Tetsurou Handa

Enhancement of the dissolution rate of a poorly water-soluble drug (tolbutamide) by a spray-drying solvent deposition method and disintegrants

The dissolution rate of a poorly water‐soluble drug, tolbutamide, was improved by spray‐drying a diluted ammonia solution of the drug containing either a low‐substituted hydroxypropylcellulose (L‐HPC) or partly pregelatinized corn starch (PCS) as disintegrants. With L‐HPC the resultant particles were agglomerates of disintegrant with drug on the surface and within the particles, while particles formed with PCS were composed of a single core of PCS on which the drug was deposited. The deposited drug crystals were very fine because the rapid solvent evaporation restricted crystal growth. The spray‐dried particles prepared with PCS had a structure similar to that of an ordered mix. The drug dissolution rate from the spray‐dried particles was more rapid than that of the powdered drug alone or with disintegrant and could be attributed to separation of the layer of fine drug crystals from the surface of the particles by swelling of disintegrant. PCS enhanced the drug dissolution rate compared with systems using corn starch. The dissolution rate also depended on the drug content of the particles which was higher than that in ordered mixtures or conventional solvent deposition systems. This system described also had the advantage of avoiding the use of organic solvents.

Controlled Release Theophylline Tablet with Acrylic Polymers Prepared by Spray-Drying Technique in Aqueous System

AbstractSustained release and enteric theophylline tablets were prepared by directly compressing spray-dried microsphers with Eudragits L30D, L100-55 and E30D. The spray-drying process was free from using organic solvent. Drug dissolution of the enteric tablet in an acidic solution (pH 1.2) was highly dependent on the polymer content of the microsphere. Completely enteric function was observed with drug-to-polymer ratio of 1:3 using Eudragit L30D or L100-55. Tablet with Eudragit E30D formulated at the 2–40% level showed good sustained drug release which was throughly independent of the pH of dissolution media. The dissolution pattern was similar to that of Theo-dur and gave a straight line in Higuchi plot. In each tablet, the controlled drug release was attributed to continuous and well-dispersed polymer matrix formed by spray-drying and subsequent compressing process

Effects of lysophosphatidylcholine micelle and phosphatidylcholine liposome on photoreduction of methylviologen

Photoinduced reduction of methylviologen (MV2+) by ethylenediaminetetraacetate (EDTA3-), which was sensitized by thiacarbocyanine dyes having long alkyl chains (C+m-n) embedded in palmitoyl lysophosphatidylcholine micelle and dipalmitoyl phosphatidylcholine liposomal membrane, was carried out. The formation rate of reduced methylviologen cation radical (MV+.) decreased with the time of irradiation with visible light, and the deceleration was more pronounced in the micellar solution. In kinetic studies, we found that the sensitizer divalent cation radical (C2+.m-n) is formed through the reaction of photoexcited sensitizer (C+*m-n) with MV2+ as an intermediate in this reaction, and that the reduction of C2+.m-n with EDTA3- inhibits the back reaction of MV+. with C2+.m-n. The inhibition was greater in the liposomal solution than in the micellar solution. This was ascribed to a higher concentration of EDTA3- on the liposomal surfaces through the electrostatic interaction between EDTA3- and the liposomal surfaces, the charge of which is attributed to the univalent cation sensitizer embedded in the liposomal membrane. The difference in the positive charge density of the surface of these lipid aggregates was due to the difference in the curvature of the micelle and the liposome. These results suggest that the dipalmitoyl phosphatidylcholine liposome is a more effective carrier than the palmitoyl lysophosphatidylcholine micelle for the production of MV+. in the photoreduction studied here.