Takafumi Ishizaka

Preparation of Drug-Diluent Hybrid Powders by Dry Processing

New hybrid powders have been produced by the dry processing of six drugs (oxyphenbutazone, prednisolone, theophylline, indomethacin, phenacetin and aspirin), with potato starch used as a core material, by means of an electric mortar and a powder suface reforming system designed to produce hybrid powders. The hybrid powders obtained immediately after production differed in their structure from interactive mixtures. With the hybrid powders the drug was spread on the surface of the core particle by friction and collision that occurred in the dry process, but with interactive mixtures the drug simply adhered as intact particles to the surface of diluent particles. Scanning electron microscopy and powder X‐ray diffractometry indicated that the mechanochemical phenomenon was essential for the production of the hybrid powders. With time, a shape change in the adhering drug was observed as a relaxation process took place, with recrystallization resulting from the release of accumulated energy. The change with time might depend upon the method of producing powders and the physical properties of the drug used, e.g. the smooth layer of indomethacin produced by the powder surface reforming system reverted to fine particles tightly adhering to the starch surface, though no change was observed with prednisolone.

Permeability of polyamide microcapsules toward ions and the effect of water structure

Abstract Permeability coefficients for sodium, potassium, and rubidium hydroxide in poly(1,4-terephthaloylpiperazine) and poly(1,6-hexamethylenesebacamide) microcapsules were determined in order to examine the effect of water structure on the permeation of ions through microcapsule membranes. p]The results show that, with increasing proportion of cyclohexane in the mixed solvent used in the preparation of the microcapsules, the membrane thickness of the microcapsules increases and the permeability coefficient decreases. The difference between the permeability of poly(1,4-terephthaloylpiperazine) and poly(1,6-hexamethylenesebacamide) microcapsules was clearly demonstrated. The permeability was measured using three alkali hydroxides (NaOH, KOH, and RbOH). Potassium hydroxide permeated through the microcapsules about three times faster than sodium hydroxide and about an order of magnitude faster than rubidium hydroxide, under comparable conditions. The water structure was determined from the thermal behavior of aqueous microcapsule suspensions, which was studied by differential scanning calorimetry. The thermal behavior of the suspensions and the permeability of the microcapsules were found to change when urea was added to the suspensions. It was concluded that the ion permeation closely related to the water structure in and around the microcapsule membrane.

Drug dissolution from indomethacin-starch hybrid powders prepared by the dry impact blending method

Abstract— Indomethacin was hybridized with potato starch using a dry impact blending method. Resultant hybrid powders were investigated by scanning electron microscopy and X‐ray powder diffraction. Amorphous indomethacin spread over the starch surface in a layer immediately after being hybridized, and then gradually reverted to fine crystalline particles adhering firmly to the starch surface. Indomethacin dissolution from the hybrid powder was compared with those from physical mixtures and granules taken from a commercially available capsule. Indomethacin dissolution from powder and capsule dosage forms, even in an acidic medium, was drastically accelerated by the hybridization.