that it will be possible to determine, for instance, the distribution of the interesting component in a tablet or the like where the particles in the mixture are compressed into a unit. The drawback is that the reflected radiation supplies information merely on the particles to a certain level of penetration. IR radiation transmitted through a mixture supplies information on particles at all levels in the mixture. On the other hand, this IR radiation supplies poorer position information since the transmitted light is scattered by the particles on which it falls.
With a view to obtaining clear distinctions between the two components, it is convenient to record the image of the mixture by means of radiation at one or more wavelengths where there is a great difference between the absorption properties of the components. To this end, the image recording means advantageously comprise a filter for selecting at least one wavelength at which the components have different absorption properties. The selection of a suitable wavelength/suitable wavelengths is made individually for each specific substance that is to be monitored. In this manner, a monochromatic image of the mixture is produced.
Alternatively, the image recording means may comprise at least two filters for performing the imaging by means of IR radiation from two different wavelengths ranges to produce an image of the mixture in “IR color” in a manner corresponding to that in which ordinary color images with red, green and blue light are produced.
The IR radiation is advantageously NIR radiation since biologically active substances included in, inter alia, pharmaceutical preparations in most cases have characteristic absorption properties in the NIR range.
An electronic image is composed of a large number of pixels each having one or more intensity values. In an IR image, each pixel has at least one IR intensity value which yields a measure of the intensity of the IR radiation which has fallen on a corresponding point on a sensor in the image recording means. Knowing the absorption properties of the components contained in the imaged mixture in respect of the IR wavelengths involved, it is then possible to determine which pixels represent the different components and, thus, the concentration thereof. The apparatus therefore suitably comprises image processing means which are adapted to determine, with the aid of intensity values for pixels in the image of the mixture, the concentration of said first component in the mixture. The image processing means can advantageously consist of a suitably programmed computer. If the image of the mixtures is monochromatic, the
Agrovision AB
Gagliardi Albert
Hannaher Constantine
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