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Asian Journal of Pharmaceutical Sciences 2016年第4期11卷 479-485页

作者： Tamami Haraguchi Miyako Yoshida honami kojima Takahiro Uchida School of Pharmaceutical Science Mukogawa Women’s University

The purpose of this review is to discuss the advantages and limitations of taste sensors in the evaluation of the taste of palatability of different oral dosage forms. First, we consider some ways in which the palatability of various pharmaceutical formulations including orally disintegrating tablets(ODTs) are tested using two different taste sensors. Second, we focus on the evaluation of palatability of ODTs. We compare the usefulness of three pieces of apparatus for estimating the disintegration time of ODTs. Finally, we compare the characteristics of the two taste sensors in the evaluation of palatability of various kinds of drug formulations.

关键词： Palatability Taste sensor Orally disintegrating tablet (ODT) Disintegration time Drug formulation

Evaluating the Effects of Crystallinity on Drug Release Behaviour in Itraconazole- or Miconazole-Loaded PLGA Microparticles Prepared Using a Co-Grinding Method

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Pharmacology & Pharmacy 2023年第9期14卷 348-362页

作者： Kazuhiro Matsuura honami kojima Miyako Yoshida Takahiro Uchida Formulation Technology Research Laboratories Daiichi Sankyo Co. Ltd. Hiratsuka Japan Faculty of Pharmaceutical Science Mukogawa Women’s University Nishinomiya Japan

This study aimed to prepare and characterize itraconazole (ITCZ)- or miconazole (MCZ)-loaded poly (lactide-co-glycolide) (PLGA) microparticles (MP) using a co-grinding method with ball milling, which is a solvent-free and convenient procedure. PLGA MP was prepared by grinding for 60 min, and the fixed theoretical drug loading was set at 9.1% and 16.7% for both drugs. The obtained loading efficiency for both drugs was estimated to be approximately 100%. The average diameters of the drug-loaded PLGA MP were approximately 20 - 35 μm. Powder X-ray diffraction (PXRD) or differential scanning calorimetry (DSC) confirmed amorphization of ITCZ and MCZ in ITCZ- or MCZ-loaded PLGA MP in all formulations. The drug release percentage from 9.1%-loaded ITCZ-PLGA7505 MP at 24 h was almost 50%, which was higher than that of ITCZ powder. The drug release percentage from MCZ-loaded PLGA7505 MP at 4 h was over 80%, which was higher than that of MCZ powder. This enhancement of release rate is caused by the amorphization of ITCZ or MCZ in the PLGA matrix. MCZ-loaded PLGA7510 MP showed a sustained release profile up to 24 h, suggesting that MCZ exists in an amorphous form in the PLGA matrix;however, the release rate declined owing to the large molecular weight of PLGA. Therefore, the release enhancement of antifungal drugs loaded on PLGA MP could be achieved by their amorphization using a co-grinding method with ball milling.

关键词： Co-Grinding Method Ball Milling Poly (Lactide-co-Glycolide) Itraconazole Miconazole Amorphization

Preparation and Characterization of Orally Fast-Disintegrating Mini-Tablets Containing Diphenhydramine Hydrochloride and Aspartic or Glutamic Acid as an Umami Amino Acid

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Pharmacology & Pharmacy 2021年第12期12卷 283-292页

作者： Kyoko Ohkawa Haruka Nishikawa honami kojima Takayoshi Okuno Rio Uno Miyako Yoshida Takahiro Uchida Faculty of Pharmaceutical Sciences Mukogawa Women’s University Nishinomiya Japan

The aim of this study was to prepare diphenhydramine hydrochloride (DPH)-loaded orally fast-disintegrating mini-tablets (OFDMTs) containing either L-aspartic acid (Asp) or L-glutamic acid (Glu) as bitterness-suppressant, to characterize the prepared tablets and to evaluate their bitterness under conditions mimicking those of the oral cavity. The preparation of five formulation batches of the OFDMTs involved mixing DPH, with or without two different concentrations of Asp or Glu, and a premix containing a disintegrating agent. When all ingredients were well mixed, the mixture was directly compacted to form small (4 mm diameter) DPH-loaded OFDMTs. There were only small differences between the tablets with respect to mass, diameter, width and hardness. The disintegration times of the five formulation batches of DPH-loaded OFDMTs were measured using the OD-mate, a disintegration test apparatus in which conditions resemble those of the oral cavity. The disintegration times were all within 10 s of exposure to a medium representing the inside of the oral cavity. Rapid release profiles were observed for DPH, Asp and Glu in these dissolution tests. The taste sensor outputs of samples taken at different times (5 - 30 s) from the dissolution test solutions of the four DPH-loaded OFDMTs containing Asp or Glu were significantly inhibited compared with those of control DPH-loaded OFDMT. These results suggest that the inclusion of Asp or Glu in DPH-loaded OFDMTs is sufficient to mask bitterness in the oral cavity for the first 30 s after the tablet is placed in the mouth. It is anticipated that swallowing will have taken place within 30 s.

关键词： Orally Fast Disintegrating Mini-Tablets Diphenhydramine Aspartic Acid Glutamic Acid OD-Mate

The Effect of Food Thickeners on the Bitterness and Dissolution of Amlodipine Besilate Loaded Oral Disintegration Tablets: Assessment of Potential Suitability for Patients with Dysphagia

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Pharmacology & Pharmacy 2022年第11期13卷 368-378页

作者： Akiko Odanaga honami kojima Rio Uno Miyako Yoshida Takahiro Uchida Masaaki Habara Hidekazu Ikezaki Faculty of Pharmaceutical Science Mukogawa Women’s University Nishinomiya Hyogo Japan Intelligent Sensor Technology Inc. Atsugi Kanagawa Japan

The purpose of this research was to evaluate the effect of starch- and xanthan gum-based food thickeners on the bitterness and dissolution of amlodipine besilate (AMPB) loaded orally disintegrating tablets (ODT) for potential use with patients with dysphagia. A conventional dissolution test simulating the oral cavity was performed and the taste sensor output of the dissolved sample was evaluated over a 60-seconds period. When four types of AMPB loaded ODTs were tested alone, at 60 seconds, branded product (A) was the least bitter, followed by generic product (B)/generic product (C) which were equal, and finally generic product (D) which was the most bitter. Inhibition of bitterness of AMPB loaded ODTs mixed thickeners, 1.0 (w/v) % xanthan gum-based food thickener solution was significantly strong. The 7.1 (w/v) % and 4.7 (w/v) % starch-based food thickeners solution also effective in bitterness inhibition compared to the 2.4 (w/v) % starch-based food thickener solution. The dissolution test under pH 1.2 in related to 7.1 (w/v) % and 4.7 (w/v) % starch-based thickener contained each of AMPB loaded ODTs were associated with an almost complete amlodipine (AMP) dissolution (almost 90% at 10 minutes), whereas the 1.0, 2.0, 3.0 (w/v) % xanthan gum-based food thickener solution containing AMPB loaded ODTs did not show complete AMP dissolution and there were large variations in the initial dissolution stage. This suggests that a mixture of xanthan gum-based thickener and AMPB loaded ODT poses a risk of reduction of bioavailability. In conclusion, a mixture of 4.7 (w/v) % or 7.1 (w/v) % starch-based thickener with ODTs provides complete release of AMP and superior bitterness inhibition, so is the best choice for administration to patients with dysphagia.

关键词： Orally Disintegrating Tablet Food Thickener Xanthan Gum-Based Food Thickener Starch-Based Food Thickener Taste Sensor Bitterness Amlodipine

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Evaluation of the Palatability of Dry Syrups and the Bitterness Intensities of Dry Syrups Mixed with Various Beverages

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Pharmacology & Pharmacy 2021年第2期12卷 43-54页

作者： Toshio Kurihara honami kojima Miyako Yoshida Mizuho Oshio Rino Kunikata Haruka Nishikawa Takahiro Uchida Faculty of Pharmaceutical Sciences Mukogawa Women’s University Nishinomiya Japan

The purpose of this study was to evaluate the palatability of dry syrups for pediatric use by human gustatory sensation testing and the artificial taste sensor. The bitterness intensities of dry syrups mixed with various beverages were also evaluated using the taste sensor. Twenty dry-syrup formulations of antibacterial and anti-allergic drugs containing bitter active ingredients, frequently used in pediatric medicine in Japan, were selected for testing. The main factors influencing palatability were determined by factor analysis of data from human gustatory sensation testing using the semantic differential method. It was shown that the bitterness intensity of dry syrups in water could be predicted by the artificial taste sensor. The influence of different beverages (orange juice, milk or cocoa) mixed with the dry syrups was evaluated using the artificial taste sensor. Taste and texture were found to be the principal factors influencing the palatability of dry syrups. While the bitterness intensities of some dry syrups were increased by mixing with orange juice, the bitterness intensities of most dry syrups were decreased by mixing with milk or cocoa. This suggests that one or more constituents of milk or cocoa may reduce the bitterness intensities of dry syrups.

关键词： Palatability Semantic Differential Method Dry Syrup Taste Sensor

Inhibitory Effect of 5-Adenylic Acid on Bitter Taste of Antipsychotic Drugs

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Pharmacology & Pharmacy 2022年第10期13卷 429-446页

作者： Jun Kawahara Rio Uno honami kojima Miyako Yoshida Takahiro Uchida Hidekazu Ikezaki Masaaki Habara Faculty of Pharmaceutical Science Mukogawa Women’s University Nishinomiya Hyogo Japan Intelligent Sensor Technology Inc. Atsugi Kanagawa Japan

The purpose of the present study was to examine the effect of adenylic acid (adenosine 5-monophosphate;AMP), a known nutritional enhancer, on inhibiting the bitterness of antipsychotic medicines administered to patients with mental illnesses, including children. First, we chose four antipsychotic medicines, amitriptyline hydrochloride (AMT), chlorpromazine hydrochloride (CPZ), haloperidol (HPD) and risperidone (RIS) and evaluated the inhibition of their bitterness by AMP through taste sensor measurements. AMP showed a significant bitterness inhibition effect on all drugs. Second, MarvinSketch analysis revealed the potential formation of electrostatic interactions between ionic forms (IV) of AMP and ionic (cationic) forms of each drug, which resulted in bitterness suppression. Third, chemical shift perturbations in 1H-NMR studies suggested an interaction between the phosphate group of AMP and amino group of AMT, CPZ, HPD and RIS. Last, conventional elution experiments of up to 1 min simulating oral cavity conditions were performed for 1 whole AMT tablet, half AMT tablet, crushed half AMT tablet, and crushed AMT tablet containing AMP powder/solution (1, 3 mM potency). The taste sensor output values of the crushed AMT tablet containing AMP powder/solution (1, 3 mM potency) were significantly lower than those of the crushed tablet.

关键词： Adenylic Acid Bitterness Antipsychotic Medicine Amitriptyline Chlorpromazine Haloperidol Risperidone Taste Sensor Drug-Drug Interaction

Preparation and Evaluation of Poly-γ-Glutamic Acid Hydrogel Mixtures with Basic Drugs or Acidic Drugs: Effect on Ease of Swallowing and Taste Masking

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Pharmacology & Pharmacy 2019年第10期10卷 427-444页

作者： honami kojima Saeri Ikegami Shiho Nakamura Haruka Nishikawa Tamami Haraguchi Miyako Yoshida Minoru Ozeki Ikuo Kawasaki Takahiro Uchida Faculty of Pharmaceutical Sciences Mukogawa Women’s University Nishinomiya Japan

The purpose of this study was to prepare a poly-γ-glutamic acid hydrogel (PGA gel), to examine its ease of swallowing using texture profile analysis (TPA) and to evaluate its taste-masking effects on basic or acidic drugs using the artificial taste sensor. Using TPA, 0.5% and 1.0% PGA gels, 0.5% and 1.0% agar and 1.0% ι-carrageenan in the absence of drug was examined the hardness, adhesiveness and cohesiveness, ranked according to permission criteria published by the Japanese Consumers Affairs Agency. 0.5% PGA gel and 1.0% agar were classified into grade II. In the taste sensor measurement, the bitterness suppressions by 0.5% PGA gel were larger than that by 1.0% agar in all drugs and the bitterness suppressions of basic drugs in 0.5% PGA gel were more potent than those of acidic drugs in 0.5% PGA gel. 1H-nuclear magnetic resonance spectroscopic analysis was carried out to examine the difference in mechanism of bitterness suppression between basic drugs and acidic drugs mixed with PGA gel. The signals of the proton nearest to the nitrogen atom of basic drugs shifted clearly upfield, suggesting an interaction between the amino group of basic drugs and the carboxyl group of PGA gel. In conclusion, PGA gel is expected to be a useful excipient in formulations contained various drugs, especially basic drugs;it also has advantage for not only increasing ease of swallowing but also masking the bitterness of drugs even though a small amount of a single drug dose might be preferred.

关键词： Poly-γ-Glutamic Acid Hydrogel Bitterness Taste Sensor

Therapeutic strategies for targeting the ovarian tumor stroma

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World Journal of Clinical Cases 2014年第6期2卷 194-200页

作者： Song Yi Ko honami Naora Department of Molecular and Cellular Oncology University of Texas MD Anderson Cancer Center

Epithelial ovarian cancer is the most lethal type of gynecologic malignancy. Sixty percent of women who are diagnosed with ovarian cancer present with advancedstage disease that involves the peritoneal cavity and these patients have a 5-year survival rate of less than 30%. For more than two decades, tumor-debulking surgery followed by platinum-taxane combination chemotherapy has remained the conventional first-line treatment of ovarian cancer. Although the initial response rate is 70%-80%, most patients with advancedstage ovarian cancer eventually relapse and succumb to recurrent chemoresistant disease. A number of molecular aberrations that drive tumor progression have been identified in ovarian cancer cells and intensive efforts have focused on developing therapeutic agents that target these aberrations. However, increasing evidence indicates that reciprocal interactions between tumor cells and various types of stromal cells also play important roles in driving ovarian tumor progression and that these stromal cells represent attractive therapeutic targets. Unlike tumor cells, stromal cells within the tumor microenvironment are in general geneticallystable and are therefore less likely to become resistant to therapy. This concise review discusses the biological significance of the cross-talk between ovarian cancer cells and three major types of stromal cells(endothelial cells, fibroblasts, macrophages) and the development of new-generation therapies that target the ovarian tumor microenvironment.

关键词： Ovarian cancer Tumor stroma Endothelial cells Fibroblasts Macrophages Targeted therapy

Comparative Expression Profiling of Lactogenic Hormone Receptor and It’s Signaling Molecules of Bovine Mammary Glands during lactation

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Open Journal of Animal Sciences 2015年第2期5卷 106-113页

作者： Shinichi Yonekura honami Miyazaki Yukako Tokutake Department of Interdisciplinary Genome Sciences and Cell Metabolism Institute for Biomedical Sciences Interdisciplinary Cluster for Cutting Edge Research (ICCER) Shinshu University Minami-minowa Nagano Japan Graduate School of Agriculture Shinshu University Minami-minowa Nagano Japan Interdisciplinary Graduate School of Science and Technology Shinshu University Minami-minowa Nagano Japan

Milk synthesis is known to be modulated by peptide hormones such as prolactin (PRL), growth hormone (GH), and insulin-like growth factor I (IGF-I). Previous studies suggested that PRL and IGF-I acted directly on mammary epithelial cells and were involved in lactation. Meanwhile, GH is thought to be indirectly involved in lactation by stimulating the secretion of IGF-I. It is controversial as growth hormone receptors (GHR) is expressed in the mammary epithelial cells. In order to clarify whether GH acted directly on mammary gland tissue, we investigated the prolactin receptors (PRLR), IGF-I receptors (IGF-IR), and GHR as well as the gene expression levels of the downstream signaling molecule for each receptor in the mammary gland tissue of Holstein cows during different stages of lactation. The results revealed that the mRNA expressions of PRLR and IGF-IR were highest during early lactation, and the mRNA expression of the GHR was highest during mid-lactation. We also found that the expression profiling of the signal transducer and activator of transcription 5 (STAT5) genes was similar to that of the GHR gene. On the other hand, the expression profiling of the PRLR gene was similar to that of the SHP2 gene. These results suggest that GH acts on the mammary glands directly, milk synthesis and secretion are chiefly stimulated in mid-lactation, and the timing of the action is different for PRL and IGF-I.

关键词： Lactation Growth Hormone Prolactin Signal Transduction Mammary Gland

Temporal Sequence of Sweetness Perception in Fruit-Flavored Tea: A Descriptive Report on the Influence of Sucrose Concentrations on the Sensation

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Food and Nutrition Sciences 2019年第1期10卷 110-117页

作者： Suzuka Akemura Nomo Hasebe Madoka Kasahara honami Sakai Eri Sanada Yozo Miyaoka Department of Health and Nutrition Niigata University of Health and Welfare Niigata Japan

The goals of this study were to examine, using the temporal dominance of sensations (TDS) method, the effects of 1) the sucrose concentration on the temporal sequence of sweetness perception in four fruit-flavored (lemon, peach, strawberry, and vanilla) teas with 0.05, 0.15, and 0.25 M sucrose;and 2) participants’ sex on this temporal sequence. Twenty-four healthy young adults were assigned to female (n = 12) and male (n = 12) groups. Both groups evaluated five sensory attributes in 12 samples (four fruit-flavored teas, each with three sucrose concentrations). As in our preceding study [1], two sensations, sweetness and fruitiness, were dominant after ingesting the 12 teas in both groups, but the temporal sequence of sweetness perception differed between the two groups. On average, the male group reported the first appearance of sweetness earlier in the samples with 0.05 M sucrose compared with the female group, with the samples containing 0.15 and 0.25 M sucrose. The average durations of the sweetness sensation were different between the male and female groups as well as among the sucrose concentrations and the four flavors tested.

关键词： Tea Sweetness Flavor Sucrose Concentration Temporal Dominance of Sensations Sex Differences