Minodronic acid, a new bisphosphonate, is susceptible to low levels of aluminum ions leaching from regular glass ampoules when in solution. This could lead to an increase in microscopic particles depending on the containers, formulations or storage conditions used. In this study, the compatibilities of three chemically-treated glass ampoules for minodronic acid solution were examined. The formulation that demonstrated a sudden particulate increase in regular glass ampoules after storage for 5 mo at 25°C was used as a test solution. The particulate generation in each ampoule was evaluated by a newly introduced stress test (4 freeze-thaw cycles after storage for 4 wk at 80°C) and a regular long-term test (storage for 6 mo at 25°C). The long-term test revealed that sulfur-treated ampoules and nitric acid-treated ampoules did not show the particulate increase even though silicone-treated ampoules did. In contrast, the stress test, which was designed to quickly choose robust formulations in regular glass ampoules, was inappropriate for choosing suitable ampoules because the results of the stress test did not correlate well with those of the long-term test due to the intense stress placed on the ampoules. SiO₂-treated ampoules, which suppressed the particulate increase at 25°C, also generated an excess amount of particles after the stress test. It appears that the protective SiO₂ layer was severely damaged due to the harsh temperature conditions.

This study examined the transfection activity and cytotoxicity of the synthetic polycationic peptides, poly (L-lysine), poly (L-ornithine), poly (L-arginine), poly (L-lysine, L-alanine), and poly (L-ornithine, L-leucine), on focusing the effect of molecular weight and concentration of the polypeptide on DNA transfection. The transfection activity was examined in terms of the functional transfer of pSV2cat plasmid DNA into HeLaS3 cells. Cell viability was evaluated by measuring the activity of the lactate dehydrogenase (LDH) released from cells. Poly (L-ornithine), poly (L-arginine) and poly (L-ornithine, L-leucine) induced very high expression levels of a foreign gene in HeLaS3 cells. However, poly (L-lysine) and poly (L-lysine, L-alanine) were not effective. Cytotoxicity was observed at high concentrations of polypeptides and increased in the order of poly (L-ornithine) > poly (L-lysine) > poly (L-arginine) ≥ poly (L-ornithine, L-leucine) > poly (L-lysine, L-alanine). The molecular weight of polypeptide also greatly influenced transfection activity. The higher molecular weight of poly (L-ornithine) (MW 203,400) mediated gene transfer most effectively, and its transfection activity were approximately 5-fold higher than that of poly (L-ornithine), with a molecular weight of 53, 600, whereas the poly (L-ornithine) of a lower molecular weight (MW 11,700) exhibited little activity. The optimal concentrations of the polypeptides depended on the DNA level in an applied solution. The optimal mass ratio of DNA/polypeptide for transfection was 0.4-0.8. The transfection activity of a polypeptide depends on its amino acid composition, molecular weight, and DNA/peptide ratio. High molecular poly (L-ornithine) and poly (L-arginine) were more efficient mediators of DNA transfection than Lipofectin, a commercially available reagent.

In order to develop an intravenous formulation of all-trans retinal (vitamin A aldehyde, VAA) for the treatment of night blindness, VAA and dipalmitoylphosphatidylcholine (DPPC) were sonicated and dispersions in the VAA mole fraction range of 0.1-0.7 were stable at room temperature for 3 days. In order to clarify the dispersal mechanism, the interaction between VAA and DPPC was investigated using several physicochemical techniques. Dynamic light scattering measurements showed that the diameter of the dispersed particles was 50-70 nm. A limited amount of VAA was incorporated into DPPC bilayer membranes (approximately 5 mole%). The trapped aqueous space marker calcein and the volume in the VAA/DPPC particles was decreased remarkably into small unilamellar vesicles of DPPC with the addition of VAA. The decline in the fraction of vesicular particles was also confirmed by fluorescence quenching of N-dansylhexadecylamine in the DPPC membrane by the addition of the quencher CuSO₄. These results indicate that the excess VAA separated from the DPPC bilayers was stabilized as suspension particles by the DPPC surface monolayer. The monolayerbilayer equilibrium of VAA/DPPC mixtures was explored by measurements of spreading and collapse pressures.

Commercial green tea leaves were ground to a fine powder with a ceramic mortar and the powder characteristics were determined and evaluated for flowability using Carr's flowability index. The finely powdered green tea (PT) showed high compressibility of 49.1%, and a flowability index of 28.5 (flowability was “Very Poor”). By the addition of Perfiller^®-101, the angle of repose and compressibility decreased and flowability was greatly improved, to the point of being sufficient for handling and dispensing. Released amounts of epigallocatechin gallate (EGCG) and caffeine from PT were about 10 times higher than those of unpowdered commercial green tea leaves. Additionally, the ratio of amount of EGCG to caffeine released from PT was higher than that from unpowdered commercial green tea leaves. Although the 50% release time of caffeine was shorter than that of EGCG from unpowdered commercial green tea leaves, there was little difference in the 50% release time of caffeine and EGCG from PT.

E5880, a novel platelet factor receptor antagonist, was dispersed in a buffer solution (0.1 mg/ml, 10% lactose, pH 2.8) for use in an injectable formulation and the physicochemical properties of the resulting micelles were characterized. The critical micelle concentration of E5880 was 0.12 mM. Using area per molecule data, the critical packing parameter was calculated, and it was indicated that the structure is spherical and that the number of molecules per micelle is 46. The diameter of the micelle was 5.6 nm. The micropolarity around the hydrocarbon region of the micelle was similar to that of isobutanol.

The rectal absorption and hypoglycemic effects of insulin after the administration of poly(vinylalcohol) (PVA) gel suppositories containing insulin and 1% sodium EDTA were investigated in rats. PVA gel suppositories were prepared using the freeze-thaw cycle method. Insulin was administered at a dosage of 12.5 or 25 U/kg. The mutarotase-GOD method was used for measuring plasma glucose levels. An automatic EIA system was employed for measuring plasma insulin levels. After the administration of insulin at 25 U/kg, significant and continuous hypoglycemic effects as well as high plasma insulin concentrations were observed. It is believed that insulin was released from the PVA gel suppository at a constant rate. Our results indicate that PVA gel suppositories are able to maintain low levels of plasma glucose for long periods of time.