Chemical & pharmaceutical bulletin最新文献_第4页

Prediction of Intra-individual Variability in Bioequivalence Studies of 278 Formulations: Comprehensive Analysis Using Physicochemical and Pharmacokinetic Parameters. 278种制剂生物等效性研究的个体差异性预测：使用物理化学和药代动力学参数的综合分析。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00806

Masaki Higashino

{"title":"Prediction of Intra-individual Variability in Bioequivalence Studies of 278 Formulations: Comprehensive Analysis Using Physicochemical and Pharmacokinetic Parameters.","authors":"Masaki Higashino","doi":"10.1248/cpb.c24-00806","DOIUrl":"https://doi.org/10.1248/cpb.c24-00806","url":null,"abstract":"The purpose of the present study was to predict the intra-individual variability (%CVintra) values of Cmax using observed parameters of physicochemical and pharmacokinetic for a variety of formulations. A database was used to summarize the parameters of clinical bioequivalence (BE) studies of oral drugs, including the highest dose tablets, orally disintegrating tablets (ODT), and capsules (278 formulations [238 compounds]). As explanatory variables, %CVintra, inter-individual variability (%CVinter), absolute bioavailability (BA), Tmax, t1/2, dose number (Do), and dissolution rate (D%) were selected. Explanatory variables correlated with %CVintra were identified by multivariate analysis and grouped quantitatively by K-means clustering analysis. The %CVintra predictions compared three models of multiple regression, boosting tree, and neural network. In the neural network, the coefficient of determination (R2) and the root mean square error (RMSE) were the best, with good correlation between the predicted and observed values of the test data (R2 = 0.69). The explanatory variables used in this study are readily available from the literature of reference formulation and in vitro measurement. Therefore, predicting %CVintra for Cmax without conducting pilot studies is useful for clinical planning in the early stages of generic drug development. We believe that we could further contribute to speeding up and reducing the cost of generic drug development.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 4","pages":"349-354"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Two New Halimanes with a γ-Lactone from Croton argyratus. 含γ-内酯的两个新哈利曼类化合物。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00734

Kanami Watanabe, Yohei Saito, Shuichi Fukuyoshi, Katsunori Miyake, David J Newman, Barry R O'Keefe, Kuo-Hsiung Lee, Kyoko Nakagawa-Goto

引用次数: 0

Bioinspired Total Synthesis of Polycyclic Natural Products. 多环天然产物的生物启发全合成。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00843

Hayato Ishikawa

引用次数: 0

Crystalline Phase Transitions of 5'-O-Triethylsilyl-2'-deoxy-5-azacytidine under Varying Temperature and Humidity Conditions and Its Closed Storage Stability. 5'- o -三乙基硅基-2'-脱氧-5-氮杂胞苷在变温变湿条件下的结晶相变及其密闭贮存稳定性

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00676

Masaru Sudo, Makoto Otsuka, Takahiro Matsumoto, Yoshitaka Nakata, Tetsuo Sasaki

{"title":"Crystalline Phase Transitions of 5'-O-Triethylsilyl-2'-deoxy-5-azacytidine under Varying Temperature and Humidity Conditions and Its Closed Storage Stability.","authors":"Masaru Sudo, Makoto Otsuka, Takahiro Matsumoto, Yoshitaka Nakata, Tetsuo Sasaki","doi":"10.1248/cpb.c24-00676","DOIUrl":"https://doi.org/10.1248/cpb.c24-00676","url":null,"abstract":"5'-O-Triethylsilyl-2'-deoxy-5-azacytidine (5'-O-TesDAC) is a prodrug developed to counteract deamination by cytidine deaminase and spontaneous hydrolytic cleavage of the triazine ring. In this study, we have evaluated the physical properties of the crystal forms to determine the optimal crystal form for solid pharmaceutical development. Therefore, the crystalline morphology of 5'-O-TesDAC was assessed using terahertz spectroscopy, in addition to conventional methods (thermal analysis, powder X-ray diffraction, IR absorption spectroscopy and dynamic vapor sorption). Terahertz spectroscopy has the feature of being able to sensitively capture structural changes between lattices and molecules because the absorptions of the terahertz region correspond to those of skeletal vibrations, intermolecular vibrations, and/or lattice vibrations. For this reason, in the evaluation of crystal polymorphism, terahertz spectroscopy was considered to complement methods that have conventionally been used. Furthermore, the metastable state evaluated in this study rapidly transitions to hemihydrate at relative humidity (RH) above 10%, so it could not be measured using attenuated total reflectance-Fourier transform IR (ATR-FTIR), which is performed under atmosphere, whereas terahertz spectroscopy allowed measurements with the sample chamber exposed to dry air easily. The chemical stability was evaluated through a stability test that measured the amount of the main degradation product of each crystalline form using HPLC. As a result, four crystalline forms of 5'-O-TesDAC were identified. The characterization of 5'-O-TesDAC in this study provides valuable information for optimizing the manufacturing parameters of the formulation and selecting appropriate packaging materials for pharmaceutical development.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 4","pages":"374-381"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigation of the Relationship between the Chemical Stability of Itraconazole Adsorbed on Silica during Humidification and NMR Relaxation Using Time-Domain NMR. 用时域核磁共振研究伊曲康唑在二氧化硅上吸附湿化过程中的化学稳定性与核磁共振弛豫的关系。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00056

Kotaro Okada, Myu Hirota, Shungo Kumada, Yoshirnori Onuki

{"title":"Investigation of the Relationship between the Chemical Stability of Itraconazole Adsorbed on Silica during Humidification and NMR Relaxation Using Time-Domain NMR.","authors":"Kotaro Okada, Myu Hirota, Shungo Kumada, Yoshirnori Onuki","doi":"10.1248/cpb.c25-00056","DOIUrl":"https://doi.org/10.1248/cpb.c25-00056","url":null,"abstract":"Silica powder is an essential pharmaceutical ingredient, which in some combinations with drugs, causes chemical instability of the drug adsorbed on it. NMR measurements have been used to determine the drug adsorption state; however, the relationship between drug chemical stability and NMR relaxation, one of the NMR processes, is yet to be thoroughly studied. This work investigated the relationship between the chemical stability of itraconazole (ITZ)-adsorbed silica and its NMR relaxation. NMR can specifically observe 1H nuclei, and this feature was exploited to study only the T1 relaxation of these nuclei in the drug, excluding the silica signal composed of Si and O. ITZ, a poorly water-soluble model drug, was physically adsorbed on nonporous silica (Aerosil 200, AER), and mesoporous silica (Sylysia 320), and the 1H T1 relaxation was measured before storage using the time domain (TD)-NMR technique. The amount of ITZ degradant adsorbed in the silicas was also measured after storage at humidified conditions. Then, the relationship between the degradant amount of ITZ-adsorbed silica after storage and the T1 relaxation rate (1/T1) before storage was investigated. The ITZ-adsorbed silicas showed a positive correlation between the degradant amount and the 1/T1 value. ITZ-adsorbed AER showed a strong positive correlation (R2 = 0.751). Thus, the 1/T1 value may be an efficient parameter to determine the chemical stability of ITZ adsorbed on nonporous silica. The 1/T1 value measurement by TD-NMR could provide new insight for evaluating the chemical stability of solid dosage forms containing silica.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 5","pages":"419-426"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of Glycosylated 3-(3-Amino-3-carboxypropyl)uridine: A Minimum Unit of GlycoRNA. 糖基化3-（3-氨基-3-羧基丙基）尿苷的合成：GlycoRNA的最小单位。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00091

Kazuyuki Ishii, Hikaru Yarita, Shino Manabe

引用次数: 0

Synthesis of the Tricyclic ABC-Ring System of Veratridine. 缬曲啶三环abc环体系的合成。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00156

Keita Shiono, Keisuke Fukaya, Ayami Amano, Daisuke Urabe

引用次数: 0

Total Synthesis and Antibacterial Activity of 5-Geranyloxy-7-hydroxycoumarin and Murrayacoumarin A. 5-香叶氧基-7-羟基香豆素和木耳香豆素A的合成及抗菌活性研究

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00127

Takahito Kuribara, Honoka Yuba, Hina Saito, Akiko Takaya, Masami Ishibashi, Tetsuhiro Nemoto

引用次数: 0

Photo-Enhanced Aqueous Solubilization of Azobenzene-Incorporated Lipids. 偶氮苯脂类的光增强水溶液增溶作用。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00252

Shusuke Tomoshige, Yushi Kawasaki, Junki Morimoto, Naohiro Sato, Yuichi Hashimoto, Minoru Ishikawa

{"title":"Photo-Enhanced Aqueous Solubilization of Azobenzene-Incorporated Lipids.","authors":"Shusuke Tomoshige, Yushi Kawasaki, Junki Morimoto, Naohiro Sato, Yuichi Hashimoto, Minoru Ishikawa","doi":"10.1248/cpb.c25-00252","DOIUrl":"https://doi.org/10.1248/cpb.c25-00252","url":null,"abstract":"Lipids, including fatty acids and phospholipids, play crucial roles in biological systems and are widely utilized in pharmaceutical and biomedical applications. However, their inherent hydrophobicity poses significant challenges for formulation and administration. In this study, we aimed to enhance the aqueous solubility of lipidic compounds by leveraging light-responsive molecular design. We synthesized azo-lipids by incorporating azobenzene units into a fatty acid and phosphatidylcholine, hypothesizing that light-induced trans-cis isomerization would improve solubility. The synthesized compounds exhibited reversible photoisomerization upon alternating UV (365 nm) and visible light irradiation, as confirmed by UV-vis spectroscopy and reverse-phase HPLC. The solubilization of these azo-lipids was quantified under UV-unirradiated and irradiated conditions. Azobenzene-incorporated phosphatidylcholine 2 exhibited a drastic increase in solubilization from 2.030 to 1008 µM (496-fold) after UV irradiation. This significant improvement was attributed to efficient photoisomerization and molecular bending in the cis, cis conformation, reducing intermolecular interactions. Our findings suggest that this on-demand aqueous solubilization strategy offers a novel approach for improving the handling, storage, and potential therapeutic administration of lipid-based compounds.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 6","pages":"568-573"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Highly Precise Anomaly Detection Using Multivariate Statistical Process Control with Appropriate Scaling of Input Variables in Pharmaceutical Continuous Manufacturing. 医药连续生产中输入变量适当缩放的多元统计过程控制高精度异常检测。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00652

Takuya Oishi, Takuya Nagato, Chikara Tsujikawa, Takuya Minamiguchi, Sanghong Kim

{"title":"Highly Precise Anomaly Detection Using Multivariate Statistical Process Control with Appropriate Scaling of Input Variables in Pharmaceutical Continuous Manufacturing.","authors":"Takuya Oishi, Takuya Nagato, Chikara Tsujikawa, Takuya Minamiguchi, Sanghong Kim","doi":"10.1248/cpb.c24-00652","DOIUrl":"https://doi.org/10.1248/cpb.c24-00652","url":null,"abstract":"Multivariate statistical process control (MSPC) has attracted considerable attention as a monitoring method for pharmaceutical continuous manufacturing. However, there are few examples of its application in pharmaceutical manufacturing, and previous studies have shown high false-positive rates. One of the reasons is the use of inappropriate scaling factors. In pharmaceutical processes, the number of experiments for MSPC modeling tends to be small because the active pharmaceutical ingredients are expensive. Subsequently, the standard deviation, a common scaling factor for some variables, becomes too small, and the model may become sensitive to small variations. In this study, we have proposed methods for determining the appropriate scaling factors. These methods were applied to granulation and drying processes in pharmaceutical continuous manufacturing. The MSPC model can detect changes in the process parameters and raw materials used during continuous wet granulation and fluidized bed drying using the proposed scaling method.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"234-245"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0