Hideo Takenaka

The physicochemical parameters determining the size of agglomerate prepared by the wet spherical agglomeration technique

Abstract Lactose samples of five different particle sizes from 31 to 261 μm dispersed in chloroform were agglomerated with a small amount of saturated aqueous lactose solution which acted as a bridging liquid to wet the particles preferentially. The effects of raw particle size and the amount of bridging liquid on the average size of resultant agglomerate were investigated. The agglomerate size increased with decreasing size of lactose. This effect was enhanced by increasing the amount of bridging liquid for lactose less than 79 μm. A linear correlation on a log—log plot was observed between the agglomerate size and the saturation ratio of bridging liquid. The slope increased with decreasing particle size of lactose. The size distribution of agglomerates was also determined for the particle size of lactose and the amount of bridging liquid used. The physicochemical properties of the bridging liquid, i.e. contact angle and interfacial tension, were also taken into account for interpreting the agglomerate size. The correlation between the agglomerate size and the above parameters was represented quantitatively by eqn. (10) in the text. The parameter n, which varies directly with agglomerate size, increased with increasing saturation ratio, or with decreasing lactose particle size.

Drug Release Properties of the Microcapsules of Adriamycin Hydrochloride with Ethylcellulose Prepared by a Phase Separation Technique

AbstractAdriamycin hydrochloride was microencapsulated with ethylcellulose by a phase separation method to develop a prolonged release dosage form. Polyisobutylene (PIB) was used as a coacervation-inducing agent to control the particle size and drug release rate of the resultant microcapsules. With increasing the concentration of PIB (1 to 3 %) the average diameter of the microcapsules decreased, due to the fact that the microcapsules were discreted to a single microcapsule. At low concentration of PIB, the resultant microcapsules were agglomerated, which resulted in increasing the size. The microcapsules prepared with PIB 2 % prolonged desirably the drug release from the microcapsules. A little size effects of the microcapsules on the drug release rate was found for the microcapsules with PIB 2 % and 3 %.

Preparation of spherical wax matrices of sulfamethoxazole by wet spherical agglomeration technique using a CMSMPR agglomerator

Abstract Spherical wax matrices of sulfamethoxazole were prepared by a wet spherical agglomeration technique using a model continuous mixed suspension mixed product removal (CMSMPR) agglomerator to develop a practical continuous operation system. The average diameter of products increased at the initial stage of operation until reaching a maximum at 5 to 7 minutes elapsed after starting. This maximum point roughly corresponded to a half of average retention time. Thereafter the particle size decreased gradually and reached the equilibrium state. The average size of products obtained at steady state decreased on decreasing the feeding rate of bridging liquid, but increased on decreasing the agitation speed and the feeding rate of aqueous suspension. The rate of agglomeration was analysed using the concept of population balance proposed by Randolph and Sikdar. The agglomeration rate increased with increase of particle size for sizes above 200 – 300 μm. For sizes below 200 μm, the agglomeration rate was almost independent of particle size.

Polymorphism and drug release behavior of spray-dried microcapsules of sulfamethoxazole with polysaccharide gum and colloidal silica

AbstractSulfamethoxazole microcapsules with polysaccharide gum, i.e. xanthan gum and guar gum, were prepared by employing a spray drying technique. The aqueous or the ammonium hydroxide solution of the gum containing the drug with or without colloidal silica was atomized with a centrifugal wheel atomizer rotated at 40000 rpm into a drying chamber held at 140±10°C. By formulation with colloidal silica, particle size of the resultant product increased, leading to improve the flowability and packability for the tableting. Polymorphic sulfamethoxazole mixture of Form I, II and III was produced in the formulation with cellulose acetate

Preparations of Solid Particulates of Amino-Pyrine-Barbital Complex (Pyrabital) wiithout Autoxidation Ey a Spray Drying Technique

AbstractAminopyrine, barbital and colloidal silica dispersed in buffer solutions having pH 5.46 to 8.01 were spray-dried by a centrifugal wheel atomizer at 130 ± 5°C. When the pH of the feeding liquid for spray drying was 5.70 to 7.24, the resultant product was a mixture of amlnopyrine-barbital complex (pyrabital), aminopyrine and the exci-pient. When the pH was lower than 5.84 or higher than 7.84, barbital or sodium barbital coexisted in the above mixture products. Autoxidation of aminopyrine occurred during the spray drying was greatly prevented by introducing chelating agent, e.g. ethylenediaminetetraacetic acid and glycine, or antioxidation agent, e.g. sodium thiosulfate and citric acid in the feeding liquid. It was also found that reducing the pH of the feeding liquid effectively depressed the autoxidation of aminopyrine.

Some Physicochemical Characteristics of Agglomerates and Microcapsules of Sulfisomidine Spray-Dried from Aqueous Slurries and Ammonium Solutions

AbstractAqueous slurries or ammonium solutions of sulfiso-rnidine containing various kinds of binder, i.e. acacia, gelatin, carboxymethylcellulose, methylcellulose or poly-vinylpyrrolidone were spray dried using a centrifugal wheel atomizer. The spray-dried products were found by scanning electron microscopy observation to be agglomerated or encapsulated. The products prepared from the aqueous slurries were microcapsules coated with a smooth film, whilst the products from ammonium solutions were agglomerates with porous agglomerating crusts on their surfaces. Micromeritic properties such as, particle diameter, flow and packing properties, etc. were investigated. Infrared absorption spectra confirmed that the spray-dried ammonium sulfisomidine was converted to the non-salt form during drying. X-ray diffraction patterns were obtained to investigate the crystalline forms and to determine the degree of crystallinity of spray-dried sulfisomidine. Solubilities of the products were measured in distilled water an...

Measurement of Cohesive Force of Moist Powder in Air and Liquid by a Diametrical Compression Technique

The measurement of cohesive force of moist powder was intended in liquid as well as in air. A diametrical compression technique was assumed to achieve the measurement even in liquid comparatively with ease. The suitability of the diametrical compression technique for measuring the cohesive force of moist powder was examined by comparing the cohesive force in air with that measured by a traction table method using moist precipitated calcium carbonate. The cohesive force at the contact point of moist powder bed was determined using the data of calcium carbonate and microcrystalline cellulose obtained by the compression test. In a pendular region of moistening liquid, the cohesive force at the contact point increased with increasing the filling ratio of liquid to the void in powder bed. While in the funicular region, it decreased gradually with increasing the filling ratio, which indicates that the structure of powder bed became heterogeneous due to the formation of agglomerates. This argument was confirmed by observing the resultant failure plane of the moist powder bed at the funicular state brought about by compressing. The above result indicates that the cohesive force measured at the pendular state is the intrinsic value of the primary particle but only apparent at the funicular state. The cohesive of moist bed of precipitated calcium carbonate in carbon tetrachloride was found to be smaller than that in air. This result was explained by the depression of interfacial tension of moistening liquid in carbon tetrachloride compared to that in air.

Flow Properties of Fed-slurries Containing Sodium Salicylate and Salicylic Acid Particles

The flow properties of aqueous slurries containing salicylic acid, sodium salicylate and gum arabic, prepared as feed-liquids into spray drying chamber, were investigated by analysis of their flow curves obtained using a cone and plate viscometer. Their flow curves showed a thixotropy, having two Newtonian flow curves at low and high shear rates and a characteristic spur-like protrusion between two Newtonian flow curves. Spur in their curves is thought to result from a sharp breakdown point in the card-house structure in slurry at the movement of salicylic acid particles. Apparent viscosity of the first Newtonian flow (ηN1) at the low shear rate was larger than that (ηN2) of the second Newtonian flow and was related to sedimentation volume of salicylic acid only. The second Newtonian apparent viscosity was related to concentrations of gum arabic and sodium salicylate, and active energy for it was 3-12kcal/mol. When geometric mean diameters of salicylic acid particles in slurries were large, or geometric standard deviations of distributions or shape factors of them were small, thixotropy coefficients (ηR=ηN1/ηN2) were large and represented resistance for movement of solid particles in slurries to be large at the low rate of shear. When the distribution of solid particles were broad and shape factor of them were large, small and narrow particles act as glidants or rollers to facilitate the rotation of larger particles resulting in the reduction of the thixotropy of slurry.

Particle Properties of Spray-Dried and Agglomerated Products of Salicylic Acid and Sodium Salicylate

The aqueous slurries of salicylic acid and sodium salicylate containing various kinds of binder, e.g. gum arabic, gelatin, polyvinyl alcohol, carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone, tragacanth and sodium alginate, were spray-dried using a centrifugal wheel atomizer. Almost all of the agglomerated products are fine granules having a diameter of 15-100μ, compared with 1-8μ for the original salicylic acid, and are fairly free flowing. It is the case with polyvinylpyrrolidone and gum arabic products.The particle properties, such as diameter, true density, sphericity and surface area were measured, all of these being strongly influenced by the concentrations of sodium salicylate and binder. The surface topography of the products was studied with a scanning electron mciroscope. Gum arabic and polyvinylpyrrolidone products had smooth surfaces without holes or craters. Granules borne with other binders showed characteristic surfaces having craters of 5-10μ. The analysis of the X-ray diffraction patterns and the infrared absorption spectrum of products showed that gum arabic and polyvinylpyrrolidone granules still contained both salicylic acid and sodium salicylate, in contrast to the cases where other binders were used, where only sodium salicylate remained, the salicylic acid having sublimed. Gum arabic and polyvinylpyrrolidone products are microcapsules containing salicylic acid and sodium salicylate of grain size of about 200-800A, amorphous contents of about 50-80% and grain size of about 130-170A, polymorphism including original crystalline form of 3-20% respectively. The thickness of the encapsulating film is 1-3μ. Finally, the change in appearance of a drying slurry droplet is discussed and two typical drying processes, namely agglomerated crust and encapsulating film formation, are described.