Chemical & pharmaceutical bulletin最新文献_第4页

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

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

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

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

Unexpected Surprise in the Reactions of Acetals and Trialkylsilyl Chloride (R₃SiCl): Efficient Deprotection of Aromatic Acyclic Acetals. 缩醛与三烷基硅酰氯（R3SiCl）反应中的意外惊喜：芳香无环缩醛的有效脱保护。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00837

Muthu Karuppasamy, Ishani Uditha Wedage, Mohamed S H Salem, Koji Morimoto, Shinobu Takizawa, Hiromichi Fujioka

引用次数: 0

Efficient Drug Release from Liposomes Introduced Tetrazine Derivatives with Pyrimidine Rings Using Click Chemistry. 利用Click化学方法引入了具有嘧啶环的四嗪衍生物脂质体的高效药物释放。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00591

Mizuho Yamasaki, Masayuki Munekane, Kento Kannaka, Kohei Sano, Toshihide Yamasaki, Takahiro Mukai

{"title":"Efficient Drug Release from Liposomes Introduced Tetrazine Derivatives with Pyrimidine Rings Using Click Chemistry.","authors":"Mizuho Yamasaki, Masayuki Munekane, Kento Kannaka, Kohei Sano, Toshihide Yamasaki, Takahiro Mukai","doi":"10.1248/cpb.c24-00591","DOIUrl":"10.1248/cpb.c24-00591","url":null,"abstract":"We developed a novel drug release method using a bioorthogonal inverse electron demand Diels-Alder reaction on liposomal membranes. Based on reports that replacing pyridine with pyrimidine in tetrazine derivatives improves the reaction rate with strained dienophiles, we investigated if liposomes with tetrazine derivatives containing pyrimidine rings efficiently release drugs via click chemistry. We synthesized and evaluated a tetrazine compound (Tz2) bearing a pyrimidine ring. The reaction rate constant of Tz2 with a norbornene (NB) derivative, 5-norbornenecarboxylic acid (NBCOOH), was higher than that of Tz1 with a pyridine ring. Liposomes containing the synthesized Tz2 (Tz2-liposomes) were prepared, and the reaction between Tz2 and NBCOOH on the liposomal membranes was confirmed using high-resolution mass spectrometry. We encapsulated indium-111-labeled diethylenetriaminepentaacetic acid ([111In]In-DTPA) in liposomes as a model drug. The release of [111In]In-DTPA from Tz2-liposomes was observed after the addition of NBCOOH, with release dependent on NBCOOH concentration. Moreover, release from Tz2-liposomes was significantly higher than that from Tz1-liposomes. These results suggested that tetrazine derivatives with pyrimidine rings efficiently released drugs, likely due to enhanced reaction rates. These findings would advance the development of controlled drug release methods using click chemistry.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 2","pages":"108-111"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490975","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

Effect of Alcohols on the Skin Permeation of Various Drugs. 酒精对各种药物皮肤渗透的影响。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00716

Yuki Ofuchi, Haruna Setoyama, Tsubasa Miyoshi, Kumi Kawano, Yoshiyuki Hattori, Yasuko Obata

{"title":"Effect of Alcohols on the Skin Permeation of Various Drugs.","authors":"Yuki Ofuchi, Haruna Setoyama, Tsubasa Miyoshi, Kumi Kawano, Yoshiyuki Hattori, Yasuko Obata","doi":"10.1248/cpb.c24-00716","DOIUrl":"10.1248/cpb.c24-00716","url":null,"abstract":"In this study we have focused on three types of alcohols: ethanol (EtOH), 2-propanol (IPA), and 1-propanol (NPA), and examined the skin permeability of drugs with different physicochemical properties: ketoprofen (KPF; hydrophobic), cimetidine (CMT; slightly hydrophobic), and caffeine (CF; hydrophilic). The results revealed EtOH particularly enhanced the skin permeation of CF, while IPA enhanced skin permeation regardless of the type of drug. In contrast, NPA significantly increased the skin permeability of KPF and CMT, but had little effect on CF. The differing effects of the alcohols on skin permeation appear to be linked to the physicochemical properties of the drugs. KPF is more hydrophobic than the other drugs, suggesting that it uses the intercellular pathway in the stratum corneum for permeation. CMT has intermediate properties between hydrophilic and hydrophobic, resulting in low skin permeability and ineffective utilization of both the transepidermal and transappendageal pathways. CF mainly utilized the transappendageal pathways for skin permeation because of its smaller molecular weight and more hydrophilic as compared with the other drugs. These results suggest that the effect of different alcohols on enhancing drug skin permeation is not uniform and that the optimal alcohol for enhancing permeability may vary depending on the drug. Therefore, the selection of appropriate additives based on the physicochemical properties of the drug, such as hydrophilicity, hydrophobicity, and molecular weight, is crucial for developing effective transdermal formulation.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 4","pages":"291-297"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771442","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

Evaluation of Time-Dependent Deformation Behavior of Pharmaceutical Excipients in the Tableting Process. 药用赋形剂在片剂过程中随时间变化的变形行为的评价。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00710

Daisuke Mizunaga, Satoru Watano

{"title":"Evaluation of Time-Dependent Deformation Behavior of Pharmaceutical Excipients in the Tableting Process.","authors":"Daisuke Mizunaga, Satoru Watano","doi":"10.1248/cpb.c24-00710","DOIUrl":"https://doi.org/10.1248/cpb.c24-00710","url":null,"abstract":"Tableting is a critical process in the manufacture of pharmaceutical tablets that directly influences product quality. Ensuring consistent quality between the research and development phase and commercial-scale production is essential during scale-up. In this study, we investigated methods for evaluating time-dependent deformation behavior using four excipients that exhibit different compression deformation behaviors. Dicalcium phosphate dihydrate (DCPD) shows no viscoelasticity, whereas lactose monohydrate (LAC), cornstarch (CS), and microcrystalline cellulose (MCC) exhibit viscoelasticity and viscoplasticity, although the degree of viscosity varies between them. In addition to investigating the known strain rate sensitivity (SRS), we performed mechanical energy evaluation based on the area under the force-displacement curve and stress relaxation tests. A trapezoid waveform was applied during the test, with loading punch speeds of 0.5 and 100 mm/s, and a dwell time of 4.5 s. The SRS value for DCPD approached approximately one, indicating no speed dependence, and the SRS increased in the order of LAC < MCC < CS, consistent with previous studies that used a saw-tooth waveform. Among the mechanical energies, the ratio of plastic flow energy to plastic energy, which depends on dwell time, followed a similar trend to SRS for the three materials other than DCPD. We conclude that axial stress relaxation is affected by machine deformation, whereas radial stress relaxation provides insight into the viscous behavior of the material. Under the test conditions, the effects of the punch-displacement profile and compression pressure on the mechanical energy and stress relaxation were more pronounced than those of SRS.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"213-226"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699676","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