Nano- and microcrystals of griseofulvin subcutaneously administered to rats resulted in improved bioavailability and sustained release

Griseofulvin is a commonly used antifungal agent which is administered per oral (p.o.). The oral administration route, however, shows rather low bioavailability. The aim of this study was to improve the bioavailability and to evaluate and interpret the pharmacokinetic profiles after subcutaneous (s.c.) administration of crystalline griseofulvin nano- and microsuspensions. Both formulations were injected at 5 and 500 µmol/kg to rats. For the lower concentration, the profiles were similar after s.c. injection but extended as compared to p.o. administration. For the higher concentration, injection of microsuspension resulted in a maintained plateau whereas the nanosuspension resulted in an obvious peak exposure followed by extended elimination. Both suspensions showed improved exposure with dose. The differences in peak exposures between nano- and microparticles, at the high dose, were mainly ascribed to differences in dissolution rate, experimentally determined in vitro, using spectroscopic methods. The extended appearance in the circulation may depend on the physicochemical properties of the compound and the physiological conditions at the injection site. The bioavailability was improved for both formulations compared with an orally administered nanosuspension, suggesting the s.c. route to be a preferred administration option for compounds with low oral bioavailability regarding both overall exposure and extended efficacy.     

Effect of Microencapsulation of Dietary Oil on Postprandial Lipemia

ABSTRACT: Microencapsulation is increasingly applied to dietary oils, but only limited information is available about the effect on bioavailability. The aim of the present study was to evaluate the bioavailability of microencapsulated vegetable oil from a liquid food product in a clinical trial. Another aim was to compare the suitability of sodium octenyl succinate starch (SOSS) and oat starch aggregate (OSA) in sustained release of a vegetable oil. Twenty-four healthy young men were recruited and randomly allocated into 1 of 3 groups (A, B, C). All subjects consumed 2 liquid test meals, which differed only with respect to microencapsulation. Groups A and B consumed berry juice or fermented oat drink, respectively, containing either non-encapsulated or SOSS-encapsulated blackcurrant seed oil (BCO). Group C received sea buckthorn oil (SBO) encapsulated with SOSS or OSA. Blood samples were collected at 0,30,60,90,180,270, and 360 min after the meal, and chylomicron-rich (CM-rich) fraction was separated for subsequent triacylglycerol (TAG) analysis. Microencapsulation increased the glycemic response. SOSS-encapsulated BCO resulted in a similar CM-rich TAG response as non-encapsulated BCO, indicating that the SOSS-encapsulated oil was fully bioavailable. OSA-encapsulation had a similar bioavailability. The lipemic response of subjects who consumed the oil mixed in the fermented oat drink was higher than that of other subjects. This most likely resulted from the slightly higher fat and energy content of the fermented oat drink compared with berry juice. Contrary to expectations, the use of OSA in microencapsulation did not result in sustained release.     

Influence of origin,harvesting time and weather conditions on content of inositols and methylinositols in sea buckthorn (Hippophaë rhamnoides) berries

Inositols and methylinositols play an important role in human physiology. Inositols and methylinositols in berries of three subspecies of sea buckthorn (Hippophaë rhamnoides) were analysed using gas chromatography combined with a flame ionisation detector and mass spectrometry. The wild Chinese berries (H. rhamnoides ssp. sinensis) contained higher levels of l-quebrachitol (1l-2-O-methyl-chiro-inositol) and methyl-myo-inositol (average 615 and 58 mg/100 ml juice, respectively) than the Finnish (H. rhamnoides ssp. rhamnoides, 276 and 11 mg/100 ml juice, respectively) and the Russian (H. rhamnoides ssp. mongolica, 228 and 16 mg/100 ml juice, respectively) berries (P < 0.001). The content of myo-inositol was higher in the Chinese and the Russian berries than in the Finnish berries (26 and 20 mg/100 ml juice vs. 8 mg/100 ml juice, P < 0.001). In the Chinese berries, the contents of methyl-myo-inositol and l-quebrachitol increased, whereas that of myo-inositol decreased from late September to late November. The content of the l-quebrachitol in the Chinese berries correlated negatively with the air temperature and the number of frost-free days, suggesting a possible role of the compound in the cold resistance of sea buckthorn.     

Malolactic fermentation in sea buckthorn (Hippophaë rhamnoides L.) juice processing

Malolactic fermentation (MLF) traditionally used in winemaking was applied to sea buckthorn to reduce the high sourness of the berry juice. Chemical and microbiological aspects, as well as sensory properties of the juice during MLF were studied in order to develop an optimal process. In 1:1 water diluted juice with malic acid content of 15 g/l and pH 2.8, efficient conversion of l-malic acid to l-lactic acid was achieved with direct inoculation of unadapted Oenococcus oeni at a cell density of 10⁹ CFU/ml. The rapid malic acid degradation was performed by non-growing bacterial cells without loss of sugars, vitamin C, or pulp oil. More than 50% of the initial malic acid was metabolized to lactic acid and CO₂ already in 12 h of fermentation and a significant decrease in sourness and astringency was noticed. In 24 h fermentation, pH value was increased to 3.1 and only 3 g/l malic acid remained in the juice. Prolonged fermentation had only minor effect on malolactic reaction, but off-flavor of the juice began to increase.     

Flavonol glycosides in wild and cultivated berries of three major subspecies of Hippophaërhamnoides and changes during harvesting period

Flavonol glycosides are an important group of bioactive components of sea buckthorn (Hippophaë rhamnoides). The content and profile of flavonol glycosides of some major subspecies and most cultivars as well as the variation amongst the harvesting years and dates are largely unknown. This study investigated flavonol glycosides in wild berries of two major subspecies H. rhamnoides ssp. rhamnoides and ssp. sinensis and berries of eight cultivars of ssp. rhamnoides and mongolica by reverse phase high performance liquid chromatography combined with diode array detection. The major flavonol glycosides were isorhamnetin-3-O-glucoside-7-O-rhamnoside, isorhamnetin-3-O-rutinoside, isorhamnetin-3-O-glucoside, isorhamnetin-3-O-sophoroside-7-O-rhamnoside, quercetin-3-O-rutinoside, quercetin-3-O-glucoside and quecertin-3-O-sophoroside-7-O-rhamnoside. The total content of flavonol glycosides fell in the range of 27–130 mg per 100 g fresh berries with considerable variation amongst the origins and the harvesting years. Compared with the berries of ssp. sinensis and ssp. mongolica, the berries of ssp. rhamnoides contained high levels of isorhamnetin-3-O-glucoside-7-O-rhamnoside and isorhamnetin-3-O-glucoside and lower levels of quercetin-3-O-rutinoside and quercetin-3-O-glucoside. In the wild berries of ssp. sinensis, the contents of flavonol glycosides reached maxima around late September to early October and decreased thereafter, whereas a general decreasing trend was seen in the cultivated berries of ssp. rhamnoides from the end of August to the end of October.     

Variability in oil content and fatty acid composition in wild northern currants

Seed oils of wild berries of alpine currant (AC) and northern redcurrant (NRC) were investigated. Oil contents of AC and NRC varied between 4.9 % and 9.7% and between 12.8% and 38.5%, respectively. The proportions of α-linolenic, γ-linolenic and stearidonic acids were higher in NRC (means of 21.7, 12.3 and 5.4%, respectively) than in AC (16.8, 8.6 and 3.0%). The growth areas of NRC can be divided into two distinct groups according to the proportions of different polyunsaturated fatty acids. Oil content of NRC correlated negatively to the proportion of linoleic acid and positively to that of stearidonic acid. There were significant correlations between all polyunsaturated fatty acids in NRC but correlations were less obvious in AC. Interestingly, the correlation between linoleic and γ-linolenic acids was positive in NRC but negative in AC. α-Linolenic and stearidonic acids showed positive correlations in both species. In NRC the synthesis of triunsaturated fatty acids is directed either towards α-linolenic or γ-linolenic acids. Results showed great potential in NRC and AC for plant breeding due to the natural variation in the content and composition of the seed oils for functional nutrients. Received: 20 August 1999 / Revised version: 29 October 1999     

Extension of Affine Shape

In this paper, we extend the notion of affine shape, introduced by Sparr, from finite point sets to more general sets. It turns out to be possible to generalize most of the theory. The extension makes it possible to reconstruct, for example, 3D-curves up to projective transformations, from a number of their 2D-projections. An algorithm is presented, which is independent of choice of coordinates, is robust, does not rely on any preselected parameters and works for an arbitrary number of images. In particular this means that a solution is given to the aperture problem of finding point correspondences between curves.