Kaori Jono

A review of particulate design for pharmaceutical powders and their production by spouted bed coating

Abstract This paper focuses on how fine particles are processed in a fluidized/spouted bed coater without agglomeration and what kinds of functions are desired for particulate dosage forms, in order to preview the future contributions of fluidization technology in pharmaceutical dosage form development. Coating operation of particles smaller than 100 μm is very often troubled with particle agglomeration and adhesion due to the excessively high binding strength of coating materials and to electrostatic charging. In order to avoid these troubles, the binding strength has to be adjusted corresponding to the size of particles to be processed. The most efficient way to produce single-core microcapsules is to separate the drying and film formation of spray droplets. This can be achieved by using latices whose softening temperature (Ts) is higher than the inlet air temperature. Particulate designs of the latex polymers based on this idea are also effective for solving some other troubles such as electrostatic charging and poor film formability in fine particle coating. Meanwhile, multiple functions and high performance are required for particulate systems to exhibit desired characteristics in practical uses. The fluidized/spouted bed process, which can easily produce multi-layered and composite structures, is an excellent method for multi-functional adaptation of particulate systems. This is demonstrated in this paper in the preparation of microcapsules for cancer therapies, such as neutron capture therapy (NCT) and chemoembolization therapy, and for stimuli-sensitive controlled-release therapy. In pharmaceutical technology, requirements for producing functional particles of around 30 μm, which can be used, for example, as injectable suspensions for cancer therapy, will increase in the future. This will require the processing of around 10-μm particles, though the smallest particle size that a fluidized/spouted bed can steadily process seems to be 20 μm so far. Membrane and core formulations to process such fine particles seem available already, but we have no technique to steadily fluidize or circulate 10-μm particles at high velocity in a dispersed condition. Furthermore, nanoparticulate systems will be required for more efficient cancer treatments. Although the fluidized/spouted bed is unable to process nanoparticles directly, development of some smart devices as their generators will be made possible by its high potential to make multi-layered and composite structures.

Dry grinding of chitosan powder by a planetary ball mill

Dry grinding of chitosan powder was carried out using a planetary ball mill for its applications to drug carriers. Eighty grams of zirconium oxide balls of 1-5 mm diameter and 1-4 g of 100% deacetylated chitosan were loaded into a 45 ml agate pot and then ground at 440-723 r.p.m. The particle size was analyzed by a laser scattering diffraction method. When surface grinding was induced by lower rotation speeds and smaller beads, except for I mm balls, the chitosan powder was ground at a lower rate, but to a smaller size. The median diameter of the powder ground without any additives was minimized to 5.0 μm at 440 r.p.m. rotation speed using 2 mm balls. Further, various additives were tested to find an effective material as a grinding aid. Hydrophobic compounds, including fatty acids with a long acyl chain and cholesterol, and hydrophilic polyethylene glycol 4000 were effective to reduce the particle size. Lauryl compounds with the same number of carbons exhibited almost the same size reducing effect as a grinding aid, regardless of polar head groups, consisting of carboxylic acid, alcohol or amine. The optimal content was 10-20% in the case of lauric acid. Fatty acids with a longer acyl chain were more effective as a grinding aid. Among the additives studied, stearic acid was most effective and reduced the median diameter to 1.8 μm.

Dissolution properties of gadolinium-containing lecithin microcapsules prepared by a spouted bed process assisted with a draft

Abstract Gadolinium (Gd)-containing lecithin microcapsules were composed of a lactose core (75-90 μm) coated with polyvinylpyrrolidone (PVP), a drug layer of Gd compound and PVP, and a membrane consisting of soybean lecithin, cholesterol, stearic acid and PVP. As Gd compounds, gadopentetate dimeglumin (Gd-DTPA-DM, MC-1), gadopentetic acid (Gd-DTPA, MC-2) and a stearylamide derivative of Gd-DTPA (Gd-DTPA-SAm, MC-3) were used. The microcapsules were prepared with a high coating efficiency and a narrow size distribution, 149-177 μm. The release Gd-DTPA-DM and Gd-DTPA from MC-1 and MC-2, respectively, in a 0.9% saline solution was similar in spite of their difference in water solubility; it was delayed with a short lag time of about 10 min, followed by a rapid release and finally sustained; on the other hand, the release was remarkedly delayed and prolonged without the initial rapid release in the dextran solution. The release of water-insoluble Gd-DTPA-SAm was almost completely suppressed until 120 min in both aqueous solutions (MC-3). In the saline solution, all types of Gd-containing microcapsules were bursting devices at the initial stage, accompanying the delayed but high particle swelling, and thereafter diffusion-controlled drug-release devices. In the viscous dextran solution, they remained diffusion-controlled drug-release devices due to poor water uptake and poor swelling. These results suggested the possibility for using Gd-containing lecithin microcapsules in Gd neutron-capture therapy.