EFFECT OF THE UNCERTAINTY OF THE STABILITY DATA ON THE SHELF LIFE ESTIMATION OF PHARMACEUTICAL PRODUCTS

The estimated shelf life of a drug product is highly influenced by the variability of the measured data. The fluctuation of the stability data is composed of the manufacturing process variation (batch-to-batch and within batch variability) and of the uncertainty of the analytical method (reproducibility and repeatability). The aim of the paper is to show a calculation method by which all of the variance components can be estimated before commencing the stability study. The effect of the uncertainty on the estimated shelf life is also considered: the expected variance of a single stability time point and the width of the 95\% one-sided confidence limit after 2 storage years are calculated. For the computation the results of the content uniformity test and the validation (specifically the precision study) of the analytical method are used. The applied mathematical method is the analysis of variance. The advantage of the concept is that if the magnitude of the uncertainty is known in advance, one may consider whether the present manufacturing process and analytical method is suitable for the stability study

Gas Antisolvent Fractionation: a New Method to Obtain Enantiopure Compounds, a Case Study on Mandelic Acid

Micronization processes involving supercritical carbon dioxide are rapid methods to produce fine particles. They also might offer the possibility of using less organic solvent than conventional crystallization methods leading to an environmentally friendlier processing. The separation capabilities of such processes are now demonstrated on the diastereomeric resolution of mandelic acid using (R)-1-phenylethanamine as a resolving agent, utilizing the batch type gas antisolvent fractionation as the separation method. A detailed study was conducted on the effects of the operational parameters pressure (12-20 MPa), temperature (35-55 °C) and co-solvent concentration (33-99 mg/ml). At 12 MPa, 35 °C and 99 mg/ml methanol concentration, a selectivity of 0.52 and a diastereomeric excess of 62% was reached. The same operational parameters were applied during the investigation of the recrystallization-based further purification of the diastereomeric salts, applying the resolving agent in molar equivalent quantity to a non-racemic mixture of mandelic acid. It has been found that the more stable (R)-1-phenylethylammonium-(R)-mandelate salt can be purified to de>98% through four additional recrystallization steps following the initial, half-molar equivalent resolution step

Human beta defensin levels and vaginal microbiome composition in post-menopausal women diagnosed with lichen sclerosus

Abstract Human beta defensins (hBDs) may play an important role in the progression of lichen sclerosus (LS), due to their ability to induce excessive stimulation of extracellular matrix synthesis and fibroblast activation. The genetic ability of the individual to produce defensins, the presence of microbes influencing defensin production, and the sensitivity of microbes to defensins together regulate the formation of an ever-changing balance between defensin levels and microbiome composition. We investigated the potential differences in postmenopausal vaginal microbiome composition and vaginal hBD levels in LS patients compared to non-LS controls. LS patients exhibited significantly lower levels of hBD1 (p = 0.0003), and significantly higher levels of hBD2 (p = 0.0359) and hBD3 (p = 0.0002), compared to the control group. The microbiome of the LS patients was dominated by possibly harmful bacteria including Lactobacillus iners, Streptococcus anginosus or Gardnerella vaginalis known to initiate direct or indirect damage by increasing defensin level production. Our observations highlight that correcting the composition of the microbiome may be applicable in supplementary LS therapy by targeting the restoration of the beneficial flora that does not increase hBD2-3 production

Preparation and Analysis of Polar Hawthorn Berry Extracts, Industrial Application in Poultry Processing

For years, it is an actuality in the poultry processing industry, that the body and the cardiovascular system of the chickens are not strong enough due to the shortened rearing time. This induces, that the quality of the chicken breast is not appropriate for selling, since during the processing procedure, frequently blood spots appear inside the meat. These damaged parts need to be removed, causing huge economic loss. In this paper a solution for this problem is searched using hawthorn, a traditional herb, with well-known beneficial effects to the cardiovascular system. Improvement of the product quality and the reducing amount of the removed meat are supposed by applying a treatment with a polyphenol-rich drinking tincture made from the plant. Beside the preparation of the drinking liquid, including pretreatment, extraction and dilution steps, chemical analysis of the phenolic compounds is also conducted. The result of the drinking test shows that the extent of the blood spots, and thus the quantity of the "cut off" meat decreased significantly, however the reduction of the meat weight and a slight change in the death rate are also needed to take into consideration. It has been found, that the total phenolic contents of the berry are similar to literature data, while they show moderate antioxidant efficiency. Several phenolic acids, procyanidins and flavonoids were identified as the main phenol compounds of the applied extract