Agglomeration of ibuprofen with talc by novel crystallo-co-agglomeration technique

The purpose of this research work was to obtain directly compressible agglomerates of ibuprofen with talc by a novel crystallo-co-agglomeration (CCA) technique, which is an extension of spherical crystallization. Ibuprofen-talc agglomerates were prepared using dichloromethane (DCM)-water as the crystallization system. DCM acted as a good solvent for ibuprofen as well as a bridging liquid for agglomeration of crystallized drug with talc. The agglomerates were characterized by differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy and were evaluated for tableting properties and for drug release. The process yielded spherical agglomerates containing ∼95% to 96% wt/wt of ibuprofen. Agglomerates containing talc showed uniform distribution of hydroxypropylmethylcellulose and decreased crystallinity, and deformed under pressure. The miniscular form of ibuprofen and the hydrophobicity of talc governed the drug release rate. The batch containing a higher proportion of talc showed zeroorder kinetics and drug release was extended up to 13 hours. The CCA technique developed in this study is suitable for obtaining agglomerates of drug with talc as an excipient.     

Delayed luminescence: a novel technique to obtain new insights into water structure

Fully understanding the structure of water is a crucial point in biophysics because this liquid is essential in the operation of the engines of life. Many of its amazing anomalies seem to be tailored to support biological processes and, during about a century, several models have been developed to describe the water structuring. In particular, a theory assumes that water is a mixture of domains constituted by two distinct and inter-converting structural species, the low-density water (LDW) and the high-density water (HDW). According to this theory, by using some particular solutes or changing the water temperature, it should be possible to modify the equilibrium between the two species, changing in this way the water behavior in specific biological processes, as in governing the shape and stability of the structures of proteins. In this work, we assess the possibility of obtaining information on the structures induced in water by specific salts or by temperature by measuring the delayed luminescence (DL) of some salt solutions and of water in the super-cooled regime. Previous works have demonstrated that the delayed luminescence of a system is correlated with its dynamic ordered structures. The results show significant DL signals only when the formation of LDW domains is expected. The measurement reveals a similar activation energy for the domains both in aqueous salt solutions and super-cooled water. It is worth noting that the time trend of DL signals suggests the existence of structures unusually long-lasting in time, up to the microsecond range.     

A novel strategy to obtain a hyaluronan monolayer on solid substrates

The aim of this study was to find a novel simple method to obtain polysaccharide ultrathin layers on solid substrates to investigate the interaction between the surface and the biological environment. A Hyaluronan (Hyal) monolayer with a well-defined chemistry was obtained by exploiting the capability of organosilanes to spontaneously adhere onto glass surfaces. A silane alkylic chain was conjugated with Hyal, and the derivatized polysaccharide was allowed to spontaneously adhere onto a glass surface. The elemental analysis of the modified polysaccharide demonstrated that one out of five disaccharide units was conjugated with the alkyl silane chain, corresponding to a substitution degree of the carboxylate groups of approximately 20%. The film of the modified polysaccharide was characterized by means of X-ray photoelectron spectroscopy (XPS), water contact angle, and atomic force microscopy (AFM) measurements. XPS analysis demonstrated that we obtained a Hyal layer with a thickness of about 2.0 nm corresponding to a Hyal monolayer. The Hyal-coated surfaces appeared to be rather smooth and highly hydrophilic and showed significant resistance to nonspecific cell adhesion.     

Monitoring ibuprofen release from multiparticulates: In situ fiber-optic technique versus the HPLC method: A technical note

Summary and conclusions  The results from the linearity test showed that the automated FOPS method was linear and reproducible in predicting ibuprofen concentrations, as was shown by a high R² and low %RSD over a range of concentrations. Second-derivative treatment of the UV spectrum makes it possible to remove the effects of the sloping baseline often encountered in spectra of highly turbid samples. The dissolution profiles obtained by FOPS were more accurate with lower and consistent %RSD as compared with the HPLC method, particularly in the case of immediate-release multiparticulates. The FOPS method was also faster and less labor intensive. Because of its various advantages, fiber-optic dissolution is fast becoming an important tool for research and development. Its ease of use, high “data density,” high data-collection speed, and hands-free monitoring make the FOPS method extremely useful as compared with the traditional methods of dissolution testing. Published: July 6, 2007     

A novel technique for the study of bacterial cell mechanical properties

A micromanipulation method is described for measuring the bursting forces of bacteria and relating them to cell size. At a compression speed of 6.2 m s^–1, bursting forces of three samples of rapidly growing Staphylococcus epidermis from a batch culture varied from 3 to 34 N with an average value of 13.8 N (standard error 0.8 N). Escherichia coli grown in continuous culture at a specific growth rate of 0.5 h^–1 had bursting forces varying from 1 to 9 N with an average value of 3.6 N (standard error 0.4 N). In squeeze-hold experiments, force relaxation was observed, which was attributed to water loss from the cells, or viscoelasticity, or both. At high compression speed, such as 6.2 m s^–1, this relaxation could be neglected. Micromanipulation strength measurements might be used in studies of cell mechanical disruption and of the dependence of cell strength on cell physiology.     

Derivative emission spectrofluorimetry: Application to the analysis of newly approved FDA combination of ibuprofen and famotidine in tablets

A new combination of ibuprofen (NSAID) and famotidine (H₂ receptor antagonist) was recently approved by the FDA. It was formulated to relief pain while decreasing the risk of ulceration, which is a common problem for patients receiving NSAID. A rapid and simple derivative emission spectrofluorimetric method is proposed for the simultaneous analysis of this combination in their pharmaceutical preparation. The method is based upon measurement of the native fluorescence intensity of the two drugs at λ_ex = 233 nm in acetonitrile. The emission data were differentiated using the first (D1) derivative technique. The plots of derivative fluorescence intensity versus concentration were rectilinear over a range of 2–35 and 0.4–8 µg/mL for both ibuprofen (IBU) and famotidine (FAM), respectively. The method was sensitive as the limits of detection were 0.51 and 0.12 µg/mL and limits of quantitation were 1.70 and 0.39 µg/mL, for IBU and FAM respectively. The proposed derivative emission spectrofluorimetric method was successfully applied for the determination of the two drugs in their synthetic mixtures and tablets with good accuracy and precision. The proposed method was validated as per ICH guidelines. Copyright © 2014 John Wiley & Sons, Ltd.     

A modified technique to obtain uniform precipitation of lanthanum tracer in the extracellular space.

A method for obtaining a uniform, dense precipitate of lanthanum nitrate to delineate extracellular space is described. Improvement of the previous technique is achieved by phosphate precipitation of lanthanum in the tissue carried out at low temperature. This method has been successfully applied to bone marrow.     

Odoriferous Therapy: A Review Identifying Essential Oils against Pathogens of the Respiratory Tract

This review explores the body of scientific information available on the antimicrobial properties of essential oils against pathogens responsible for respiratory infections and critically compares this to what is recommended in the Layman's aroma‐therapeutic literature. Essential oils are predominantly indicated for the treatment of respiratory infections caused by bacteria or viruses (total 79.0 %), the efficacy of which has not been confirmed through clinical trials. When used in combination, they are often blended for presumed holistic synergistic effects. Of the essential oils recommended, all show some degree of antioxidant activity, 50.0 % demonstrate anti‐inflammatory effects and 83.3 % of the essential oils showed antihistaminic activity. Of the essential oils reviewed, 43.8 % are considered non‐toxic while the remaining essential oils are considered slightly to moderately toxic (43.7 %) or the toxicity is unknown (12.5 %). Recommendations are made for further research into essential oil combinations.     

Improving the tablet characteristics and dissolution profile of ibuprofen by using a novel coprocessed superdisintegrant: A technical note

Summary and Conclusion  The coprocessed superdisintegrant proved to be superior to the physical blend in terms of flow due to size enlargement. Furthermore, the coprocessed superdisintegrant displayed superiority in terms of crushing strength, disintegration time, and drug dissolution. The advantages of the proposed method are easy adaptability in industry and the possibility of bypassing the existing patents in the ereas of quick disintegration and dissolution. Published: February 16, 2007     

Melt solidification technique: Incorporation of higher wax content in ibuprofen beads

The purpose of this study was to achieve incorporation of a higher amount of wax during the preparation of ibuprofen beads by a melt solidification technique for better integrity and prolonged drug release by using a combination of waxes. A mixture of cetyl alcohol (CA) and palmitic acid (PA) was used to improve the matrix integrity and drug release. The effect of variables such as CA, PA, and speed of agitation were studied using 3³ factorial design. Yield, crushing strength, and drug release were analyzed using response surface methodology. The in vitro dissolution test did not show any significant improvement in the drug release. Scanning electron microscopy (SEM) showed that beads were spherical with a smooth surface, but after dissolution became rough and porous. Differential scanning calorimetry (DSC) studies showed that different solidification and erosion properties of waxes are responsible for the inability of waxes to retard drug release even at higher concentration.     

On the synthesis of orexin A: a novel one-step procedure to obtain peptides with two intramolecular disulphide bonds.

An efficient strategy for the synthesis of orexin A, a recently discovered neuropeptide with two intramolecular disulphide bonds, was developed. Four different methods for the synthesis of peptides containing two disulphide bonds were compared and optimized with respect to reaction time, purity of the crude peptide and yield of the purified peptide. A new one-step cyclization method in solution is presented for fast, easy and high yield synthesis of orexin A, based on iodine oxidation in acetic acid/water and S-acetamidomethyl (S-Acm) and S-trityl (S-Trt) for side-chain protection of cysteine. Disulphide formation without selective side-chain protection leads to the formation of different mono- and bicyclic configurations of orexin A. These data stress the requirement of selective cysteine side-chain protection in the synthesis of orexin A.     

A novel phytoplankton chlorophyll technique: toward automated analysis

Interest in the <1 µm picoplankton fraction of naturalwaters, especially the oligotrophic oceans, has generated atrend toward the use of smaller and smaller porosity membranefilters for particulate analyses. The controversy concerningthe suitability of glass fiber versus membrane filters for retainingchlorophyll-containing parlicles is re-examined and the inadequaciesof filtration discussed. Previous comparisons in the literaturefail to resolve this controversy as tests were performed inwaters of >1.0 µm/l chlorophyll. A novel phytoplanktonchlorophyll technique for fresh and marine waters is describedwhich eliminates the need to concentrate plankton on filters.Two commercially available instruments have been modified topermit fluorescence measurements of whole water extracts. Thelower limit of detection is 0.1 µg/l in situ concentrationor 0.02 µg/l extract concentration. The technique lendsitself well to automation with particular applications to insitu fluorometry, flow cytometry and continuous chlorophylldeterminations. ^*This paper is the result of a study made at the Group for AquaticPrimary Productivity (GAP), Second International Workshop heldat the National Oceanographic Institute, Haifa, Israel in April–May1984.     

PREDICT: a method for inferring novel drug indications with application to personalized medicine

Inferring potential drug indications, for either novel or approved drugs, is a key step in drug development. Previous computational methods in this domain have focused on either drug repositioning or matching drug and disease gene expression profiles. Here, we present a novel method for the large‐scale prediction of drug indications (PREDICT) that can handle both approved drugs and novel molecules. Our method is based on the observation that similar drugs are indicated for similar diseases, and utilizes multiple drug–drug and disease–disease similarity measures for the prediction task. On cross‐validation, it obtains high specificity and sensitivity (AUC=0.9) in predicting drug indications, surpassing existing methods. We validate our predictions by their overlap with drug indications that are currently under clinical trials, and by their agreement with tissue‐specific expression information on the drug targets. We further show that disease‐specific genetic signatures can be used to accurately predict drug indications for new diseases (AUC=0.92). This lays the computational foundation for future personalized drug treatments, where gene expression signatures from individual patients would replace the disease‐specific signatures.     

A technique to obtain fibroblast cells from skin biopsies of living bats (Chiroptera) for cytogenetic studies

We developed a procedure to obtain fibroblasts from bat skin. A small fragment of the ear is removed under ether anesthesia. This material is then cut up into small pieces and cultured in standard cell culture media. Very good quality chromosome preparations for cytogenetic studies are obtained in about three weeks. Secondary cultures can be used for other biological studies. This procedure does not require sacrificing the animals.     

A novel technique to study pore-forming peptides in a natural membrane

The biophysical characteristics and the pore formation dynamics of synthetic or naturally occurring peptides forming membrane-spanning channels were investigated by using isolated photoreceptor rod outer segments (OS) recorded in whole-cell configuration. Once blocking the two OS endogenous conductances (the cGMP channels by light and the Na⁺:Ca²⁺,K⁺ exchanger by removing one of the transported ion species from both sides of the membrane, i.e. K⁺, Na⁺ or Ca²⁺), the OS membrane resistance (R _m ) was typically larger than 1 GΩ in the presence of 1 mM external Ca²⁺. Therefore, any exogenous current could be studied down to the single channel level. The peptides were applied to (and removed from) the extracellular OS side in ∼50 ms with a computer-controlled microperfusion system, in which every perfusion parameter, as the rate of solution flow, the temporal sequence of solution changes or the number of automatic, self-washing cycles were controlled by a user-friendly interface. This technique was then used to determine the biophysical properties and the pore formation dynamics of antibiotic peptaibols, as the native alamethicin mixture, the synthesized major component of the neutral fraction (F50/5) of alamethicin, and the synthetic trichogin GA IV.     

A novel technique to evaluate interactions between Saccharomyces cerevisiae cell wall and mycotoxins: application to zearalenone

Three models based on sigmoidal plotting were tested for their ability to describe zearalenone adsorption on Saccharomyces cerevisiae cell walls in vitro. All three models closely fitted the experimental data, but Hill's equation gave the most accurate parameters, and provided information on the physical and chemical mechanisms involved in the adsorption of mycotoxin on yeast cell walls.