Publications by authors named "Yukio Hiyama"

12 Publications

  • Page 1 of 1

Analysis of Distribution of Ingredients in Commercially Available Clarithromycin Tablets Using Near-Infrared Chemical Imaging with Principal Component Analysis and Partial Least Squares.

Chem Pharm Bull (Tokyo) 2015 ;63(9):663-8

Division of Drugs, National Institute of Health Sciences.

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.
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http://dx.doi.org/10.1248/cpb.c14-00811DOI Listing
June 2016

Comparative pharmaceutical evaluation of brand and generic clobetasone butyrate ointments.

Int J Pharm 2014 Mar 7;463(1):62-7. Epub 2014 Jan 7.

School of Pharmacy, Nihon University, Japan.

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.
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http://dx.doi.org/10.1016/j.ijpharm.2013.12.054DOI Listing
March 2014

Detection of component segregation in granules manufactured by high shear granulation with over-granulation conditions using near-infrared chemical imaging.

Int J Pharm 2013 Jan 12;441(1-2):135-45. Epub 2012 Dec 12.

Division of Drugs, National Institute of Health Sciences, 1-18-1 Kamiyoga, Tokyo 158-8501, Japan.

The objective of this study was to evaluate the high shear granulation process using near-infrared (NIR) chemical imaging technique and to make the findings available for pharmaceutical development. We prepared granules and tablets made under appropriate- and over-granulation conditions with high shear granulation and observed these granules and tablets using NIR chemical imaging system. We found an interesting phenomenon: lactose agglomeration and segregation of ingredients occurred in experimental tablets when over-granulation conditions, including greater impeller rotation speeds and longer granulation times, were employed. Granules prepared using over-granulation conditions were larger and had progressed to the consolidation stage; segregation between ethenzamide and lactose occurred within larger granules. The segregation observed here is not detectable using conventional analytical technologies such as high pressure liquid chromatography (HPLC) because the content of the granules remained uniform despite the segregation. Therefore, granule visualization using NIR chemical imaging is an effective method for investigating and evaluating the granulation process.
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http://dx.doi.org/10.1016/j.ijpharm.2012.12.005DOI Listing
January 2013

Non-destructive analysis of tulobuterol crystal reservoir-type transdermal tapes using near infrared spectroscopy and imaging.

J Pharm Biomed Anal 2013 Feb 16;74:14-21. Epub 2012 Oct 16.

Division of Drugs, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.

A non-destructive method for analyzing crystalline tulobuterol (TBR; a bronchodilator [β(2)-blocker]) in transdermal drug delivery system tapes with a crystal reservoir system was developed. A near infrared spectroscopy (NIRS) and a near infrared spectroscopic imaging (NIRI) were used to investigate the distribution of TBR crystals in transdermal tapes. The characteristic peak derived from a first overtone of secondary amine which appears based on crystal growth was used for the detection of crystals. NIR images were composed by the integrated values of that peak at each pixel. The time-course analysis by NIRS showed that the intensity of the peaks gradually increased, and the intensity reached a plateau between day 30 and day 42 after preparation of the model tapes. The authors observed the growth and distribution of TBR crystals in small areas in several types of matrices by NIRI time-course measurement. The authors also found that a macroscopic map can provide a rough distribution map of crystalline TBR in a whole matrix. In the case in which a tape distributed from the innovator was examined, the characteristic peak was also detected through a liner or a supporting board, by transmittance-reflectance NIR measurement.
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http://dx.doi.org/10.1016/j.jpba.2012.10.003DOI Listing
February 2013

Coating and Density Distribution Analysis of Commercial Ciprofloxacin Hydrochloride Monohydrate Tablets by Terahertz Pulsed Spectroscopy and Imaging.

J Pharm Innov 2012 Jun 25;7(2):87-93. Epub 2012 May 25.

Terahertz pulsed spectroscopy was used to qualitatively detect ciprofloxacin hydrochloride monohydrate (CPFX·HCl·H(2)O) in tablets, and terahertz pulsed imaging (TPI) was used to scrutinize not only the coating state but also the density distribution of tablets produced by several manufacturers. TPI was also used to evaluate distinguishability among these tablets. The same waveform, which is a unique terahertz absorption spectrum derived from pure CPFX·HCl·H(2)O, was observed in all of the crushed tablets and in pure CPFX·HCl·H(2)O. TPI can provide information about the physical states of coated tablets. Information about the uniformity of parameters such as a coating thickness and density can be obtained. In this study, the authors investigated the coating thickness distributions of film-coated CPFX·HCl·H(2)O from four different manufacturers. Unique terahertz images of the density distributions in these commercial tablets were obtained. Moreover, B-scan (depth) images show the status of the coating layer in each tablet and the density map inside the tablets. These features would reflect differences resulting from different tablet-manufacturing processes.
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http://dx.doi.org/10.1007/s12247-012-9130-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366064PMC
June 2012

Pharmaceutical evaluation of steroidal ointments by ATR-IR chemical imaging: distribution of active and inactive pharmaceutical ingredients.

Int J Pharm 2012 Apr 20;426(1-2):54-60. Epub 2012 Jan 20.

Laboratory of Pharmaceutics, School of Pharmacy, Nihon University, Funabashi-shi, Chiba 274-8555, Japan.

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.
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http://dx.doi.org/10.1016/j.ijpharm.2012.01.017DOI Listing
April 2012

[Pharmaceutical product quality control and good manufacturing practices].

Authors:
Yukio Hiyama

Kokuritsu Iyakuhin Shokuhin Eisei Kenkyusho Hokoku 2010 (128):1-16

This report describes the roles of Good Manufacturing Practices (GMP) in pharmaceutical product quality control. There are three keys to pharmaceutical product quality control. They are specifications, thorough product characterization during development, and adherence to GMP as the ICH Q6A guideline on specifications provides the most important principles in its background section. Impacts of the revised Pharmaceutical Affairs Law (rPAL) which became effective in 2005 on product quality control are discussed. Progress of ICH discussion for Pharmaceutical Development (Q8), Quality Risk Management (Q9) and Pharmaceutical Quality System (Q10) are reviewed. In order to reconstruct GMP guidelines and GMP inspection system in the regulatory agencies under the new paradigm by rPAL and the ICH, a series of Health Science studies were conducted. For GMP guidelines, product GMP guideline, technology transfer guideline, laboratory control guideline and change control system guideline were written. For the GMP inspection system, inspection check list, inspection memo and inspection scenario were proposed also by the Health Science study groups. Because pharmaceutical products and their raw materials are manufactured and distributed internationally, collaborations with other national authorities are highly desired. In order to enhance the international collaborations, consistent establishment of GMP inspection quality system throughout Japan will be essential.
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May 2011

Near-infrared analysis of hydrogen-bonding in glass- and rubber-state amorphous saccharide solids.

AAPS PharmSciTech 2009 7;10(2):524-9. Epub 2009 May 7.

National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya, Tokyo, 158-8501, Japan.

Near-infrared (NIR) spectroscopic analysis of noncrystalline polyols and saccharides (e.g., glycerol, sorbitol, maltitol, glucose, sucrose, maltose) was performed at different temperatures (30-80 degrees C) to elucidate the effect of glass transition on molecular interaction. Transmission NIR spectra (4,000-12,000 cm(-1)) of the liquids and cooled-melt amorphous solids showed broad absorption bands that indicate random configuration of molecules. Heating of the samples decreased an intermolecular hydrogen-bonding OH vibration band intensity (6,200-6,500 cm(-1)) with a concomitant increase in a free and intramolecular hydrogen-bonding OH group band (6,600-7,100 cm(-1)). Large reduction of the intermolecular hydrogen-bonding band intensity at temperatures above the glass transition (T(g)) of the individual solids should explain the higher molecular mobility and lower viscosity in the rubber state. Mixing of the polyols with a high T(g) saccharide (maltose) or an inorganic salt (sodium tetraborate) shifted both the glass transition and the inflection point of the hydrogen-bonding band intensity to higher temperatures. The implications of these results for pharmaceutical formulation design and process monitoring (PAT) are discussed.
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http://dx.doi.org/10.1208/s12249-009-9243-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2690806PMC
June 2009

Interleukin-6 induces prostaglandin E(2) synthesis in mouse astrocytes.

J Mol Neurosci 2009 Sep 10;39(1-2):175-84. Epub 2009 Mar 10.

Department of Hygienic Chemistry, Showa Pharmaceutical University, Machida-shi, Tokyo 194-8543, Japan.

The physiological function of interleukin-6 within the central nervous system (CNS) is complex; interleukin-6 exerts neurotrophic and neuroprotective effects and yet can also function as a mediator of inflammation, demyelination, and astrogliosis depending on the cellular context. However, the roles of interleukin-6 in astrocytes are poorly understood. In the present study, we investigated the effect of the pro-inflammatory cytokine interleukin-6 on the production of the inflammatory mediator prostaglandin E(2) in mouse astrocytes. Interleukin-6 stimulated prostaglandin E(2) production in a time-dependent fashion via a rapid and transient induction of cyclooxygenase-2 messenger RNA, followed by cyclooxygenase-2 protein synthesis. Interleukin-6 may act on the nervous system by interacting with its specific soluble interleukin-6 receptor and the signal transducer 130-kDa glycoprotein. Simultaneous treatment of astrocytes with interleukin-6 and soluble interleukin-6 receptor caused marked induction of prostaglandin E(2) synthesis, and this effect was suppressed by adding a neutralizing antibody against soluble interleukin-6 receptor. Furthermore, the mouse 130-kDa glycoprotein antibody suppressed prostaglandin E(2) formation induced by interleukin-6, as well as interleukin-6/soluble interleukin-6 receptor complexes, in a dose-dependent manner. These results indicate that interleukin-6/soluble interleukin-6 receptor complexes and the signal transducer 130-kDa glycoprotein play an important role in the regulation of cyclooxygenase-2 expression and subsequent prostaglandin E(2) formation in mouse astrocytes and that interleukin-6 is an important regulator of immune and inflammatory processes in the CNS.
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http://dx.doi.org/10.1007/s12031-009-9187-6DOI Listing
September 2009

Monitoring minimization of grade B environments based on risk assessment using three-dimensional airflow measurements and computer simulation.

PDA J Pharm Sci Technol 2008 Jul-Aug;62(4):244-55

Pharmaceutical Research & Technology Laboratories, Astellas Pharmaceutical Inc., Shizuoka, Japan.

A practical, risk-based monitoring approach using the combined data collected from actual experiments and computer simulations was developed for the qualification of an EU GMP Annex 1 Grade B, ISO Class 7 area. This approach can locate and minimize the representative number of sampling points used for microbial contamination risk assessment. We conducted a case study on an aseptic clean room, newly constructed and specifically designed for the use of a restricted access barrier system (RABS). Hotspots were located using three-dimensional airflow analysis based on a previously published empirical measurement method, the three-dimensional airflow analysis. Local mean age of air (LMAA) values were calculated based on computer simulations. Comparable results were found using actual measurements and simulations, demonstrating the potential usefulness of such tools in estimating contamination risks based on the airflow characteristics of a clean room. Intensive microbial monitoring and particle monitoring at the Grade B environmental qualification stage, as well as three-dimensional airflow analysis, were also conducted to reveal contamination hotspots. We found representative hotspots were located at perforated panels covering the air exhausts where the major piston airflows collect in the Grade B room, as well as at any locations within the room that were identified as having stagnant air. However, we also found that the floor surface air around the exit airway of the RABS EU GMP Annex 1 Grade A, ISO Class 5 area was always remarkably clean, possibly due to the immediate sweep of the piston airflow, which prevents dispersed human microbes from falling in a Stokes-type manner on settling plates placed on the floor around the Grade A exit airway. In addition, this airflow is expected to be clean with a significantly low LMAA. Based on these observed results, we propose a simplified daily monitoring program to monitor microbial contamination in Grade B environments. To locate hotspots we propose using a combination of computer simulation, actual airflow measurements, and intensive environmental monitoring at the qualification stage. Thereafter, instead of particle or microbial air monitoring, we recommend the use of microbial surface monitoring at the main air exhaust. These measures would be sufficient to assure the efficiency of the monitoring program, as well as to minimize the number of surface sampling points used in environments surrounding a RABS.
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March 2009

Near-infrared analysis of protein secondary structure in aqueous solutions and freeze-dried solids.

J Pharm Sci 2006 Apr;95(4):781-9

National Institute of Health Sciences, Kamiyoga, Setagaya 158-8501, Tokyo, Japan.

Near-infrared spectroscopy (NIR) of various proteins (bovine serum albumin, lysozyme, ovalbumin, gamma-globulin, beta-lactoglobulin, myoglobin, cytochrome-c) was investigated as a possible analytical method of the protein secondary structure in various physical states. The spectra of proteins in aqueous solutions (transmission mode, solvent-compensated) and those in freeze-dried solids (nondestructive diffuse reflection mode) showed several bands at similar frequencies in the combination (4000-5000 cm(-1)) and first overtone (5600-6600 cm(-1)) spectral regions. The normalized second-derivative near-infrared spectra of proteins in aqueous solutions suggested that some bands indicated alpha-helix (4090, 4365-4370, 4615, and 5755 cm(-1)) and beta-sheet (4060, 4405, 4525-4540, 4865, and 5915-5925 cm(-1)) structures. The proteins mostly maintained spectra characteristic of their native structure after freeze-drying, although some reductions in alpha-helical structure and increase in unordered or beta-sheet structures were observed. The near-infrared analysis also showed beta-sheet formation of heat-treated BSA in aqueous solutions and in subsequently freeze-dried solids. The present results thus indicated that the nondestructive near-infrared analysis can be used for the investigation of dehydration-induced changes in protein secondary structures.
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http://dx.doi.org/10.1002/jps.20580DOI Listing
April 2006

Establishment of critical contamination risk locations ("hot spots") in environmental monitoring by means of three-dimensional airflow analysis and particulate evaluation.

PDA J Pharm Sci Technol 2005 Jan-Feb;59(1):49-63

Fujisawa Pharmaceutical Co, Ltd, Pharmaceutical Science Laboratories, Osaka, Japan.

A practical approach for the qualification of the surrounding environment of the critical area in aseptic processing has been developed. This method uses three-dimensional air velocity measurements combined with airborne particle monitoring. The analysis of the results obtained using the methods described in this article are beneficial in the selection of sample sites and frequencies and in refining personnel procedures and materials flow in aseptic processing. We propose that this improved qualification method can be widely applicable for both existing and new aseptic processing areas. This paper shows the results of one case study utilizing this method. The particle distribution map of a Grade B environment based upon extensive analysis was found to correspond to room airflow, as visualized by air vector mapping. The actual annual environmental monitoring data, which include airborne particles and microbes, as well as other microbial monitoring data, are also presented with respect to their relationship to the airflow pattern.
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April 2005
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