Pertti Silfsten

Detection of porosity of pharmaceutical compacts by terahertz radiation transmission and light reflection measurement techniques

We report on the non-destructive quantification of the porosity of pharmaceutical compacts (microcrystalline cellulose tablets) by using both optical and terahertz techniques. For the full analysis of the porosity of pharmaceutical tablets, the results obtained in both cases have shown that optical and terahertz techniques are complementary. The intrinsic refractive index of microcrystalline cellulose was estimated using the effective refractive index obtained from the time delay of the THz pulse together with the Bruggeman model for effective media. Once this intrinsic refractive index is known, the unknown porosity of the tablet can be estimated with the aid of the measured effective refractive index as well as the thickness of the pharmaceutical tablet. The method was tested using a set of thirteen tablets having different porosities. It is shown that the error in the estimation of the unknown tablets porosity is less than 1%. In addition, surface roughness was measured by using an optical interferometer and gloss by using a diffractive-optical-element based glossmeter. The measurement was achieved by scanning the tablets with a probe beam and detecting the reflected light. The surface roughness and gloss data show relatively good correlation with the porosities of the tablets.

Color sensitive retina based on bacteriorhodopsin.

Bacteriorhodopsin (BR), a membrane protein of a microorganism Halobacterium salinarium has been studied since the 80s as a potential material for information technology. The information processing applications of BR employ either photochromic or photoelectric properties of the protein. In this study we discuss about design principles and describe our study of the use of bacteriorhodopsin as a sensor material for a color sensitive artificial retina. This retina includes low-level processing of input information. The design of a color sensitive matrix element, the self-organizing color adaptation algorithm and a system model for the retina are presented.

Non-contact weight measurement of flat-faced pharmaceutical tablets using terahertz transmission pulse delay measurements.

By measuring the time delay of a terahertz pulse traversing a tablet, and hence its effective refractive index, it is possible to non-invasively and non-destructively detect the weight of tablets made of microcrystalline cellulose (MCC). Two sets of MCC tablets were used in the study: Set A (training set) consisted of 13 tablets with nominally constant height but varying porosities, whereas Set B (test set) comprised of 21 tablets with nominally constant porosity but different heights. A linear correlation between the estimated absolute weight based on the terahertz measurement and the measured weight of both sets of MCC tablets was found. In addition, it was possible to estimate the height of the tablets by utilizing the estimated absolute weight and calculating the relative change of height of each tablet with respect to an ideal tablet. A good agreement between the experimental and the calculated results was found highlighting the potential of this technique for in-line sensing of the weight, porosity and the relative change in height of the tablets compared to a reference/ideal tablet. In this context, we propose a quantitative quality control method to assess the deviations in porosity of tablets immediately after compaction.

A Study on the Resolution of a Terahertz Spectrometer for the Assessment of the Porosity of Pharmaceutical Tablets

In this study, the resolution of a time-domain terahertz spectrometer for tablet porosity measurements was estimated using two sets of pharmaceutical tablets. One set consisted of tablets with constant thickness and with porosity as a variable. The other set consisted of tablets with variable thickness and only a relatively small change in porosity. The set with constant thickness was used for the calibration of the terahertz (THz) spectrometer for the porosity measurements, and the resolution of the terahertz spectrometer was estimated using the set with different thicknesses and slightly different porosities. It was shown that a time-domain THz spectrometer is a sensitive device that allows monitoring of minute changes in the porosity of pharmaceutical tablets by detecting the time delay of the THz pulse, which is attributable to different refractive indices within the tablet.

Computational theory of color transparency: recovery of spectral properties for overlapping surfaces

A computational theory of color transparency for color images containing X junctions is described. This theory is based on physical models of color transparency under conditions of additive or subtractive color mixture that describe the relationship among four colors at an X junction. Algorithms are derived for recovering transmittance and surface reflectance functions of a transparent medium from a set of sensor responses at an X junction. The algorithms are based on the ability to describe surface reflectance and transmittance functions by using a linear combination of orthogonal basis functions. We also address algorithms for determination of depth ordering of overlapping surfaces and the type of color mixture by checking the physical realizability of recovered functions.

Modified bacteriorhodopsins as a basis for new optical devices

The photochemical properties of various bacteriorhodopsin analogs in water suspensions and PVA films have been studied and their promise for technological purposes (especially as a basis for colour-imaging and -recognition devices) is shown.

Kramers–Kronig analysis on the real refractive index of porous media in the terahertz spectral range

We present a terahertz time-domain experimental technique for the detection of scattering from porous media. The method for detection of the scattering enables one to make a decision when Fresnel or Kramers-Kronig (K-K) analysis can be applied for a porous medium. In this study the real refractive index of a tablet is calculated using the conventional K-K dispersion relation and also using a singly subtractive K-K relation, which are applied to the extinction coefficient obtained from the Beer-Lambert law. The advantage of the K-K analysis is that one gets estimates both for absolute refractive index and also dispersion of the porous tablet, whereas Fresnel analysis provides only the absolute value of the index.

An optical method for continuous monitoring of the dissolution rate of pharmaceutical powders

Monitoring systems providing fast and reliable, even on-line data, from a distinct process stage or final product are needed in drug development, from the early stages of drug discovery until the drug product manufacturing procedures. This includes also processes involving solid particles, such as drug dissolution. However, the existing in vitro drug dissolution test methods suffer limitations, such as long sampling times of 30-60s and thus the inability to be adapted to continuous monitoring, time consuming sample preparation and consumption of large amounts of reagents. In this study, an optical method for monitoring the dissolution rate of pharmaceutical powders was evaluated with model drugs having different dissolution rates. The measuring system consisted of a laser source, light detector, oscilloscope, magnetic stirrer and sample vessel. The intensity of laser light transmitted through the dissolution medium was recorded and displayed by the oscilloscope. Dissolution curves were produced by fitting the raw data with mathematical functions. The optical method was found to be resource-saving, reliable and capable of detecting differences in even rapid dissolution rates of drug compounds. This technique might have targets of application in real-time monitoring of processes in many different sectors, including the pharmaceutical industry.

Color-sensitive biosensors for imaging

Research on an artificial retina is mainly concentrated on the design of silicon based integrated circuits, where the spatial structure of the circuit and the electrical design of a pixel plays the main role. Color sensitivity has not been an issue, or it is realized by using separate filters in front of the circuit. There are only few studies concerning an artificial retina based on a biomolecular structure. In this study we describe some optically active biomolecules, which are potential materials for construction of an artificial retina. We use bacteriorhodopsin and its variants. This protein is produced by a bacterium, Halobacterium salinarium. The protein is closely related to the light sensitive molecule of human retina. The studied molecules have different wavelength properties with each other and when mounted on a polyvinylalcohol film, they produce an electric signal from optical input. We have produced a set of protein films with different wavelength properties and we report the basic characteristics of these films, referring them as basic elements of an artificial retina. The design principles of a biomolecule based artificial retina is also discussed.

Dispersion relations for evaluating the complex refractive index of medium without the information of its thickness

A general method to obtain the complex refractive index of a medium from absorbance, or alternatively from optical path length data, without knowing the sample thickness is proposed. The method can be formulated in any spectral range and it is here applied particularly in the terahertz spectral range to both simulated and experimental data. The key idea is the derivation of nonconventional dispersion relations that partly resemble traditional Kramers-Kronig relations. The method is shown to work well in extracting the complex refractive index of a drug system and a precipitated calcium carbonate.