The stereochemistry of 4,8-dimethyl-6-phenyl-5,6,7,8-tetrahydro-4H-1,3,6-dioxazocin-2-ones using NMR

Two isomeric 4,8-dimethyl-6-phenyl-5,6,7,8-tetrahydro-4H-1,3,6-dioxazocin-2-ones were prepared, and their pmr and cmr spectra were examined. From the tris(dipivaloylmethanato) europium (Eu(dpm)₃) shift reagent and the dihedral angle, the title compounds are found to exist in the eq-ax and eq-eq methyl groups with boat-chair form.     

Quantitative determination of amorphous nicardipine hydrochloride in long acting formula (NIC-LA) using light anhydrous silicic acid

We investigated a method to quantitatively determine amorphous nicardipine hydrochloride (NIC) in the NIC-long acting formula (LA) model formulas prepared using NIC, light anhydrous silicic acid (LASA) and carboxymethylethylcellulose (CMEC). Consequently, since the quantity of total NIC in the formula can be determined by means of HPLC and crystal NIC can be determined by the differential scanning calorimetry (DSC) method because the heat of fusion (85.08 J/g) of NIC is constant and unaffected by excipients, we developed the HPLC-DSC method by which the quantity of amorphous NIC is calculated as the difference between the quantity of total NIC determined by HPLC and the quantity of crystal NIC determined by DSC. This practical HPLC-DSC method was confirmed to have good accuracy and reproducibility.     

Time resolved fluorescent analysis for sealed heating of dimethyl-β-cyclodextrin and naphthalene system

The inclusion process of naphthalene into heptakis-(2,6-di-O-methyl)--cyclodextrin (DMCD) during the sealed heating was investigated by using solid state time,resolved fluorescent analysis. Fluorescence lifetimes of naphthalene in naphthalene crystals and in inclusion complex with DMCD prepared by coprecipitation were determined 59 ns and 88 ns, respectively. Fluorescence lifetime of naphthalene monomer becomes longer after inclusion complex formation. Fluorescence lifetimes of naphthalene monomer and excimer in the sealed heating complex were determined about 80 ns and 100 ns, respectively. By setting the observing wavelength of time resolved fluorescent analysis at 355 nm, the formation and the decay of the excimer state of naphthalene during the sealed heating process were successfully confirmed.     

Reduction of poly(4-vinylpyridine)-coordinated ferriprotoporphyrin IX by N-benzyl-1,4-dihydronicotinamide in N,N-dimethylformamide

The reduction of a ferriprotoporphyrin IX–pyridine or poly(4-vinylpyridine) complex by N-benzyl-1,4-dihydronicotinamide in N,N-dimethylformamide to yield a corresponding ferro complex was studied kinetically and thermodynamically by spectral measurements. The reduction was confirmed to proceed via the intermediate. The rate of the reduction of the ferric iron was faster in the poly(4-vinylpyridine) complex than in the pyridine complex. This was caused by the adsorption of the reductant to the polymer ligand, causing the increase in the frequency factor of the reaction.     

Factors affecting the formation in the solid state of the metastable complex between naphthalene and dimethyl-β-cyclodextrin

An equimolar mixture of naphthalene and amorphous heptakis-(2,6-di-O-methyl)--cyclodextrin (DMCD) was heated at 70 or 90°C in a sealed container. After heating ffor 15 min at 90°C, the mixture was crystallized to show an excimer fluorescence of naphthalene, and the fluorescence spectrum changed to a monomer emission by further prolongation of heating time, accompanied by a slight change in its powder X-ray diffractogram. It is suggested that a metastable complex showing the excimer emission of naphthalene was transformed to a stable complex showing the monomer emission. The mixing molar ratio of naphthalene to DMCD was also found to affect the transformation temperature of the complex.     

Electrochemically induced aggregation of intra-particle cationic nanogel complexes with a stoichiometric amount of bound polyanions

The present study aimed to see the effect of an applied electric field on the stability of a colloid system in which overall electroneutrality is maintained in a metastable state. We employed two polyelectrolyte nanogels (PENG) based on N,N′-methylenebisacrylamide (MBA)-cross-linked terpolymer composed of N-isopropylacrylamide (NIPA), acrylic acid (AAc) and 1-vinylimidazole (VI) and MBA-cross-linked copolymer of NIPA and VI. The complexes of these PENG particles with potassium poly(vinyl alcohol) sulfate (KPVS) were formed in an aqueous HCl solution (1 mM, pH 3) which allows a complete ionization of the PENG-fixed imidazole groups. The amount of KPVS anions was adjusted so as to become equivalent to that of PENG-fixed cations. The complex dispersion was electrolyzed in a simple cell made of a glass tube. A fine platinum wire was used as an electrode for both cathode and anode. It was suggested that the electrochemically induced increase in pH in the cathodic side causes the aggregation of the complex particles due to a partial dissociation of the bound polyanions from the complex.     

Central Limit Theorems for Open Quantum Random Walks on the Crystal Lattices

We consider the open quantum random walks on the crystal lattices and investigate the central limit theorems for the walks. On the integer lattices the open quantum random walks satisfy the central limit theorems as was shown by Attal et al (Ann Henri Poincaré 16(1):15–43, 2015). In this paper we prove the central limit theorems for the open quantum random walks on the crystal lattices. We then provide with some examples for the Hexagonal lattices. We also develop the Fourier analysis on the crystal lattices. This leads to construct the so called dual processes for the open quantum random walks. It amounts to get Fourier transform of the probability densities, and it is very useful when we compute the characteristic functions of the walks. In this paper we construct the dual processes for the open quantum random walks on the crystal lattices providing with some examples.

     

Effect of grinding on the dehydration behavior of nedocromil sodium hydrates

Nedocromil sodium has a number of known hydrate states, a monohydrate, a trihydrate and a heptahemihydrate, including an amorphous state. Effect of grinding on the hydration states of nedocromil sodium crystals was studied. After grinding the trihydrate, heptahemihydrate was observed in the ground sample, even though, the water content in the ground sample was not sufficient to cover the heptahemihydrate’s hydration level. On the other hand, in the ground heptahemihydrate, trihydrate was existed. Apparent activation energies (ΔE) for hydrates, monohydrate→anhydrate, trihydrate→monohydrate and heptahemihydrate→amorphous(anhydrate), were calculated using TG data. ΔE for the dehydration of heptahemihydrate was significantly lower than that of other hydrates. Obtained ΔE data explained the inter-conversion behavior of nedocromil sodium induced by grinding.     

Component Crystallization and Physical Collapse during Freeze-Drying of L-Arginine-Citric Acid Mixtures

Component crystallization and physical collapse during freeze-drying of aqueous solutions containing protein-stabilizing L-arginine and citric acid mixtures were studied. Freeze-drying microscopy (FDM) and thermal analysis of the solute-mixture frozen solutions showed collapse onset at temperatures (T(c)) approximately 10°C higher than their T(g)'s (glass transition temperatures of the maximally freeze-concentrated solute phase). Experimental freeze-drying of these solutions at a low chamber pressure showed the occurrence of physical collapse at shelf temperatures close to or slightly higher than the T(c). Slower ice sublimation at higher chamber pressures induced the physical collapse from lower shelf temperatures. The large effect of chamber pressures on the collapse-inducing shelf temperatures confirmed significance of the sublimation-related heat loss on the sublimation interface temperature during the primary drying. Drying of the single-solute L-arginine solution resulted in cake-structure solids composed of its anhydrous crystal. Thermal and powder X-ray diffraction (PXRD) analysis suggested slow crystal nucleation of L-arginine dihydrate in the frozen solutions. Characterization of the frozen solutions and freeze-dried solids should enable rational formulation design and process control of amino acid-containing lyophilized pharmaceuticals.