Formulation study for lansoprazole fast-disintegrating tablet. II. Effect of triethyl citrate on the quality of the products

The purpose of this study was to develop enteric-coated microgranules for the lansoprazole fast-disintegrating tablet (LFDT), which is a rapidly disintegrating tablet containing enteric-coated microgranules. In our previous study, it was clarified that sufficient flexibility of the enteric layer was achieved by the optimized combined ratio of methacrylic acid copolymer dispersion to ethyl acrylate-methyl methacrylate copolymer dispersion and adding the optimized concentration of triethyl citrate to reduce the damage during the compression process. However, since triethyl citrate has an unpleasant bitter taste and is especially incompatible with lansoprazole, it adversely affects the taste and stability of lansoprazole in the enteric-coated microgranules. The enteric layer containing macrogol 6000 was proven useful to improve the unpleasant bitter taste and stability of lansoprazole, because macrogol 6000 does not have an unpleasant bitter taste and is more compatible than triethyl citerate. By covering the inner (first enteric layer) and outer side (third enteric layer) of the enteric layer containing triethyl citrate (second enteric layer) with the enteric layer containing macrogol 6000, we resolved the stability problem of lansoprazole and the unpleasant bitter taste. Finally, we developed enteric-coated microgranules comprising seven layers: 1) core, 2) active compound layer, 3) intermediate layer, 4) first enteric layer, 5) second enteric layer, 6) third enteric layer, and 7) over coating layer. The enteric-coated microgranules have the multiple functions of reducing the damage to the enteric layer during the compression process, improving the stability of lansoprazole, and masking the unpleasant bitter taste.     

Preferential hydration and the exclusion of cosolvents from protein surfaces

Protein stability is enhanced by the addition of osmolytes, such as sugars and polyols and inert crowders, such as polyethylene glycols. This stability enhancement has been quantified by the preferential hydration parameter which can be determined by experiments. To understand the mechanism of protein stability enhancement, we present a statistical mechanical analysis of the preferential hydration parameter based upon Kirkwood-Buff theory. Previously, the preferential hydration parameter was interpreted in terms of the number of hydration waters, as well as the cosolvent exclusion volume. It was not clear how accurate these interpretations were, nor what the relationship is between the two. By using the Kirkwood-Buff theory and experimental data, we conclude that the contribution from the cosolvent exclusion dominantly determines the preferential hydration parameters for crowders. For osmolytes, although the cosolvent exclusion largely determines the preferential hydration parameters, the contribution from hydration may not be negligible.     

Monte Carlo simulation of spatial distribution of X rays in multifilm targets. III: optimum design as applied to W/Al‐film targets

The brightness of the X‐ray source in a W/Al‐film target used for X‐ray projection microscopy was studied by an approach using the Monte Carlo simulation. Since continuous X rays generated in a thin film have a specific angular distribution of emission, the brightness of the continuous X‐ray source cannot simply be estimated on the assumption that the angular distribution is homogeneous. The newly developed approach using the Monte Carlo simulation enables the evaluation of the effective source size, angular distribution, and brightness of a continuous X‐ray source with sufficient accuracy that it leads to the optimum design of a high‐brightness X‐ray source for uses such as X‐ray projection microscopy. The Monte Carlo calculations were performed for W(Δz)/Al (200 µm)‐film targets with different thicknesses of W film, Δz, under bombardment of 60 kV electrons. The results have suggested an optimum design consisting of a W (2 µm)/Al (200 µm)‐film target as most promising for providing an X‐ray source of higher brightness than the W (5 µm)/Al (200 µm)‐film target, which has already been in practice for X‐ray projection microscopy. Copyright © 2006 John Wiley & Sons, Ltd.     

Metal-ion-assisted hydrolysis of dipeptides involving a serine residue in a neutral aqueous solution

Dipeptides having a serine residue at the C-terminus, X-Ser, where X is an appropriate amino acid residue, were efficiently hydrolyzed in the presence of ZnCl2 at pH 7.0. The rapid hydrolysis of X-Ser is due to an autocatalysis of the hydroxy group in the serine residue, and is found to be accelerated by a metal ion, in particular by ZnCl2. Roles of the metal ion in the hydrolysis of peptides involving a serine residue, in relation to the recently reported protein cleavages, are discussed.     

13C- and 1H-NMR and FTIR spectroscopic evidence for aggregate formation of organosilanes in toluene

 Changes in the ¹³C and ¹H NMR chemical shifts of the silane coupling agent (3-aminopropyltri-ethoxysilane, APTS) in toluene, which were detected as the concentration of APTS increased, have been interpreted in terms of the formation of micelles and the presence of a critical micelle concentration (CMC) equal to ca. 0.47 mol 1^-1. For the protons of the n-propyl segment, ¹H NMR splitting patterns have been analyzed and conformations of the propyl segment have been discussed. Plots of relative absorbance of the two NH₂ stretch IR bands at 3324 and 3384 cm^-1 against concentration provided an inflection point (corresponding to the CMC) at a value equal to 0.46 mol 1^-1. Thus, consideration of the interaction of APTS with a surface must take into account the presence of both APTS aggregates as well as APTS monomers. Received: 16 August 1996 Accepted: 26 September 1996     

Palladium-catalyzed preparation of α-allyl esters and α,β-unsaturated esters from saturated esters via their silyl acetals

Reaction of ketene silyl acetals with allylic carbonates in the presence of palladium-phosphine catalyst in dioxane gives α-allyl esters in high yields. When the reaction is carried out with phosphine-free palladium catalyst in nitriles, α,β-unsaturated esters are obtained in good yields.     

Dynamic coordination polymers with 4,4'-oxybis(benzoate): reversible transformations of nano- and nonporous coordination frameworks responding to present solvents

Reversible construction of a nanoporous framework from a nonporous framework has been found in the zinc(II) coordination polymer with 4,4'-oxybis(benzoate) (oba). [Zn(2)(oba)(2)(dmf)(2)].2DMF (1), which has 1 nm scale channels, transforms to the nonporous coordination polymer [Zn(oba)(H(2)O)] (2) with the loss of the open framework. Compound 2 on treatment with DMF reversibly yields nanoporous compound 1.     

Biological activities of chemically synthesized derivatives of lipid A: tetraacetyl-monosaccharides linked to 2,3-acyloxyacylglucosamine-4-phosphate

The mitogenicity and lethal toxicity of chemically synthesized lipid A analogs, in which 2,3-acyloxyacylglucosamine-4-phosphate (acyl-GlcN-4P) is linked to a tetraacetyl (Ac4)-monosaccharide, i.e., Ac4-glucose (A-211), Ac4-mannose (A-212), Ac4-galactose (A-213) or Ac4-glucosamine (A-214), were compared with those of tetraacetyl-3-deoxy-D-manno-2-octulosonic acid (Ac4-KDO) linked to acyl-GlcN-4P (A-203). All the compounds were capable of increasing incorporation of 3H-thymidine into splenocytes of C57BL/6 mice at doses of 50 and 100 micrograms/ml, but the mitogenic activity of A-203 at these doses seems to be stronger than those of the analogs. Intravenous injection of A-203, A-211, and A-213 did not exhibit lethal toxicity even at a high dose (50 micrograms/mouse) in C57BL/6 mice loaded with D-galactosamine hydrochloride. However, A-212 and A-214 showed lethality at the doses of 10 and 50 micrograms/mouse, respectively. The findings indicate that the biological activity of these compounds is affected by the kind of monosaccharide linked to acyl-GlcN-4P.