Yoshiteru Kato

Studies on the mechanism of printing film-coated tablets containing titanium dioxide in the film by using UV laser irradiation

Aim: The purpose of this article is to study a detailed mechanism of printing when film-coated tablets were irradiated by UV laser at a wavelength of 355 nm. Methods: Hydroxypropylmethylcellulose (HPMC) film containing titanium dioxide (TiO2) and the film not containing TiO2 and TiO2 powder were lirradiated by the UV laser and estimated by the morphological observation by zoom stereo microscope, thermogravimetric analysis (TGA), total color difference (dE), X-ray powder diffraction (XRD), and dispersive Raman microscopy. Results: In the case of the film containing TiO2, the film showed a visible change in its color from white to gray by the UV laser irradiation. By zoom stereo microscope, it was found that the entire UV laser-irradiated area was not grayed uniformly, but many black particles, whose diameter was about 2 μm, were observed on the film. When TiO2 powder was irradiated by the UV laser, a visible change in its color from white to gray was observed similar to the case of the film containing TiO2. There were many black particles locally in the UV laser-treated TiO2 powder by the morphological observation, and these black particles, agglomerates of the grayed oxygen-defected TiO2, were associated with the visible change of the TiO2. Conclusion: It was found that the film-coated tablets were printed utilizing the formation of the black particles by the agglomeration of the grayed oxygen-defected TiO2 by the UV laser irradiation.

Further Observation of Content Uniformity of d-α-Tocopheryl Acetate as an Oily Drug in Granules Obtained by Wet Granulation with a High-Shear Mixer

Using d-α-tocopheryl acetate (VE) as a model drug, we investigated the effects of the amount of binder solution on content uniformity of oily drugs in granules obtained by wet granulation with a high-shear mixer. When the amount of binder solution was below the water volume for the plastic limit, the content of VE was less than 50% in the fractionated fine granules, but was more than 200% in the fractionated large granules. Large variations were seen in the contents of VE even if the granulation time was extended up to 30 min. This large variation was not decreased by the milling process. On the other hand, when the amount of binder solution was at or above the water volume for the plastic limit, less variation was observed in the content of VE throughout the granules, and the content of VE was fairly uniform. Nuclei rich in VE were formed when VE was adsorbed with the powder before granulation. When the amount of binder solution was below the water volume for the plastic limit, the shearing force of mixer blades to the granules was low, so that the nuclei rich in VE were not fragmented. This led to the nonuniformity of VE content throughout the granules. On the other hand, when amount of binder solution was at or above the water volume for the plastic limit, the shearing force of mixer blades against the granules increased and became sufficient to fragment the nuclei. This led to the uniformity of VE content throughout the granules. This study showed that content uniformity of VE in the granules can be achieved by controlling the physical shearing force of mixer blades by regulating the amount of binder solution.

Effect of water-Insoluble Powder Addition on Physical Properties of Gelatin Gel

AbstractWater-insoluble powder is often dispersed in shells of commercial soft capsules for various reasons, but little reports have been published about the effect of powder addition on the physical properties of the gelatin gel. Glass powder, titanium oxide, calcium carbonate and γ-orizanol were used as model of powder. Changes of Young modulus obtained from the tensile test showed that any powder addition to the gelatin sheet made the gelatin sheet hard not by the surface effect of powder but by the volumetric effect of it. In this test, any powders had no effect on the tensile strength of the gelatin sheet because there was little interaction between each powder and the gelatin gel in the break point. The limiting strain was decreased a little up to the specific amount of each powder and then beyond the specific amount that decreased steeply in the case of glass powder and γ-orizanol. There might be a suitable range of the amount of powder for the gelatin sheet to keep the plastic flow similar to the ...

Evaluation of Risk and Benefit in the Application of Near-Infrared Spectroscopy to Monitor the Granule Coating Process

The purpose of this article is to study risk and benefit in the application of near-infrared (NIR) spectroscopy to the coating process of granules to monitor the process for determining the coating end point. Cylindrical granules or spherical granules were used as core granules and were coated using a fluidized bed coating apparatus by spraying coating suspension. During the coating run, samples of granules were pulled at regular intervals and amount of talc or lactose, which were the components of the film layer, were estimated by NIR spectroscopy. When the coating layer of granules was thin like the case of the spherical granules, it was possible to monitor and understand the coating process well by an application of NIR spectroscopy, because it was possible to estimate some components in the coating layer simultaneously. However, it was found that as the coating layer became thick like the case of the cylindrical granules, NIR light was scattered by titanium dioxide in the coating layer, and that the increase of the coating layer estimated from NIR spectroscopy showed the misunderstanding saturation. NIR spectroscopy could not be used for the estimation of the granule coating process even if the formulation and amount applied for the coating was same as the spherical granules. When NIR spectroscopy is intended to be used to control granule coating process, it is necessary to check the impacts of the formulation applied for coating, the amount of the coating layer, and the thickness of the coating layer on the estimations.

Imprinting on empty hard gelatin capsule shells containing titanium dioxide by application of the UV laser printing technique

Abstract The purpose of this study was to examine the application of ultraviolet (UV) laser irradiation to printing hard gelatin capsule shells containing titanium dioxide (TiO2) and to clarify how the color strength of the printing by the laser could be controlled by the power of the irradiated laser. Hard gelatin capsule shells containing 3.5% TiO2 were used in this study. The capsules were irradiated with pulsed UV laser at a wavelength of 355 nm. The color strength of the printed capsule was determined by a spectrophotometer as total color difference (dE). The capsules could be printed gray by the UV laser. The formation of many black particles which were agglomerates of oxygen-defected TiO2 was associated with the printing. In the relationship between laser peak power of a pulse and dE, there were two inflection points. The lower point was the minimal laser peak power to form the black particles and was constant regardless of the dosage forms, for example film-coated tablets, soft gelatin capsules and hard gelatin capsules. The upper point was the minimal laser peak power to form micro-bubbles in the shells and was variable with the formulation. From the lower point to the upper point, the capsules were printed gray and the dE of the printing increased linearly with the laser peak power. Hard gelatin capsule shells containing TiO2 could be printed gray using the UV laser printing technique. The color strength of the printing could be controlled by regulating the laser energy between the two inflection points.

Factors affecting color strength of printing on film-coated tablets by UV laser irradiation: TiO2 particle size, crystal structure, or concentration in the film, and the irradiated UV laser power

Aim: The purpose of this article is to study factors affecting color strength of printing on film-coated tablets by ultraviolet (UV) laser irradiation: particle size, crystal structure, or concentration of titanium dioxide (TiO2) in film, and irradiated UV laser power. Methods: Hydroxypropylmethylcellulose films containing 4.0% of TiO2, of which BET particle sizes were ranging from 126.1 to 219.8 nm, were irradiated 3.14 W of UV laser at a wavelength 355 nm to study effects of TiO2 particle size and crystal structure on the printing. The films containing TiO2 concentration ranging from 1.0 to 7.7% were irradiated 3.14 or 5.39 W of the UV laser to study effect of TiO2 concentration on the printing. The film containing 4.0% of TiO2, was irradiated the UV laser up to 6.42 W to study effect of the UV laser power on the printing. The color strength of the printed films was estimated by a spectrophotometer as total color difference (dE). Results: Particle size, crystal structure, and concentration of TiO2 in the films did not affect the printing. In the relationship between the irradiated UV laser power and dE, there found an inflection point (1.6 W). When the UV laser power was below 1.6 W, the films were not printed. When it was beyond the point, total color difference increased linearly in proportion with the irradiated laser power. Conclusions: The color strength of the printing on film was not changed by TiO2 particle size, crystal structure, and concentration, but could be controlled by regulating the irradiated UV laser power beyond the inflection point.

Application of the UV laser printing technique to soft gelatin capsules containing titanium dioxide in the shells

Aim: The purpose of this study was to examine application of ultraviolet (UV) laser irradiation to printing soft gelatin capsules containing titanium dioxide (TiO2) in the shells and to study effect of UV laser power on the color strength of printing on the soft gelatin capsules. Methods: Size 6 Oval type soft gelatin capsules of which shells contained 0.685% TiO2 and 0.005% ferric dioxide were used in this study. The capsules were irradiated pulsed UV laser at a wavelength 355 nm. The color strength of the printed capsules was determined by a spectrophotometer as total color difference (dE). Results: The soft gelatin capsules which contained TiO2 in the shells could be printed gray by the laser. Many black particles, which were associated with the printing, were formed at the colored parts of the shells. It was found that there were two inflection points in relationship between output laser energy of a pulse and dE. Below the lower point, the capsules were not printed. From the lower point to the upper point, the capsules were printed gray and total color difference of the printing increased linearly in proportion with the output laser energy. Beyond the upper point, total color difference showed saturation because of micro-bubbles formation at the laser irradiated spot. Conclusions: Soft gelatin capsules containing TiO2 in the shells could be performed stable printing using the UV laser printing technique. Color strength of the printing could be controlled by regulating the laser energy between the two inflection points.

Improvement of content uniformity of d-α-tocopheryl acetate as an oily drug in granules by emulsification

ABSTRACT To elucidate the effects of an oily drug emulsification on its content uniformity in granules obtained by wet granulation with a high-shear mixer, d-α-tocopheryl acetate (VE) was emulsified with hydroxypropylcellulose (HPC-L) solution (mean diameter of the VE droplets was 1.3 μm). When VE was added to the mixing powder as the emulsion, nuclei rich in VE were not formed and then the content of VE was fairly uniform throughout the granules even at 2 min granulation. We found that the oily drug poor content uniformity could be improved significantly by adding an emulsified drug to the powder in granulation process.

Effects of Oily Drug Rheology on Content Uniformity in Granules Obtained by Wet Granulation with a High‐Shear Mixer

The purpose of the present work was to elucidate the effects of viscosity on the content uniformity of an oily drug in granules obtained by wet granulation with a high‐shear mixer. For this purpose, we used d‐α‐tocopheryl acetate diluted with a medium chain fatty acid triglyceride having viscosities in the range from 26.0 to 726.0 mPas. It was found that independent of viscosity, nuclei rich in the oily drug were formed in the process of mixing with powder and that those nuclei prevented uniform distribution of the drug throughout the granules. To achieve content uniformity, it is necessary for the nuclei formed before granulation to be fragmented and for the oily drug to be distributed uniformly throughout granules. Tensile strength of the nuclei was attributed to the viscosity of the oily drug, according to a model for tensile strength of a granule under dynamic conditions. When viscosity of the oily drug increased, tensile strength of the nuclei increased and the extent of the drug demixing in granules was large and constant independent of granulation time. On the other hand, when viscosity of the oily drug decreased, tensile strength of the nuclei decreased. The extent of the drug demixing was small with lower viscosity but increased with a prolonged granulation time. In the case of the oily drug, we found that a decrease in its viscosity led to the improvement of the content uniformity in granules. The viscosity of the oily drug significantly affects its content uniformity in granules by a high‐shear mixer granulation.

Evaluation of risk and benefit in thermal effusivity sensor for monitoring lubrication process in pharmaceutical product manufacturing

Abstract In the process design of tablet manufacturing, understanding and control of the lubrication process is important from various viewpoints. A detailed analysis of thermal effusivity data in the lubrication process was conducted in this study. In addition, we evaluated the risk and benefit in the lubrication process by a detailed investigation. It was found that monitoring of thermal effusivity detected mainly the physical change of bulk density, which was changed by dispersal of the lubricant and the coating powder particle by the lubricant. The monitoring of thermal effusivity was almost the monitoring of bulk density, thermal effusivity could have a high correlation with tablet hardness. Moreover, as thermal effusivity sensor could detect not only the change of the conventional bulk density but also the fractional change of thermal conductivity and thermal capacity, two-phase progress of lubrication process could be revealed. However, each contribution of density, thermal conductivity, or heat capacity to thermal effusivity has the risk of fluctuation by formulation. After carefully considering the change factor with the risk to be changed by formulation, thermal effusivity sensor can be a useful tool for monitoring as process analytical technology, estimating tablet hardness and investigating the detailed mechanism of the lubrication process.