Pharmaceutica acta Helvetiae最新文献

Usually, chemical or technological operations are used to mask the taste of unpleasant-tasting drugs. To reduce the development cost of such drugs, we propose a new approach which does not require the modification of the existing formulation nor the use of additional costly technological operations. Different particle size fractions of two unpleasant-tasting drugs (niflumic acid and ibuprofen) were blended in binary mixes with different particle size fractions of two non-tasting excipients (ethyl cellulose and hydroxypropyl methylcellulose). By selecting the appropriate mixes of identical composition but different organisations, as predicted from surface energy data, it was possible to use the different organisations to modify the taste of the mixes for a panel of 10 healthy volunteers.

Isatin (Indole 2,3-dione), its 5-chloro and 5-bromo derivatives were added to 3-amino-2-methylmercapto quinazolin-4(3H)-one to form Schiff bases and the N-Mannich bases of these compounds were synthesized by reacting with formaldehyde and several secondary amines. Their chemical structures have been confirmed by means of their IR, ${}^1\text{H}$-NMR data and by elemental analysis. Investigation of antimicrobial activity of compounds was done by an agar dilution method against 26 pathogenic bacteria, 8 pathogenic fungi and anti-HIV activity against replication of HIV-1 (III B) in MT-4 cells. Among the compounds tested 5-chloro-3-(3′,4′-dihydro-2′-methylmercapto-4′-oxoquinazolin-3′-yl)-1-morpholino methyl imino isatin was the most active antimicrobial agent.

Controlled release sodium alginate (Na–Alg) beads containing diclofenac sodium (DS) have been prepared by precipitation of Na–Alg in alcohol followed by crosslinking with glutaraldehyde (GA) in acidic medium. Preparation of the beads was optimized by considering the percentage entrapment efficiency, swelling capacity of beads in water and their release data. The percentage entrapment efficiency was found to vary between 30 and 71 depending upon the conditions of their preparations. The beads produced at higher temperatures and longer times of exposure to the crosslinking agent have shown the lower entrapment efficiency, but extended release of DS from the beads. The scanning electron microscopic studies indicated nonporous smooth surfaces and the differential scanning calorimetric data indicated the molecular level dispersion of the drugs in the beads.

The present investigation reports a new family of lipid nanoparticles biomimetic of lipoproteins, lipoprotein-mimicking biovectorized systems (LMBVs), for the delivery of methotrexate. LMBVs were prepared by microemulsion congealing technique, and the composition and process were optimized. The palmitoylpolyethylene glycol 4000 (p-PEG 4000) was anchored on LMBVs as apoprotein analogue. Various formulations were prepared and characterized for size and polydispersity, zeta potential, drug entrapment efficiency, anchoring efficiency, release kinetics, pharmacokinetics and tissue distribution. The size was 70–76 nm and the polydispersity was 0.09–0.18. The zeta potential was −63.2 which was reduced to −19.3 after p-PEG 4000 coating. Entrapment efficiency varied from 22.6% to 30.2%. Anchoring efficiency was 74.0±3.9%. The drug release showed zero-order profile. Their circulation half-life was enhanced and exhibited capability to accumulate in tissues for longer periods. The composition of lipidic part of LMBVs and p-PEG 4000 anchoring impart similarity with natural lipoproteins in terms of in vivo behaviour. This new drug carrier named LMBVs, holds promise for targeting and systemic controlled release, which may prove effective in the treatment of various types of cancer.

Two types of fat emulsions inlets are marketed with Baxa MM23® automated compounder. This system is used in Robert Debré hospital pharmacy unit for the daily preparation of parenteral binary solutions. The aim of this study was to compare these inlets for the compounding of all-in-one admixtures. Baxa inlet was chosen instead of Cair inlet because it is more accurate although it is more expensive.

The purpose of this study was to elucidate the influence of ternary mixtures of different emulsifiers on the physicochemical properties of lipid emulsions by the aid of simplex lattice design with constraints. The physicochemical properties and the stability during the autoclaving process, as a consequent result, were investigated by examining the changes in particle size, zeta potential, and cloud point. The emulsifiers chosen were lecithin, Synperonic F68 and Tween 80. In addition, their potential for hemolysis was evaluated as it may serve as an in vitro toxicity screening method. The formulations with only Tween 80 as an emulsifier showed a noticeable change in the particle size during autoclaving as well as a remarkable erythrocyte membrane damage. In contrast, phospholipids and Synperonic F68 formulations displayed good stability during autoclaving and showed almost no hemolytic activity. Moreover, mixing Tween 80 with either lecithin or Synperonic F68 improved the stability of these formulations during the autoclaving process. Simultaneously, this led to a remarkable decrease in the hemolytic effect. This observation could be partially correlated with the cloud point, which increased by adding lecithin and was less influenced by adding Synperonic F68. This in turn resulted in an increase in the surface charge, when lecithin was added. This results in a higher resistance of the emulsifier complex to dehydration producing a more stable emulsifier film around the oil droplets. These factors inhibited the flocculation of the emulsifiers and could hinder the coalescence of the oil droplets during the autoclaving process.

Peptides and polypeptides play a critical role in the immune system and are therefore predestined as a source for new approaches in immunotherapy. For example, antigenic peptides which can trigger a specific immunological response have been successfully used for vaccination. In contrast, cytokines have to be considered as rather non-specific immunomodulators. In addition, certain peptides with unknown mode of action have shown promising immunomodulating properties. An example is the pentapeptide thymopentin (TP5), which represents the active sequence of the originally described thymopoietin (TP). TP was recently identified as a fragment of the thymopoietins (TMPOs), a family of nuclear proteins. In vitro assays showed that TP5 affects the function of T cells and monocytes measured by enhanced cGMP level and the triggering of cellular signalling, respectively. In vivo studies demonstrated the capability of TP5 to improve an imbalanced immune system. TP5 exhibited important clinical features and further investigations on its mode of action are necessary to rationally create TP5 peptide analogs or peptidomimetics.