Antitumor Activity of Some Novel 1,2,5-Thiadiazole Derivatives

Some novel thiourea,1,2,4-triazole, quinazoline, thieno[2,3-d]pyrimi-dine, and thiazolidine derivatives were synthesized to evaluate their antitumor activity. Compound (3f) is nearly as active as reference drug, (Doxorubicin) as positive control.     

Host–guest system of etodolac in native and modified β-cyclodextrins: preparation and physicochemical characterization

Etodolac, being a practically insoluble candidate, exhibits certain toxic effects and a limited bioavailability. Upon chronic use, it causes gastro-intestinal injury and increases the risk of ulcer complications. The approach of this study was to improve the physicochemical properties of the drug utilizing complexation phenomenon with β-, methyl-β- and hydroxypropyl-β-cyclodextrins, which may enhance the aqueous solubility and dissolution rate of etodolac, in an effort to increase oral bioavailability. In certain instances, this approach can be used to increase drug solubility, improve organoleptic properties and maximize the gastrointestinal tolerance by reducing drug irritation after oral administration. Differential UV measurements as well as continuous variation plots revealed the formation of equimolar complex with hydroxypropyl-β-cyclodextrin and 1:2 complexes with β-cyclodextrin and its methyl derivative. Differential scanning calorimetry (DSC), X-ray and FT-IR measurements were applied to prove inclusion complex formation and characterize the complexes. These results lend support to the idea that solubilization of etodolac is mainly related to inclusion complex formation and to a lesser extent to cyclodextrin aggregates. Understanding the factors that influence the performance of etodolac, will allow us to state that molecular encapsulation of the drug and other modifications with appropriate hydroxylation or methylation of parent β-cyclodextrin is able to overcome its problems and facilitate safe and efficient delivery of the drug.     

Dual-channel spectral subtraction algorithms based speech enhancement dedicated to a bilateral cochlear implant

In this paper, two speech enhancement algorithms (SEAs) based on spectral subtraction (SS) principle have been evaluated for bilateral cochlear implant (BCI) users. Specifically, dual-channel noise power spectral estimation algorithm using power spectral densities (PSD) and cross power spectral density (CPSD) of the observed signals was studied. The enhanced speech signals were obtained using either Dual Channel Non Linear Spectral Subtraction ‘DC-NLSS’ or Dual-Channel Multi-Band Spectral Subtraction ‘DC-MBSS’ algorithms. For performance evaluation, some objective speech assessment tests relying on Perceptual Evaluation of Speech Quality (PESQ) score and speech Itakura-Saito (IS) distortion measurement were performed to fix the optimal number of frequency band needed in DC-MBSS algorithm. In order to evaluate the speech intelligibility, subjective listening tests were assessed with 50 normal hearing listeners using a specific BCI simulator and with three deafened BCI patients. Experimental results, obtained using French Lafon database corrupted by an additive babble noise at different Signal-to-Noise Ratios (SNR), showed that DC-MBSS algorithm improves speech understanding better than DC-NLSS algorithm for single and multiple interfering noise sources.     

CoSm(SeO3)2Cl,CuGd(SeO3)2Cl,MnSm(SeO3)2Cl,CuGd2(SeO3)4 und CuSm2(SeO3)4: Übergangsmetallhaltige Selenite von Samarium und Gadolinum

CoSm(SeO₃)₂Cl, CuGd(SeO₃)₂Cl, MnSm(SeO₃)₂Cl, CuGd₂(SeO₃)₄ and CuSm₂(SeO₃)₄: Transition Metal containing Selenites of Samarium and Gadolinum The reaction of CoCl₂, Sm₂O₃, and SeO₂ in evacuated silica ampoules lead to blue single crystals of CoSm(SeO₃)₂Cl (triclinic, , Z = 4, a = 712.3(1), b = 889.5(2), c = 1216.2(2) pm, α = 72.25(1)°, β = 71.27(1)°, γ = 72.08(1)°, R_all = 0.0586). If MnCl₂ is used in the reaction light pink single crystals of MnSm(SeO₃)₂Cl (triclinic, , Z = 2, a = 700.8(2), b = 724.1(2), c = 803.4(2) pm, α = 86.90(3)°, β = 71.57(3)°, γ = 64.33(3)°, R_all = 0.0875) are obtained. Green single crystals of CuGd₂(SeO₃)₂Cl (triclinic, , Z = 4, a = 704.3(4), b = 909.6(4), c = 1201.0(7) pm, α = 70.84(4)°, β = 73.01(4)°, γ = 70.69(4)°, R_all = 0.0450) form analogously in the reaction of CuCl₂ and Gd₂O₃ with SeO₂. CoSm(SeO₃)₂Cl contains [CoO₄Cl₂] octahedra, which are connected via one edge and one vertex to infinite chains. The Mn²⁺ ions in MnSm(SeO₃)₂Cl are also octahedrally coordinated by four oxygen and two chlorine ligands. The linkage of the polyhedra to chains occurs exclusively via edges. Both, the cobalt and the manganese compound show the Sm³⁺ ions in eight and ninefold coordination of oxygen atoms and chloride ions. In CuGd(SeO₃)₂Cl the Cu²⁺ ions are coordinated by three oxygen atoms and one Cl^— ion in a distorted square planar manner. One further Cl^— and one further oxygen ligand complete the [CuO₃Cl] units yielding significantly elongated octahedra. The latter are again connected to chains via two common edges. For the Gd³⁺ ions coordination numbers of ?8 + 1”? and nine were found. Single crystals of the deep blue selenites CuM₂(SeO₃)₄ (M = Sm/Gd, monoclinic, P2₁/c, a = 1050.4(3)/1051.0(2), b = 696.6(2)/693.5(1), c = 822.5(2)/818.5(2) pm, β = 110.48(2)°/110.53(2)°, R_all = 0.0341/0.0531) can be obtained from reactions of the oxides Sm₂O₃ and Gd₂O₃, respectively, with CuO and SeO₂. The crystal structure contains square planar [CuO₄] groups and irregular [MO₉] polyhedra.     

Formulation of Risperidone as Self-Nanoemulsifying Drug Delivery System in Form of Effervescent Tablets

Risperidone is an atypical antipsychotic drug used to treat schizophrenia. This study aims to formulate risperidone as effervescent tablets to improve patient compliance. Different nanoemulsion combinations were loaded with risperidone to improve its poor water solubility then adsorbed on Aeroperl. The formula showing highest drug dissolution was formulated as effervescent tablets. Factorial design was applied for different tablet formulation variables and the prepared formulae were tested for different criteria in comparison with their corresponding formulae containing drug without nanoemulsion formulation. Statistical analysis was used to determine the most desirable tablet formula considering its Carr index, effervescence time, and drug release.     

Kinetic Study on the Isomerization of Perindopril by HPLC

The isomerization of perindopril has been investigated using dynamics chromatography and an unified equation introduced by Trapp that was based on stochastic and theoretical plate models to determine the energies. The isomerization rate constants and Gibbs activation energies of isomerization are directly calculated from chromatographic peak parameters, i.e., retention times of the inter-converting species, peak width at half height, and relative plateau height. From the rate constant \( k_{1}^{ue} (T) \), measured at variable temperatures, the kinetic eyring activation parameters ΔG ^#, ΔH ^# and ΔS ^# of isomerization of perindopril were obtained. By variation of the flow rate of the mobile phase, the expected independence of the isomerization barrier from the chromatographic time scale was demonstrated for the first time. The relationships between peak shape and chromatographic conditions, such as flow rate, temperature, pH, organic modifier, and β-cyclodextrin, such as an additive, were investigated. In addition, an NMR investigation on perindopril was described.

     

In Vitro Biomineralization and Bulk Characterization of Chitosan/Hydroxyapatite Composite Microparticles Prepared by Emulsification Cross-Linking Method: Orthopedic Use

Chitosan/hydroxyapatite composite microparticles were prepared by a solid-in-water-in-oil emulsification cross-linking method. The characteristics and activity in presence of simulated body fluid for 14 and 21?days were investigated. The size distribution, surface morphology, and microstructure of these biomaterials were evaluated. The scanning electron microscopy revealed an aggregate of microparticles with a particle size, ranged from 4 to 10???m. The deposited calcium phosphate was studied using X-ray diffraction analysis, Fourier transform infrared spectroscopy, and inductively coupled plasma/atomic emission?spectroscopy analysis of phosphorus. These results show that the mineral, formed on microparticles, was a mixture of carbonated hydroxyapatite and calcite. Scanning electron microscopy revealed that calcium phosphate crystals growth was in form of rods organized as concentric triangular packets interconnected to each other by junctions. Interaction between chitosan and growing carbonated hydroxyapatite and calcite crystals are responsible for a composite growth into triangular and spherical shapes. The results demonstrated that these microparticles were potential materials for bone repair.     

Chitosan/cyclodextrin nanoparticles as drug delivery system

One of the most attractive areas of research in drug delivery is the design of nanomedicines consisting of nanosystems that are able to deliver drugs to the right place, at appropriate time. Natural polysaccharides, due to their outstanding merits, have received more and more attention in the field of drug delivery systems. In particular, polysaccharides seem to be the most promising materials in the preparation of nanometric carriers. The main goal of the present study was to investigate the potential of a recent generation of hybrid polysaccharide nanocarriers, composed of chitosan (CS) and an anionic cyclodextrin, carboxymethyl-β-cyclodextrin (CM-β-CD), for the encapsulation of a model drug, sulindac. CS and CM-β-CD were processed to nanoparticles (NPs) via the ionotropic gelation technique. The stoichiometric ratio between these two polymers was found to influence particle size and zeta potential. Decreasing CS:CM-β-CD ratio led to an increase in particle size and decrease in zeta potential. DSC and FTIR analyses confirmed formation of NPs and encapsulation of sulindac inside them. Release profiles indicate a continuous release of the drug throughout 24?h. However, the rate of release was more rapid during the first hours; about 55–90% of the drug being released after 3?h.