SeDeM expert system a new innovator tool to develop pharmaceutical forms

Context: The SeDeM expert system is based on the experimental study and quantitative determination of the characterization parameters of powdered substances, the aim being to determine whether a substance is suitable for producing tablets by means of direct compression (DC) technology, thereby reducing the lead time for pre-formulation studies. Additionally, this expert system also provides formulations with a minimum number of excipients.

Objective: We used this system to analyze suitable formulas for the production of orodispersible ibuprofen tablets.

Method: Twenty-one disintegrants and ibuprophen were characterized using SeDeM methodology.

Results: The results indicated that production of ibuprofen tablets by DC would require improvements in the dimension and compressibility factors of the active pharmaceutical ingredient. The expert system analysis provided the specific percentage of disintegrant needed to blend with ibuprofen and a standardized formula of lubricants in order to obtain a powder mix that would successfully produce tablets by DC. The eight formulas proposed by SeDeM were produced and tested in the laboratory.

Conclusion: All eight formulas successfully produced tablets by DC, but only four of them could be considered suitable for use as an orodispersible tablet and accomplishes all the pharmaceutical quality parameters. So, in fact, the use of the SeDeM system reduced the time of medicine’s development and therefore the cost of the activity.     

Te-seeded growth of few-quintuple layer Bi2Te3 nanoplates

We report on a Te-seeded epitaxial growth of ultrathin Bi2Te3 nanoplates （down to three quintuple layers （QL）） with large planar sizes （up to tens of micrometers） through vapor transport. Optical contrast has been systematically investigated for the as-grown Bi2Te3 nanoplates on the SiO2/Si substrates, experimentally and computationally. The high and distinct optical contrast provides a fast and convenient method for the thickness determination of few-QL Bi2Te3 nanoplates. By aberration-corrected scanning transmission electron microscopy, a hexagonal crystalline structure has been identified for the Te seeds, which form naturally during the growth process and initiate an epitaxial growth of the rhombohedral- structured Bi2Te3 nanoplates. The epitaxial relationship between Te and Bi2T% is identified to be perfect along both in-plane and out-of-plane directions of the layered nanoplate. Similar growth mechanism might be expected for other bismuth chalcogenide layered materials.     

Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells

The application of siRNA in gene therapy is mainly limited because of the problems with its transport into cells. Utilization of cationic dendrimers as siRNA carriers seems to be a promising solution in overcoming these issues, due to their positive charge and ability to penetrate cell membranes. The following two types of carbosilane dendrimers were examined: CBD-1 and CBD-2. Dendrimers were complexed with pro-apoptotic siRNA (Mcl-1 and Bcl-2) and the complexes were characterized by measuring their zeta potential, circular dichroism and fluorescence of ethidium bromide associated with dendrimers. CBD-2/siRNA complexes were also examined by agarose gel electrophoresis. Both dendrimers form complexes with siRNA. Moreover, the cellular uptake and influence on the cell viability of the dendrimers and dendriplexes were evaluated using microscopic methods and XTT assay on MCF-7 cells. Microscopy showed that both dendrimers can transport siRNA into cells; however, a cytotoxicity assay showed differences in the toxicity of these dendrimers.     

Human apolipoprotein A-I gene promoter mutation influences plasma low density lipoprotein cholesterol response to dietary fat saturation

Numerous studies have demonstrated an association between polycyclic aromatic hydrocarbons (PAHs) and lymphocyte toxicity. The present study shows that, consistent with its effects on Ca2+ homeostasis, benzo[a]pyrene (BaP) induces apoptosis in Daudi cells. Terminal deoxynucleotidal transferase-mediated dUTP-biotin nick end labeling (TUNEL) analysis at 18 h revealed a significant increase in the number of cells undergoing apoptosis in response to BaP (75%), BaP-7, 8-dihydrodiol (110%), and BaP-7,8-9,10-diol epoxide (BPDE) (215%) over DMSO vehicle control cultures. By 36 h, the trend toward increasing numbers of apoptotic cells continued with the parent compound producing a 125% increase over control values and the 7, 8-dihydrodiol and BPDE metabolites producing 195% and 370% increases over controls, respectively. DNA fragmentation assays demonstrated the presence of internucleosomal cleavage products consistent with the increasing numbers of TUNEL-positive cells responding to PAHs at 18 and 36 h. Analysis of poly(ADP-ribose) polymerase (PARP) protein in BaP- and BaP-7,8-dihydrodiol-treated cells strongly suggested the involvement of cysteine proteases by the appearance of an 85-kD fragment derived from hydrolytic cleavage of PARP, a phenomenon that has been associated with apoptosis in many systems. Immunoblot analysis demonstrated that both BaP and its 7,8-dihydrodiol metabolite affected a pathway involving Bcl-2 and Bax cytosolic proteins. Daudi cells undergoing apoptosis at 36 h in response to 10 microM BaP, the parent compound, expressed moderately reduced amounts of Bcl-2 (78% of vehicle controls). At the same time point, the 7,8-dihydrodiol and BDPE metabolites at 3 microM resulted in Bcl-2 protein expression that was 52% of that seen in vehicle controls. Parallel samples analyzed for expression of Bax protein displayed a 130% increase over vehicle control in Bax expression in response to the parent compound, while the 7,8-dihydrodiol metabolite produced a 257% increase in Bax. Furthermore, the effects on increased Bax expression were observed as early as 3 h after PAH exposure. The apoptotic response to PAHs in Daudi cells was sensitive to 4-h pretreatment with 0.3 microM alpha-naphthoflavone (ANF), a known inhibitor of cytochrome P450. In TUNEL assays of cells exposed to PAHs following pretreatment with ANF, at 18 h there was a significant reduction in the number of cells undergoing apoptosis in response to ANF compared to cells that were not pretreated with the compound. The effect of the parent compound at 18 h was completely blocked with ANF pretreatment, while ANF exerted a relatively weaker, but significant, effect on BaP-7, 8-dihydrodiol-induced apoptosis. With regard to modulation of expression of apoptosis-related proteins, Bax expression was restored to that observed in vehicle-control cultures at all time points tested (3, 18, and 36 h). Bcl-2 expression was most responsive to ANF at later time points following PAH exposure (18 and 36 h); however, Bcl-2 appeared to be more sensitive to the effects of ANF alone. Taken together, these data suggest that modulation of Bcl-2 family proteins, perhaps secondary to altered Ca2+ homeostasis, plays an important role in human B cell apoptosis induced by BaP.     

Common random numbers and multinomial selection

In this paper, we perform empirical evaluation on how common random numbers (CRNs) affect multinomial selection procedures (MSPs) under an indifference-zone probability requirement. The conclusion obrained from this research is that the use of CRNs sharpens MSPs. With the same number of replications, the probability of making a correct select increases when using CRNs.     

Anthocyanin composition of Tempranillo, Garnacha and Cabernet Sauvignon grapes from high- and low-quality vineyards over two years

The anthocyanin composition of Tempranillo, Garnacha and Cabernet Sauvignon grapes over two vintages was studied. Samples were obtained during berry ripening from two vineyards that differed by producing fruit of high and low quality. The proportions of the individual compounds remained practically constant within a single vineyard along the sampling period, the changes in the anthocyanin composition being principally quantitative. Different multivariate statistical methods showed that the anthocyanin profile was primarily determined by variety. This genetic dependence was particularly verified when the sums of the non-acylated glucosides, the acetates and the p-coumaryl derivatives, were analysed. The mean relative content corresponding to these three anthocyanin fractions was always the same within each variety, independently either of the vineyard or the vintage year considered. Relating to the individual compounds, several permanent qualitative differences between vineyards in each variety were also found, although the difference in the total anthocyanin concentration was always much higher.