Nov. 2023

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Oct. 2021

Sep. 2018

Oct. 2017

Oct. 2011

Evaluation of the Film-Forming Ability for Heparinoid Cream Formulations
Niina Shikamura; Toshiro Fukami; Tatsuo Koide; Yoshihisa Yamamoto
Chemical & Pharmaceutical Bulletin, Sep. 2025, [Reviewed]

Quantitative Relationship between the Viscosity of Pediatric Syrups Containing Ambroxol Hydrochloride and the Adhesive Remaining Amount in the Metering Glass
Taiki Nagatomo; Mihiro Kanai; Mitsuyoshi Fukuda; Manabu Shimazaki; Yoshihisa Yamamoto; Naoto Suzuki; Kaname Hashizaki; Toyofumi Suzuki
J. Community Pharmacy Pharm. Sci., Apr. 2025, [Reviewed]

Pharmaceutical Evaluation of Magnesium Oxide Fine Granule Formulation for Conversion to Magnesium Hydroxide owing to Humidification by Near-Infrared Spectroscopy
Yoshihisa Yamamoto; Mayo Mitani; Toshiro Fukami; Tatsuo Koide
Vibrational Spectroscopy, Mar. 2025, [Reviewed]

Pharmaceutical Evaluation of Levofloxacin Orally Disintegrating Tablet Formulation Using Low Frequency Raman Spectroscopy
Yoshihisa Yamamoto; Mizuho Kajita; Yutaro Hirose; Naoki Shimada; Toshiro Fukami; Tatsuo Koide
Pharmaceutics, 29 Jul. 2023, [Reviewed]
We evaluated the pharmaceutical properties of levofloxacin (LV) in the form of an orally disintegrating tablet (LVODT) to find a new usefulness of low frequency (LF) Raman spectroscopy. LVODT contained dispersed granules with diameters in the order of several hundred micrometers, which were composed of the active pharmaceutical ingredient (API), as confirmed by infrared (IR) microspectroscopy. On the contrary, the API and inactive pharmaceutical ingredients (non-APIs) were homogeneously distributed in LV tablet (LVT) formulations. Microscopic IR spectroscopy and thermal analyses showed that LVODT and LVT contained the API in different crystalline forms or environment around the API each other. Furthermore, powder X-ray diffraction showed that LVT contained a hemihydrate of the API, while LVODT showed a partial transition to the monohydrate form. This result was confirmed by microscopic LF Raman spectroscopy. Moreover, this method confirmed the presence of thin layers coating the outer edges of the granules that contained the API. Spectra obtained from these thin layers indicated the presence of titanium dioxide, suggesting that the layers coexisted with a polymer that masks the bitterness of API. The microscopic LF Raman spectroscopy results in this study indicated new applications of this method in pharmaceutical science.

Quality Evaluation of Humidified Magnesium Oxide Tablet Formulations with Respect to Disintegration Time Prolongation.
Yoshihisa Yamamoto; Kosuke Ohgi; Yoshinori Onuki; Toshiro Fukami; Tatsuo Koide
Chemical & pharmaceutical bulletin, 2023
In the present study, we conducted a detailed evaluation of the effects of humidification on the quality of five types of commercial magnesium oxide (MgO) tablet formulations. When near-IR spectroscopy was performed, a peak derived from the first overtone of the stretching vibration of the hydroxyl group was observed at approximately 7200 cm-1 in a humidified MgO tablet formulation. To visually evaluate the effect of this humidification, a mapping image was created using microscopic IR spectroscopy. In the IR spectrum, a peak derived from the stretching vibration of the hydroxyl group appears at approximately 3700 cm-1, so we created a mapping image using the absorbance ratio of 3700 and 3400 cm-1 as an index. In the mapping image of humidified MgO tablet formulations, many areas had a higher absorbance ratio than the dried tablet formulations. From these results, it is qualitatively confirmed that the MgO was changed to magnesium hydroxide (Mg(OH)2) by humidification. Although these results were observed in the four types of MgO tablet formulations, only one type of tablet formulation was less affected by humidification. In addition, although most tablet formulations tended to prolong disintegration time due to humidification, there was almost no effect of humidification on the disintegration time in one type of tablet formulation, which had little change in the above evaluation. Thus, in most commercial MgO tablet formulations, humidification prolongs the disintegration time, and Mg(OH)2 significantly contributes to this factor.

[Evaluation of the Pharmaceutical Properties of Clobetasol Propionate Ointments and Base Stability of the Mixture with Heparinoid Oil Based Creams].
Yoshihisa Yamamoto; Misaki Hata; Saki Tanaka; Nanami Haraguchi; Naoto Suzuki; Toshiro Fukami; Tatsuo Koide
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 01 Apr. 2022, [Reviewed]
Clobetasol propionate ointment (CLPO) formulations have been classified as members of the "strongest" steroidal efficacy group, with eight of these formulations currently marketed in Japan. Evaluations of pharmaceutical properties of each formulation revealed three classification types: droplet dispersion type containing propylene glycol (PG) and surfactant, type with surfactant but not PG, and other types. These rheological properties were diverse, with no correlation found between viscosity and ointment type. However, when CLPO and six types of heparinoid oil-based cream (HPOC) formulation mixtures were stored at 37℃, a liquid layer was observed starting at 24 h for one CLPO formulation in which polyoxyethylene hydrogenated castor oil 40 was used as a surfactant out of the four droplet-dispersion type ointments and two low-viscosity HPOC formulations. In contrast, one other type of CLPO formulation that contained a surfactant with polysorbate 80, but not PG, exhibited a liquid layer for all of HPOC formulations. This suggests that CLPO formulations that contain a surfactant with a high hydrophilic-lipophilic balance value are likely to generate a liquid layer for mixtures containing HPOC formulation. The present results demonstrate that not only the pharmaceutical properties of the eight CLPO formulations differ from one another, but also that the stabilities of HPOC formulation mixtures are significantly different. Therefore, pharmacists need to focus on inactive as well as active pharmaceutical ingredients to select formulations that patients will want to use, in addition to successfully treating their pathological conditions.

Evaluation of the factors contributing to the stability of the mixture of heparinoid oil-based cream and droplet dispersion-type ointment
Yoshihisa Yamamoto; Ayane Ozutsumi; Emina Miwa; Toshiro Fukami; Tatsuo Koide
Journal of Drug Delivery Science and Technology, Feb. 2021, [Reviewed]

Determining the Distribution of Active Pharmaceutical Ingredients in Combination Tablets Using Near IR and Low-Frequency Raman Spectroscopy Imaging.
Hiroshi Hisada; Akira Okayama; Takuya Hoshino; James Carriere; Tatsuo Koide; Yoshihisa Yamamoto; Toshiro Fukami
Chemical & pharmaceutical bulletin, 2020
Combination tablets containing multiple active pharmaceutical ingredients (APIs) are expected to improve patient convenience by decreasing the number of tablets to be taken; thus, numerous formulations containing multiple APIs have recently been developed. To allow for dose adjustments based on patient conditions, many tablets have a bisection line to allow equal division of tablets. However, there have been no investigations regarding content uniformity among divided combination tablets. Therefore, in this study, the content uniformity of combination tablets after division was investigated using near IR and low-frequency (LF) Raman spectroscopy imaging as well as the Japanese Pharmacopoeia (JP) content uniformity tests. As model drugs, five tablets of three combination drugs containing 3-(3,4-dihydroxyphenyl)-L-alanine (L-DOPA) and benserazide hydrochloride (BNS) as APIs for treating Parkinson's disease were bisected; the resultant 10 samples were subjected to the JP content uniformity tests. We found that acceptance values of L-DOPA and BNS were 11.0-21.9% and 13.3-17.5%, respectively, with some non-conformity to the maximum allowed acceptance value (15.0%) as per the current JP. Image analyses by near IR showed that L-DOPA, BNS, lactose, and corn starch were uniformly distributed in each tablet; moreover, LF Raman spectroscopy imaging also supported the result that L-DOPA, BNS, and lactose were evenly distributed. Therefore, drug content in the tablets was uniform; thus, careful manipulation was recommended in the tablet bisection. However, the results of bisection line specifications and hardness tests revealed that the ease of division differed depending on the tablets, which warrants attention.

Comparison of various pharmaceutical properties of clobetasol propionate cream formulations - considering stability of mixture with moisturizer.
Yoshihisa Yamamoto; Yoshinori Onuki; Toshiro Fukami; Tatsuo Koide
Journal of pharmaceutical health care and sciences, 2020
BACKGROUND: The clobetasol propionate cream formulations (CLB Cr ) belong to the "strongest" group, and are used widely. In addition, those formulations are often used as a mixture with moisturizer. Recently, we evaluated pharmaceutical properties of the CLB Cr using near infrared (NIR) spectroscopy, and characteristic NIR spectra depending on the formulation were observed. In the present study, we attempted to evaluate the more diverse pharmaceutical properties of CLB Cr , including the stability of mixture of CLB Cr and moisturizer. METHOD: Pharmaceutical properties of CLB Cr were evaluated using from rheological characteristics, microscopic observation, dye permeability observations, electrical conductivity method, thermogravimetry-differential thermal analysis (TG-DTA) and near infrared (NIR) spectroscopy. Stability of mixtures of CLB Cr and moisturizer were evaluated using from dye method and NIR spectroscopy. RESULTS: The hardness of Dermovate® (DRM), Glydil® (GDL), and Myalone® (MYA) was greater than that of CLB Cr . High concentrations of white beeswax were considered the reason for the hardness of DRM and GDL. On the other hand, the hardness of MYA may be due to the presence of macrogol 6000. After storage of the cream formulations discharged from the tube at room temperature, mass reduction and attenuation of the peak reflecting water of NIR spectroscopy occurred in a time-dependent manner, except for GDL and MYA. Only GDL was shown to be a w/o-type formulation by dye and electric conductivity measurements, which suggested that this was the reason for the lack of changes in the mass or NIR spectrum of samples after storage. In the NIR spectrum of MYA, the peak reflecting water slightly increased in a time-dependent manner, suggesting the water absorption of macrogol 6000. TG-DTA provided curves indicating the presence of water in each formulation, except for MYA, which was consistent with water quantification previously reported. Finally, when mixing the CLB Cr with a moisturizer, in any CLB Cr , the stability of the mixture with w/o-type moisturizer varies greatly depending on the each CLB Cr . CONCLUSION: Thus, even for cream formulations with the same active pharmaceutical ingredient, pharmaceutical properties and stability of mixture with moisturizer may different significantly.

Imaging Analysis Enables Differentiation of the Distribution of Pharmaceutical Ingredients in Tacrolimus Ointments.
Mika Yoshimura Fujii; Yoshihisa Yamamoto; Tatsuo Koide; Masashi Hamaguchi; Yoshinori Onuki; Naoto Suzuki; Toyofumi Suzuki; Toshiro Fukami
Applied spectroscopy, Oct. 2019
We demonstrated the difference in the distribution state of pharmaceutical ingredients between tacrolimus (TCR) original ointment and six kinds of generic medicines. Two-dimensional imaging and depth analysis using attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy and confocal Raman microscopy were used, in addition to the evaluation of pharmaceutical properties, including spreading properties, rheological properties, and amount of solvent. The solvents, such as propylene carbonate and triacetin, in TCR ointments formed liquid droplets and dispersed in hydrocarbon oils. Waxes, white beeswax and beeswax, formed other domains. Confocal Raman microscopy could detect liquid droplet size without coalescence of that on germanium or glass surfaces. The combination of ATR FT-IR and confocal Raman imaging would be a powerful tool to reveal the size and shape of liquid droplets of pharmaceutical ingredients in semisolid formulations.

Evaluation of the three-dimensional distribution of droplets in a droplet dispersion-type ointment using confocal Raman microscopy
Yoshihisa Yamamoto; Mika Yoshimura Fujii; Toshiro Fukami; Tatsuo Koide
Journal of Drug Delivery Science and Technology, Jun. 2019

Optimum volume of water needed for the paste state of pediatric powders: Considerations based on yield values and applications to generic medicine
Haruka Fukuda; Toyofumi Suzuki; Kaname Hashizaki; Sayaka Yoshimura; Chika Kobayashi; Yosiko Omotani; Naoto Suzuki; Takanori Kanazawa; Toshiro Fukami; Yoshihisa Yamamoto
Yakugaku Zasshi, 2019, [Reviewed]

Evaluation of the Water Content and Skin Permeability of Active Pharmaceutical Ingredients in Ketoprofen Poultice Formulations Removed from Their Airtight Containers and Left at Room Temperature.
Yoshihisa Yamamoto; Rie Yamauchi; Shuji Ohno; Kazunori Asai; Toshiro Fukami; Tatsuo Koide
Biological & pharmaceutical bulletin, 2019
The poultice formulation is a patch containing a large amount of water. It is known that the water contained in the adhesive polymer layer (ADPL) of poultice affects the cooling sensation and skin permeability of the active pharmaceutical ingredient (API). In this study, we evaluated the relationship between the water content in a ketoprofen poultice formulation and the amount of time the poultice was left out at room temperature after removal from the airtight container, as well as the influence of the decreasing water content on the skin permeability of the API. After removing the poultice from the container for 1 h, the mass of the ADPL decreased by approximately 40%. When the near-infrared (NIR) spectrum of the ADPL of poultice was measured, the peaks reflecting the hydroxyl group were attenuated depending on the time left out at room temperature. It is suggested that the changes in the mass and NIR spectrum of the ADPL are caused by the change in the water content. Moreover, when the permeability of API was evaluated on hairless mouse skin, the cumulative skin permeation amount and flux decreased, while the lag time was prolonged as the time left out increased. These results suggest that the skin permeability of the API is impaired by water evaporation and that maintaining the water in the ADPL in poultice is very important from not only the viewpoint of cooling sensation, tackiness and moisturizing but also the skin permeability of the API.

Mixtures of betamethasone butyrate propionate ointments and heparinoid oil-based cream: Physical stability evaluation.
Yoshihisa Yamamoto; Akane Hanai; Yoshinori Onuki; Mika Fujii; Yu Onishi; Toshiro Fukami; Koichi Metori; Naoto Suzuki; Toyofumi Suzuki; Tatsuo Koide
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 01 Nov. 2018
Betamethasone butyrate propionate ointment (BBPO) is mainly used for adult patients in dermatology and is often prescribed as a mixture containing a base or moisturizing cream for various reasons. However, in the case of a moisturizing cream, since this formulation is composed of various ingredients, a physical change is expected to occur by mixing it with an ointment. Therefore, in the present study, the physical stability of a mixture of four BBPO formulations and heparinoid oily cream (HPOC) was examined. Layer separation was observed in all mixtures following centrifugation. The near-infrared (NIR) measurement showed a peak at 5200 cm-1 on the lower layer side, which strongly suggests the presence of water. The peak at 5200 cm-1 in the middle layer was hardly observed in the mixtures of two BBPO generic formulations and HPOC, thus suggesting that the separation was more advanced in those mixtures than in the others. These two mixtures separated into a semisolid layer (upper side) and a liquid layer (lower side) after 3 h of storage at 37 °C. The NIR measurement of each layer revealed that most of the semisolid layer was oil while the liquid layer was water. Furthermore, backscattered light measurements were conducted to monitor the behavior of the mixture's layer separation. An evaluation using model formulations revealed that the layer separation of the mixtures was due to the propylene glycol (PG) and surfactant content of the two generic BBPO formulations. Thus, these findings suggest that excipients need to be considered in selecting formulations for mixtures of skin preparations.

Molecular State of Active Pharmaceutical Ingredients in Ketoprofen Dermal Patches Characterized by Pharmaceutical Evaluation.
Motoshige Azuma; Mika Fujii; Motoki Inoue; Hiroshi Hisada; Tatsuo Koide; Mark Kemper; Yoshihisa Yamamoto; Naoto Suzuki; Toyofumi Suzuki; Toshiro Fukami
Biological & pharmaceutical bulletin, 2018
The molecular states of ketoprofen and the interaction between ketoprofen and other pharmaceutical excipients in the matrix layer were examined to determine their effect on the pharmaceutical properties of original and generic ketoprofen dermal patches (generic patches A and B). Molecular states of ketoprofen were evaluated using polarized light microscopy, Raman spectroscopy and powder X-ray diffraction. For the original ketoprofen patch, crystalline components were not observed in the matrix layer. However, crystalline ketoprofen was observed in the two generic ketoprofen patches. Moreover, the ketoprofen exhibited hydrogen bonding with the pharmaceutical excipients or patch materials in the generic products. Skin permeation of ketoprofen from the patches was evaluated using hairless mouse skin. Twelve hours after application, the original patch demonstrated the highest level of cumulative skin permeation of ketoprofen. This was followed by generic patch B while generic patch A showed the lowest level of permeation. Fluxes were calculated from the skin permeation profiles. The original patch was approx. 2.4-times faster compared with generic patch A and approximately 1.9-times faster compared with generic patch B. This investigation suggested that pharmaceutical properties such as skin permeability for these types of products are affected by the precipitation of crystalline ketoprofen in the matrix layer and the interaction of ketoprofen with the pharmaceutical excipients or patch materials.

Comparison of pharmaceutical properties among clobetasol propionate cream formulations: Considerations from near infrared spectra
Yoshihisa Yamamoto; Toshiro Fukami; Yoshinori Onuki; Koichi Metori; Toyofumi Suzuki; Tatsuo Koide
Vibrational Spectroscopy, Nov. 2017

Stability of Mixed Preparations Consisting of Commercial Moisturizing Creams with an Ointment Base Investigated by Magnetic Resonance Imaging.
Yoshinori Onuki; Chiaki Funatani; Yoshihisa Yamamoto; Toshiro Fukami; Tatsuo Koide; Yoshihiro Hayashi; Kozo Takayama
Chemical & pharmaceutical bulletin, 2017
A moisturizing cream mixed with a steroid ointment is frequently prescribed to patients suffering from atopic dermatitis. However, there is a concern that the mixing operation causes destabilization. The present study was performed to investigate the stability of such preparations closely using magnetic resonance imaging (MRI). As sample preparations, five commercial moisturizing creams that are popular in Japan were mixed with an ointment base, a white petrolatum, at a volume ratio of 1 : 1. The mixed preparations were stored at 60°C to accelerate the destabilization processes. Subsequently, the phase separations induced by the storage test were monitored using MRI. Using advanced MR technologies including spin-spin relaxation time (T2) mapping and MR spectroscopy, we successfully characterized the phase-separation behavior of the test samples. For most samples, phase separations developed by the bleeding of liquid oil components. From a sample consisting of an oil-in-water-type cream, Urepearl Cream 10%, a distinct phase-separation mode was observed, which was initiated by the aqueous component separating from the bottom part of the sample. The resultant phase separation was the most distinct among the test samples. To investigate the phase separation quantitatively and objectively, we conducted a histogram analysis on the acquired T2 maps. The water-in-oil type creams were found to be much more stable after mixing with ointment base than those of oil-in-water type creams. This finding strongly supported the validity of the mixing operation traditionally conducted in pharmacies.

Analysis of the Stability of External-Application Dermatologic Preparations: Consideration from Rheological Measurements.
Yoshihisa Yamamoto; Moemi Kumetani; Yoshinori Onuki; Tatsuo Koide; Toyofumi Suzuki; Toshiro Fukami
Chemical & pharmaceutical bulletin, 01 Jul. 2016
The present study examined the stability of mixtures of various combinations of moisturizers, water in oil (w/o)-type or oil in water (o/w)-type cream preparations containing heparinoids, and steroidal ointments or creams (o/w-type) frequently used in children. Centrifugation at room temperature led to separation of mixtures of w/o-type moisturizers and steroidal ointments into three layers. Polarized microscopic observations, near-infrared (NIR) spectroscopy, and dye-based analyses revealed the presence of oily components in the upper and middle layers and water-soluble components in the lower layer. Separation into three layers upon centrifugation was also observed for mixtures of o/w-type moisturizers and steroidal ointments. In contrast, neither the o/w-type moisturizer and steroidal cream nor the w/o-type moisturizer and steroidal cream mixtures separated into layers upon centrifugation. Consideration of the characteristics of each preparation is necessary when mixing external-application dermatologic preparations. Centrifugation at 4°C did not result in layer separation of the w/o-type moisturizer and steroidal ointment mixture, suggesting that cold storage of such mixtures provides superior stability compared with room temperature storage. However, despite no obvious layer separation, the NIR spectra indicated that water movement was induced within the mixture. These results clearly indicate that methods such as NIR spectroscopy are useful for early determinations of the stability of mixed external-application dermatologic preparations.

Pharmaceutical evaluation of atorvastatin calcium tablets available on the Internet: A preliminary investigation of substandard medicines in Japan
Toshiro Fukami; Tatsuo Koide; Hiroshi Hisada; Motoki Inoue; Yoshihisa Yamamoto; Toyofumi Suzuki; Kazuo Tomono
Journal of Drug Delivery Science and Technology, Feb. 2016

Studies on uniformity of the active ingredients in acetaminophen suppositories re-solidified after melting under high temperature conditions.
Yoshihisa Yamamoto; Toshiro Fukami; Tatsuo Koide; Yoshinori Onuki; Toyofumi Suzuki; Noriko Katori; Kazuo Tomono
Chemical & pharmaceutical bulletin, 2015
The target of the present pharmaceutical study was the antipyretic analgesic, acetaminophen; its suppository form is usually split when used in pediatric patients. We focused on the active ingredient uniformity in these products, which were re-solidified after melting under high temperature condition. When sections of the cut surfaces of the seven acetaminophen suppository products (SUP-A-G) commercially available in Japan were visualized by polarized microscopy, acetaminophen crystals that were dispersed in the base were identified. The results of the quantitative determination of agent concentration for each cut portion (mg/g) suggested uniform dispersion of these crystals in the base of each product. The agent concentration in each portion of the suppositories that was re-solidified after melting at high temperatures was measured. Segregation of the active ingredient was observed in four products at a temperature of 40°C for 1 h, while active ingredient uniformity was maintained in the other three products (SUP-C, SUP-F and SUP-G). The latter three products also showed high viscosity at 40°C. At 50°C for 4 h, only the uniformity of the active ingredient in SUP-C was maintained. These results suggest that the uniformity of the active ingredient is lost in some acetaminophen suppositories that were re-solidified after melting under high temperature conditions. The degree of loss varies depending on the product.

Analysis of Distribution of Ingredients in Commercially Available Clarithromycin Tablets Using Near-Infrared Chemical Imaging with Principal Component Analysis and Partial Least Squares.
Tatsuo Koide; Yoshihisa Yamamoto; Toshiro Fukami; Noriko Katori; Haruhiro Okuda; Yukio Hiyama
Chemical & pharmaceutical bulletin, 2015
The aim of this study was to evaluate pharmaceuticals using a near-infrared chemical imaging (NIR-CI) technique for visualizing the distribution of ingredients in solid dosage forms of commercially available clarithromycin tablets. The cross section of a tablet was measured using the NIR-CI system for evaluating the distribution of ingredients in the tablet. The chemical images were generated by performing multivariate analysis methods: principal component analysis (PCA) and partial least squares (PLS) with normalized near-infrared (NIR) spectral data. We gained spectral and distributional information related to clarithromycin, cornstarch, and magnesium stearate by using PCA analysis. On the basis of this information, the distribution images of these ingredients were generated using PLS analysis. The results of PCA analysis enabled us to analyze individual components by using PLS even if sufficient information on the products was not available. However, some ingredients such as binder could not be detected using NIR-CI, because their particle sizes were smaller than the pixel size (approximately 25×25×50 µm) and they were present in low concentrations. The combined analysis using both PCA and PLS with NIR-CI was useful to analyze the distribution of ingredients in a commercially available pharmaceutical even when sufficient information on the product is not available.

Magnetic resonance imaging of the phase separation in mixed preparations of moisturizing cream and steroid ointment after centrifugation.
Yoshinori Onuki; Chiaki Funatani; Takashi Yokawa; Yoshihisa Yamamoto; Toshiro Fukami; Tatsuo Koide; Yasuko Obata; Kozo Takayama
Chemical & pharmaceutical bulletin, 2015
A mixed preparation consisting of a water-in-oil emulsion-type moisturizing cream and a steroid ointment is frequently prescribed for the treatment of atopic dermatitis. We have investigated the compatibility of moisturizing creams and ointments because there are concerns regarding the physical stability of these mixed preparations. The key technology used in this study was magnetic resonance imaging (MRI). A commercial moisturizing cream and white petrolatum or clobetasone butyrate (CLB) ointment samples were mixed in a weight ratio of 1 : 1. A centrifugation test protocol (20000×g for 3 min) was implemented to accelerate the destabilization processes in the samples. After centrifugation, the mixed preparations separated into three distinct layers (upper, middle, and lower), while no phase separation was observed using moisturizing cream alone. The phase separation was monitored using chemical shift selective images of water and oil and quantitative T2 maps. In addition, MR and near-infrared spectroscopy were employed for component analysis of each phase-separated layer. Collectively, it was confirmed that the lower layer contained water, oils, and organic solvent, while the upper and middle layers were composed solely of oils. Furthermore, this study investigated the distribution of CLB in the phase-separated samples and showed that a heterogeneous distribution existed. From our results, it was confirmed that the mixed preparation became unstable because of the incompatibility of the moisturizing cream and ointment.

Comparative pharmaceutical evaluation of brand and generic clobetasone butyrate ointments.
Yoshihisa Yamamoto; Toshiro Fukami; Tatsuo Koide; Yoshinori Onuki; Toyofumi Suzuki; Koichi Metori; Noriko Katori; Yukio Hiyama; Kazuo Tomono
International journal of pharmaceutics, 10 Mar. 2014
In the present study, we performed comprehensive pharmaceutical evaluation among an original clobetasone butyrate (CLB) ointment product and three generic products. Although spherocrystal images were observed under a polarizing microscope for only Kindavate®, the original product, distribution of active and inactive ingredients was chemically equivalent between the original and generic medicine by the attenuated total reflection infrared spectroscopy. These results suggest that the spherocrystals observed in Kindavate® are composed of hydrocarbon. On GC/MS, it was revealed that linear alkanes having 25-27 carbon atoms are densely present in Sun White®, the base used in Kindavate®. On the other hand, linear alkanes having 22-31 carbon atoms were broadly distributed in most other white petrolatums. In the CLB ointment products, the distribution equivalent of linear alkane to Sun White® was observed only in Kindavate®. Thus, the GC/MS method is extremely useful for identification of white petrolatum used in the ointment. A similar amount of CLB among the pharmaceutical products was detected in the skin tissue by skin accumulation test, although there were the differences in rheological properties and the quality of white petrolatum. The present results will be very useful for pharmacists in selecting medicine products that match the needs of the patient. Such pharmaceutical information will help spread objective knowledge about products in the future, and will contribute to the appropriate selection of medication.

Pharmaceutical evaluation of steroidal ointments by ATR-IR chemical imaging: distribution of active and inactive pharmaceutical ingredients.
Yoshihisa Yamamoto; Toshiro Fukami; Tatsuo Koide; Toyofumi Suzuki; Yukio Hiyama; Kazuo Tomono
International journal of pharmaceutics, 15 Apr. 2012
We recently used micro attenuated total reflection infrared (ATR-IR) spectroscopy to conduct imaging analysis of ointments and evaluate the distributions of the active pharmaceutical ingredient (API) and excipients. An alclometasone dipropionate (ALC) ointment was used as a model product. Almeta, a brand-name product, had a domain with absorbance at 1656 cm(-1) attributable to the carbonyl group of ALC, the API. Absorbances at 1040 and 3300 cm(-1) were also noted in this domain, indicating the presence of the solubilizer, propylene glycol. Data also suggested the presence of benzyl alcohol in this domain. More detailed analysis showed the distribution of surfactants and other excipients in the base. Similar results were obtained for Vitra, a generic version of Almeta. Imaging analysis with micro ATR-IR confirmed that both ointments are liquid droplet dispersions with ALC dissolved in propylene glycol and dispersed in a base. However, minor differences in the ingredient distributions of the two ointments were detected and reflect differences in excipient concentrations and type, or manufacturing differences. In summary, we used micro ATR-IR for imaging analysis of an original ointment, Almeta, and its generic form Vitra, and established a method for visually evaluating the distributions of the API and excipients in these ointments.

ステロイド軟膏製剤のレオロジー特性に関する評価～後発品および保湿剤との混合製剤における展延性～　　　　　　　　　　　　　　　
2012, [Reviewed]

Evaluation of the degree of mixing of combinations of dry syrup, powder, and fine granule products in consideration of particle size distribution using near infrared spectrometry.
Yoshihisa Yamamoto; Toyofumi Suzuki; Mika Matsumoto; Michiteru Ohtani; Shuichi Hayano; Toshiro Fukami; Kazuo Tomono
Chemical & pharmaceutical bulletin, 2012
We used near infrared (NIR) spectroscopy to evaluate the degree of mixing of blended dry syrup (DS) products whose particle sizes are not specified in the Revised 16th Edition of the Japanese Pharmacopoeia, and also evaluated the degree of mixing when powder products or fine granule products were added to DS products. The data obtained were used to investigate the relationship between the particle size distributions of the products studied and the degree of mixing. We found that the particle size distribution characteristics of the 15 DS products studied can be broadly classified into 5 types. Combinations of frequently prescribed products were selected to represent 4 of the 5 particle size distribution types and were blended with a mortar and pestle. The coefficient of variation (CV) decreased as the percent mass of Asverin® Dry Syrup 2% (Asverin-DS) increased in blends of Periactin® Powder 1% (Periactin) and Asverin-DS, indicating an improved degree of mixing (uniformity). In contrast, in blends of Periactin and Mucodyne® DS 33.3%, mixing a combination at a 1:1 mass ratio 40 times resulted in a CV of 20%. Other mixing frequencies and mass ratios resulted in a CV by 50% to 70%, indicating a very poor degree of mixing (poor uniformity). These results suggest that when combining different DSs, or a DS with a powder or fine granule product, the blending obtained with a mortar and pestle improves as the particle size distributions of the components approach each other and as the ranges of the distributions narrow.

Adhesion Loss of Syrups in a Metering Glass Which Consists of a Low Surface Free Energy Material
Yoshihisa Yamamoto; Toyofumi Suzuki; Kaname Hashizaki; Masao Ogura; Yukiko Umeda; Shinji Hidaka; Toshiro Fukami; Kazuo Tomono
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, Aug. 2010, [Reviewed]

Quantitative Relationship between Adhesion Loss of Syrups for Infants in a Metering Glass and Their Rheological Characteristics
Yoshihisa Yamamoto; Toyofumi Suzuki; Toshiro Fukami; Mamoru Kamano; Kazuo Tomono
Jpn. J. Pharm. Health Care Sci., Jul. 2008, [Reviewed]
We determined the adhesion loss in a metering glass for 9 types of syrup for infants, and investigated the relationship between the adhesion loss and the rheological properties of the syrups. There was a good correlation (r^2=0.981) between the viscosity of the syrups and percentage syrup residues on the metering glass. Further, from the viewpoints of accuracy and efficiency in dispensing, our finding that percentage residues for a dispenser were much lower (<0.15%) than for the metering glass suggested that it was better to use a dispenser for dispensing viscous syrups with a viscosity of at least 50-60 mPa・s. The results of our examination of syrup viscosities in the present study are expected to be useful information for their administration, and to contribute to the establishment of dispensing procedures based on scientific evidence.

Simplified means of evaluating drug concentrations in patients' blood using Microsoft Excel at a community pharmacy
Yoshihisa Yamamoto; Toyofumi Suzuki; Toshiro Fukami; Mamoru Kamanta; Kazuo Tomono
Japanease Journal of Pharmaceutical Health Care and Sciences, Jun. 2007, [Reviewed]
Using Microsoft Excel^[○!R], we explained in simple terms how the times of taking drugs are determined to patients at a pharmacy counter, in the case of medicines for children. We highlighted the change in drug concentrations with time using pharmacokinetics parameters, such as time of peak concentration, half-life, and area under the blood concentration-time curve, whose values were indicated in the interview-form. Prediction of the blood drug concentration curve was based on the one-compartment absorption model. We found that various drugs, such as aciclovir (Astric^[○!R] dry syrup), oseltamivir phosphate (Tamiflu^[○!R] dry syrup), clarithromycin (Clarith^[○!R] dry syrup), cefditoren pivoxil (Meiact MS^[○!R] fine granules), oxatomide (Celtect^[○!R] dry syrup) and procaterol hydrochloride (Meptin^[○!R] dry syrup), had characteristic concentration patterns that could be understood visually. We also noted that the indices provided by our simple evaluation using Microsoft Excel^[○!R] enabled drug concentrations in blood-time profiles to be compared visually in the case of patients complying with medication schedules and those not complying e.g. in the case that schedules are modified, the patient misses taking medicine or takes more than 1 dose at once. It was also possible to examine the relationship between the predicted blood concentration patterns of drugs and their efficacy or safety for each medicine. This technique would be useful means of helping pharmacists to fully realize their role in the community pharmacy.

Quality Testing of Steroidal Ointment Mixed with White Petrolatum: Rheological Property and Stability Test
Jpn. J. Pharm. Health Care Sci., Sep. 2006, [Reviewed]

乳幼児の散剤服用法についての検討 少量の水で練る場合の至適水分量について
Aug. 2005, [Reviewed]

Characterization of α1-adrenoceptor-mediated contraction in the mouse thoracic aorta
Yoshihisa Yamamoto; Katsuo Koike
European Journal of Pharmacology, Jul. 2001, [Reviewed]

α1-Adrenoceptor subtypes in the mouse mesenteric artery and abdominal aorta　　　　　　　　　　　　　　　
Br. J. Pharmacol., 2001, [Reviewed]

The Effects of β-Adrenoceptor Agonists on KCl-induced Rhythmic Contraction in the Ureter of Guinea Pig.
Yoshihisa YAMAMOTO; Katsuo KOIKE
Journal of Smooth Muscle Research, 2000

α1-Adrenoceptors in the Guinea Pig Thoracic Aorta
Yoshihisa YAMAMOTO; Katsuo KOIKE
Journal of Smooth Muscle Research, 1999

β-Adrenoceptors in the Detrusor of Guinea Pig Bladder.
Yoshihisa YAMAMOTO; Akari MORI; Katsuo KOIKE
Journal of Smooth Muscle Research, 1998, [Reviewed]

Characterization of endothelin receptor subtypes mediating Ca²⁺mobilization and contractile response in rabbit iris dilator muscle
Mitsutoshi Satoh; Yoshihisa Yamamoto; Issei Takayanagi
British Journal of Pharmacology, Mar. 1996

Pre- and postjunctional actions of endothelin in the rat iris sphincter preparation　　　　　　　　　　　　　　　
Naunyn-Schmiedeberg`s Arch. Pharmacol., 350: 63-7 (1994), 1994, [Reviewed]

（解説記事）特集 知ってるつもりの製剤ナレッジ 製剤学的な観点からの薬学的管理 一包化　　　　　　　　　　　　　　　
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（記事）薬剤師が業務に活かすことのできる製剤物性情報について考える～薬局薬剤師時代の経験を踏まえて～　　　　　　　　　　　　　　　
Oct. 2024

（解説記事）Clinical Questionに基づく製剤研究の発展を目指して　　　　　　　　　　　　　　　
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（解説記事）坐剤を分割するときの注意点は？　　　　　　　　　　　　　　　
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（解説記事）坐剤に使われている基剤とその注意点は？　　　　　　　　　　　　　　　
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（解説記事）一度融けた坐剤は，固まれば使っていいの？　　　　　　　　　　　　　　　
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（解説記事）軟膏やクリーム剤を混合する際の注意点は？　　　　　　　　　　　　　　　
2024

（解説記事）そもそもシロップ剤って混ぜてしまっていいの？　　　　　　　　　　　　　　　
2024

（解説記事）ステロイド外用剤と保湿剤の希釈・混合可否を判定する　　　　　　　　　　　　　　　
Jul. 2022

（解説記事）ジアゼパム坐剤２回目投与のタイミングを指導する　　　　　　　　　　　　　　　
Jul. 2022

（解説記事）坐剤の保管方法を指導する　　　　　　　　　　　　　　　
Jul. 2022

（解説記事）同時に２種類以上の坐剤を使用するときの注意点を伝える　　　　　　　　　　　　　　　
Jul. 2022

（解説記事）１日３回服用する薬のアドヒアランスを改善する　　　　　　　　　　　　　　　
Jul. 2022

（解説記事）－特集にあたって－薬剤学で強化する！子どもの調剤・服薬指導　　　　　　　　　　　　　　　
Jul. 2022

（解説記事）STOP! 計算エラー「小児薬用量」おさらいドリル　　　　　　　　　　　　　　　
Jul. 2022

（解説記事）軟膏などの半固形製剤の混合と重ね塗り，特徴と使い分けは？　　　　　　　　　　　　　　　
Jun. 2022

（解説記事）便秘薬の剤形・用法と使い分け　　　　　　　　　　　　　　　
Apr. 2022

（解説記事）半固形製剤における分光学的手法による製剤学的評価～医療従事者が利用する情報としての有用性～　　　　　　　　　　　　　　　
Feb. 2022

（解説記事）外用剤混合におけるジェネリック医薬品使用の問題点　　　　　　　　　　　　　　　
Oct. 2021

（解説記事）各種薬剤の調製・取り扱いに関するトピックスー外用剤ー　　　　　　　　　　　　　　　
Feb. 2020

（解説記事）分光学的手法を用いた皮膚外用製剤の評価（II）－ベタメタゾン酪酸エステルプロピオン酸エステル軟膏の製剤特性およびヘパリン類似物質油性クリームとの混合物安定性評価ー　　　　　　　　　　　　　　　
Jun. 2019

（解説記事）分光学的手法を用いた皮膚外用製剤の評価（I）－近赤外分光法によるクロベタゾールプロピオン酸エステルクリーム剤の製剤学的評価ー　　　　　　　　　　　　　　　
Mar. 2019

（記事）研究室紹介〜調剤現場で発生する問題点を薬剤学的に検証する〜　　　　　　　　　　　　　　　
Jan. 2017

（解説記事）粉薬をペースト状にするにはどのくらいの水分量が必要？　　　　　　　　　　　　　　　
Nov. 2016

（解説記事）坐剤に関するFAQ　　　　　　　　　　　　　　　
Oct. 2016

（解説記事）クロベタゾン酪酸エステル軟膏の製剤学的評価ー先発品とジェネリック品との比較ー　　　　　　　　　　　　　　　
Feb. 2014

（記事）調剤現場から見えた薬剤学　　　　　　　　　　　　　　　
Sep. 2013

（解説記事）液滴分散型軟膏の顕微ATR-IRイメージング　　　　　　　　　　　　　　　
Jun. 2013

（解説記事）小児の散剤服用法‐散剤をペースト状にするための至適水分量と服薬指導への活用‐　　　　　　　　　　　　　　　
Apr. 2006

Crosslink Pharmaceutical Textbook: Pharmaceutics　　　　　　　　　　　　　　　
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調剤と服薬指導がわかる 小児科これだけ　　　　　　　　　　　　　　　
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薬語図鑑　　　　　　　　　　　　　　　
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基礎と臨床をつなぐ 物理薬剤学・製剤学　　　　　　　　　　　　　　　
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マイスターから学ぶ皮膚科治療薬の服薬指導術　　　　　　　　　　　　　　　
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エマルションの特性評価と新製品開発，品質管理への活用　　　　　　　　　　　　　　　
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