Pre-formulation of an oral cyclosporine free of surfactant

The purpose of this study was to develop a new oral cyclosporine A (CsA) formulation free of surfactant cremophor using cyclodextrin terpolymers (P-αβ-CD, P-βγ-CD and P-αγ-CD) as excipients in attempt to enhance its stability, dissolution rate and eliminate surfactant side effects. Two spray-dried dispersions (SDDs) containing poorly water-soluble CsA were prepared with either P-αβ-CD, P-βγ-CD or P-αγ-CD using water ( $ F_{{{\text{H}}_{2} {\text{O}}}} $ ) and ethanol (F _EOH) via spray-drying technique and characterized by scanning electron microscopy, powder X-ray diffraction, particle size distribution, circular dichroism (CD) and nuclear magnetic resonance along with the dissolution study which was compared to Neoral^® and Sandimmune^®. The results showed an interaction between CsA and P-αβ-CD, P-βγ-CD and P-αγ-CD without secondary structure change of CsA. The order of the CsA release from the terpolymers was ranked as follows: P-αγ-CD/CsA ( $ F_{{{\text{H}}_{2} {\text{O}}}} $ ) = Neoral^® > P-βγ-CD/CsA ( $ F_{{{\text{H}}_{2} {\text{O}}}} $ ) > P-αβ-CD/CsA ( $ F_{{{\text{H}}_{2} {\text{O}}}} $ ) > P-αγ-CD/CsA (F _EOH) > Sandimmune^® > P-αβ-CD/CsA (F _EOH) > P-βγ-CD/CsA (F _EOH). The results of ( $ F_{{{\text{H}}_{2} {\text{O}}}} $ ) could be explained by hydrophilisation and absence of crystallinity of CsA while maintaining part of its crystallinity in the case of formulations (F _EOH). In summary, developed SDD formulations P-αγ-CD/CsA ( $ F_{{{\text{H}}_{2} {\text{O}}}} $ ) revealed same dissolution profile as Neoral^® and better than Sandimmune^®. These systems seem to be stable to carry cyclosporine and release it, while preserving structure and thus, potentially, also maintaining cyclosporine activity.     

On the distributivity of the lattice of solvable totally local fitting classes

It is proved that the lattice of all solvable totally local Fitting classes is algebraic and distributive. Translated fromMatematicheskie Zametki, Vol. 67, No. 5, pp. 662–673, May, 2000.     

Effect of partially methylated β cyclodextrin on percutaneous absorption of metopimazine

Metopimazine (MPZ) is an antiemetic drug used by oral and rectal administration. A transdermal delivery system of MPZ may present a great advantage for the treatment of nausea and vomiting to improve therapeutic adhesion. MPZ is a lipophilic drug with poor water solubility. Partially methyled β cyclodextrin (PMβ-CD) was tested to enhance percutaneous absorption of MPZ. Complex MPZ/cyclodextrin was characterized by Higushi’s phase solubility, Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analyses and MPZ octanol partition coefficient was also determinated. The permeation of free MPZ and inclusion complex through pig skin were investigated using Franz’s cells. Four concentrations of cyclodextrins, 0, 5, 10 and 20% were tested. Partition coefficient was depending on pH of the solution. At pH 5.5, MPZ ionization increased the hydrophily (0.71) and at pH 10.3, non-ionized MPZ was the dominant form (591). The solubility of MPZ increased with the concentration of PMβ-CD and the phase solubility diagram is an Ap type. The used characterization analyses demonstrated the formation of an inclusion complex and this complex improved percutaneous absorption of MPZ. No MPZ flux was detected for a suspension of MPZ and it was more important with MPZ hydrochloride, 0.177 ± 0.044 μg/h/cm2. Flux was increased to 0.570 ± 0.058 μg/h/cm2 with a concentration of 20%. The use of cyclodextrin with MPZ hydrochloride increased also the percutaneous absorption with 0.549 ± 0.175 μg/h/cm2 for a concentration of 5%, 0.435 ± 0.031 μg/h/cm2 for a concentration of 10% and 0.474 ± 0.054 μg/h/cm2 for a concentration of 20%. This study shows that PMβ-CD improves percutaneous penetration of MPZ. But the absorption is not enough to allow a therapeutic effect. Cyclodextrin complex increases MPZ solubility and this bioavailability at the skin surface, and cyclodextrin may also modify the barrier propriety of skin.     

On splitting‐based mass and total energy conserving arbitrary order shallow‐water schemes

A new method for numerical solution to the shallow‐water equations is suggested. The method allows constructing a family of finite difference schemes of different approximation order that conserve the mass and the total energy. Our approach is based on the method of splitting, and unlike others it permits to derive conservative numerical schemes after discretizing all the partial derivatives, both spatial and temporal. The schemes thus appear to be fully discrete, both in time and in space. Besides, due to a simple structure of the matrices appeared therewith, the method provides essential benefits in the computational cost of solution and is easy‐to‐implement in the Cartesian and spherical geometries. Numerical results confirm functionality and efficiency of the developed method. © 2006 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 2007     

Nimesulide/cyclodextrin/PEG 6000 ternary complexes: physico-chemical characterization, dissolution studies and bioavailability in rats

Purpose Ternary solid dispersions were prepared in order to estimate the effect of a double hydrophilization by cyclodextrins and PEG 6000 on nimesulide apparent characteristics. Ternary solid dispersions of nimesulide, cyclodextrins and PEG 6000 were characterized using DSC, FT-IR, dissolution studies and evaluating the bioavailability in rats. Methods Ternary solid dispersions were prepared either using native powders or using a preformed inclusion complex of nimesulide and cyclodextrin. Inclusion complexes and pure drug were used as references. Circulating nimesulide was measured out in rat plasma after orally administration of our different products (ternary solid dispersions, inclusion complexes and pure drug). Results An improvement of the nimesulide dissolution rate was obtained with inclusion complexes and ternary solid dispersion. In rat plasma, inclusion complexes and ternary solid dispersion improved T _max. Conclusions A second hydrophilization of inclusion complexes by PEG 6000 does not allow to achieve better results concerning nimesulide concentration in rat plasma or in dissolution studies than with inclusion complexes alone.     

Cyclicity conditions for <Emphasis Type="Italic">G</Emphasis>-chief factors of normal subgroups of a group <Emphasis Type="Italic">G</Emphasis>

We find conditions under which every G-chief factor of a normal subgroup E of a finite group G is cyclic.     

Synthesis of per-substituted hydrophilic and hydrophobic ��-cyclodextrin derivatives

The aim of this work was to synthesize new cyclodextrin derivatives from native ??-cyclodextrin by allylation reactions and indium metal in aqueous and organic medium. The resulted products could be used to prepare a new hydrophilic pharmaceutical active ingredient. A hydrophobic derivative can also be prepared by the same method. Indeed, the allylation reactions allow the creation of a stereogenic centers and the introduction of an allyl group lead to development of various functionalization of CD sites. Natural ??-cyclodextrin was treated with allyl bromide and sodium hydride in dimethylformamide (DMF) at room temperature, which resulted in the formation of O-perallylated ??-cyclodextrin A₁ (98%). Through successive reactions of oxidation, reduction and allylation, the latter was converted into per 2, 3, 6-tri-O-(2-hydroxypent-4-enyl) ??-cyclodextrins A₄ (40%). Others derivates of CD type B₃ and C₃ were synthesized by series of reaction to give multifunctionalized cyclodextrins with yield of 25 and 30%, respectively.     

Finite Groups with Weakly Subnormal and Partially Subnormal Subgroups

Siberian Mathematical Journal - We study the influence of weakly subnormal and partially subnormal subgroups on the structure of a&nbsp;group&nbsp; $ G $ . In particular, we prove that a...     

On one generalization of modular subgroups

We study the influence of generalized modular subgroups on the structure of finite groups.