ADMET and DMPK最新文献_第8页

Effect of divalent and trivalent metal ions on artificial membrane permeation of fluoroquinolones. 二价和三价金属离子对氟喹诺酮类药物人工膜渗透的影响。

IF 2.5

ADMET and DMPK Pub Date : 2022-01-01 DOI: 10.5599/admet.1427

Nanami Nakatani, Kiyohiko Sugano

{"title":"Effect of divalent and trivalent metal ions on artificial membrane permeation of fluoroquinolones.","authors":"Nanami Nakatani, Kiyohiko Sugano","doi":"10.5599/admet.1427","DOIUrl":"https://doi.org/10.5599/admet.1427","url":null,"abstract":"The purpose of the present study was to evaluate the predictability of PAMPA for the effect of metal ions on the bioavailability of fluoroquinolones (FQ). Eleven FQs and seven metal ions were employed in this study. The PAMPA membrane consisted of a 10 % soybean lecithin (SL) - decane solution. A drug solution in MES buffer with or without a metal ion (added as a chloride salt) was added to the donor compartment. In the absence of metal ions, FQ showed relatively high permeability (> 5 × 10-6 cm/sec) in SL-PAMPA despite their hydrophilic and zwitterionic properties. As the PAMPA permeability ratio with/without metal ions became smaller, the urinary excretion and AUC ratios tended to be smaller, suggesting that SL-PAMPA is a suitable in vitro model to evaluate the potential effect of metal ions on the bioavailability of FQ. However, the reduction in AUC and urinary excretion was overestimated for low solubility metal ion formulations (dried aluminum hydroxide gel and La2(CO3)3・8H2O). In such cases, the dissolution of the metal ion formulations and the permeation of FQs should be simultaneously evaluated.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"10 4","pages":"289-297"},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10800157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Thickness of the aqueous boundary layer in stirred microtitre plate permeability assays (PAMPA and Caco-2), based on the Levich equation. 基于Levich方程的搅拌微滴板渗透性测定(PAMPA和Caco-2)中水边界层厚度

IF 2.5

ADMET and DMPK Pub Date : 2022-01-01 DOI: 10.5599/admet.1568

Alex Avdeef

引用次数: 0

Impact of gastrointestinal differences in veterinary species on the oral drug solubility, in vivo dissolution, and formulation of veterinary therapeutics 兽药物种胃肠道差异对口服药物溶解度、体内溶出度和兽药制剂的影响

IF 2.5

ADMET and DMPK Pub Date : 2022-01-01 DOI: 10.5599/admet.1140

Marilyn N. Martinez, M. Papich, R. Fahmy

{"title":"Impact of gastrointestinal differences in veterinary species on the oral drug solubility, in vivo dissolution, and formulation of veterinary therapeutics","authors":"Marilyn N. Martinez, M. Papich, R. Fahmy","doi":"10.5599/admet.1140","DOIUrl":"https://doi.org/10.5599/admet.1140","url":null,"abstract":"Many gaps exist in our understanding of species differences in gastrointestinal (GI) fluid composition and the associated impact of food intake and dietary composition on in vivo drug solubilization. This information gap can lead to uncertainties with regard to how best to formulate pharmaceuticals for veterinary use or the in vitro test conditions that will be most predictive of species-specific in vivo oral product performance. To address these challenges, this overview explores species-specific factors that can influence oral drug solubility and the formulation approaches that can be employed to overcome solubility-associated bioavailability difficulties. These discussions are framed around some of the basic principles associated with drug solubilization, reported species differences in GI fluid composition, types of oral dosage forms typically given for the various animal species, and the effect of prandial state in dogs and cats. This basic information is integrated into a question-and-answer section that addresses some of the formulation issues that can arise in the development of veterinary medicinals.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"19 1","pages":"1 - 25"},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85821208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Food effect risk assessment in preformulation stage using material sparing μFLUX methodology. 采用省料μFLUX方法评价制剂预配制阶段的食品效应风险。

IF 2.5

ADMET and DMPK Pub Date : 2022-01-01 DOI: 10.5599/admet.1476

Corinne Jankovsky, Oksana Tsinman, Naveen K Thakral

{"title":"Food effect risk assessment in preformulation stage using material sparing μFLUX methodology.","authors":"Corinne Jankovsky, Oksana Tsinman, Naveen K Thakral","doi":"10.5599/admet.1476","DOIUrl":"https://doi.org/10.5599/admet.1476","url":null,"abstract":"The intake of food and meal type can strongly impact the bioavailability of orally administered drugs and can consequently impact drug efficacy and safety. During the early stages of drug development, only a small amount of drug substance is available, and the solubility difference between fasted state simulated intestinal fluid and fed state simulated intestinal fluid may provide an early indication about the probable food effect. But higher drug solubility in fed state simulated intestinal fluid may not always results in an increased oral absorption. In the present research, we demonstrated using 11 model compounds that in addition to the drug dissolution in biorelevant media, the evaluation of the diffusion flux of a drug in solution, across artificial lipid coated membrane, where only the unbound drug crosses the membrane, is a reliable way to predict the food effect. Although, the combination of dissolution and diffusion flux may not reliably predict the food effect in case of drugs undergoing intestinal metabolism or when transporters are involved in the drug absorption, the technique generally provides good information about the food effect at very early stages of drug development that may help in designing a clinical plan by adjusting the drug dose in the fed state.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"10 4","pages":"299-314"},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10800161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Numerical modeling of the dissolution of drug nanocrystals and its application to industrial product development. 药物纳米晶体溶解的数值模拟及其在工业产品开发中的应用。

IF 2.5

ADMET and DMPK Pub Date : 2022-01-01 DOI: 10.5599/admet.1437

Bastian Bonhoeffer, Andreas Kordikowski, Edgar John, Michael Juhnke

{"title":"Numerical modeling of the dissolution of drug nanocrystals and its application to industrial product development.","authors":"Bastian Bonhoeffer, Andreas Kordikowski, Edgar John, Michael Juhnke","doi":"10.5599/admet.1437","DOIUrl":"https://doi.org/10.5599/admet.1437","url":null,"abstract":"The apparent solubility of drug nanocrystals in equilibrium was experimentally determined for a drug-stabilizer system with different particle size distributions. True supersaturation was identified for ultrafine drug nanocrystals with an almost 2-fold increase compared to the thermodynamic solubility of related coarse drug crystals, highlighting their enabling potential to enhance bioavailability. The experimental results were applied to investigate in silico the associated dissolution behavior in a closed system by numerical modeling according to the Ostwald-Freundlich and Noyes-Whitney / Nernst-Brunner equations. Calculated results were found to be in agreement with the experimental results only when the entire particle size distribution of drug nanocrystals was considered. In silico dissolution, studies were conducted to simulate the complex interplay between drug nanocrystals, dissolution conditions and resulting temporal progression during dissolution up to the equilibrium state. Calculations were performed for selected in vivo and in vitro scenarios considering different drug nanocrystal particle size distributions, drug amount, dissolution media and volume. The achieved results demonstrated the importance of ultrafine drug nanocrystals for potential bioavailability improvement and the functional applicability of the modeling approach to investigate their dissolution behavior for configurable formulation variables in product development in terms of in vivo and in vitro relevant conditions.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"10 4","pages":"253-287"},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10800155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ten years for PhysChem Forum-Japan (PCF-J). 物理计划论坛-日本(PCF-J)十年。

IF 2.5

ADMET and DMPK Pub Date : 2022-01-01 DOI: 10.5599/admet.1452

Takashi Mano

引用次数: 0

Development of fiber optic in vitro release testing method for dexamethasone release from the oil solutions. 地塞米松油溶液释放度的光纤体外释放测试方法的建立。

IF 2.5

ADMET and DMPK Pub Date : 2022-01-01 DOI: 10.5599/admet.1465

Filip Kozlina, Ivan Meštrović, Viktor Novak, Nikola Marjanović, Biserka Cetina-Čižmek

{"title":"Development of fiber optic in vitro release testing method for dexamethasone release from the oil solutions.","authors":"Filip Kozlina, Ivan Meštrović, Viktor Novak, Nikola Marjanović, Biserka Cetina-Čižmek","doi":"10.5599/admet.1465","DOIUrl":"https://doi.org/10.5599/admet.1465","url":null,"abstract":"For many parenteral drugs, there is still no standardized method for in vitro release (IVR) testing available. This article presents the development of a new IVR method for oil solutions using a dialysis membrane and USP II apparatus coupled to a fiber optic UV-Vis spectrometer. Experiments were performed using dexamethasone formulations containing castor oil as a solvent with the addition of cosolvents, 20 % (v/v) of isopropanol or Capryol® 90. Based on solubility testing results, castor oil was chosen as the best solvent amongst other vegetable oils, while a significant increase in solubility was obtained by adding either of the two cosolvents. Partitioning experiments were performed to ensure these formulations could achieve prolonged drug release. IVR testing was performed with model formulations and critical test parameters were varied in order to examine the method’s sensitivity. The developed method was sensitive to temperature and stirring rate, while coupling the USP II apparatus with a fiber optic UV-Vis spectrometer enabled complete automation. Moreover, due to the interference of excipients on fiber optic detection of dexamethasone during the release testing, derivative spectroscopy was successfully introduced for the elimination of the interference. The developed IVR method described herein could be useful in preformulation investigations and the early development of novel formulations.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"10 4","pages":"315-329"},"PeriodicalIF":2.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10800158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of silymarin–selenium nanoparticle conjugate and examination of its biological activity in vitro 水飞蓟素-硒纳米颗粒缀合物的合成及其体外生物活性研究

IF 2.5

ADMET and DMPK Pub Date : 2021-11-14 DOI: 10.5599/admet.1023

S. Staroverov, S. Kozlov, A. Fomin, K. Gabalov, Vitaliy Khanadeev, D. Soldatov, I. Domnitsky, L. Dykman, S. Akchurin, O. Guliy

引用次数: 6

Bacteriocin-mediated inhibition of some common pathogens by wild and mutant Lactobacillus species and in vitro amplification of bacteriocin encoding genes 细菌素介导的野生和突变乳杆菌对一些常见病原体的抑制作用及细菌素编码基因的体外扩增

IF 2.5

ADMET and DMPK Pub Date : 2021-11-14 DOI: 10.5599/admet.1053

A. Ahsan, B. Mazhar, Muhammad Kamran Khan, Madiha Mustafa, M. Hammad, N. Ali

{"title":"Bacteriocin-mediated inhibition of some common pathogens by wild and mutant Lactobacillus species and in vitro amplification of bacteriocin encoding genes","authors":"A. Ahsan, B. Mazhar, Muhammad Kamran Khan, Madiha Mustafa, M. Hammad, N. Ali","doi":"10.5599/admet.1053","DOIUrl":"https://doi.org/10.5599/admet.1053","url":null,"abstract":"Lactobacilli are the most common probiotics used in food and other industries because of their capability of producing bacteriocins. Bacteriocins are compounds that are used to kill pathogenic microorganisms. As most bacteria have become resistant to synthetic antibacterial tools, the importance of using probiotics as antibacterial agents has increased. This work was done to check the bacteriocin effect on some common pathogens and the influence of mutation on the bacteriocin activity of Lactobacilli was also investigated. Four strains were isolated, identified from meat and pickles samples via culturing methods, staining, biochemical tests, and ribotyping. Preliminary tests, including Gram staining and catalase test, were done for the confirmation of Lactobacillus species. All strains were gram-positive and catalase-negative. Antibacterial activity was checked against Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus thuringiensis, Escherichia coli, and Salmonella enteritis via agar well diffusion method. The mutations were done using ethidium bromide and the influence of wild and mutants were also checked. Interestingly, mutants developed more virulence than wild ones. It was also observed that they all were sensitive to pepsin. Protein estimation was done via Bradford method. Ribotyping of GCU-W-PS1 revealed 99 % homology with Lactobacillus plantarum and GCU-W-MS1 to Lactobacillus curvatus (99 % homology). Curvacin A, sakacin P, and plantaricin A genes were also amplified using specific primers. Gene sequence showed the presence of curvacin A gene in GCU-W-MS1. It was concluded that lactic acid bacteria could be used as antibacterial tools against common pathogens.","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"49 1","pages":"75 - 87"},"PeriodicalIF":2.5,"publicationDate":"2021-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84920366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Newly discovered Staphylococcus aureus serine hydrolase probe and drug targets 新发现的金黄色葡萄球菌丝氨酸水解酶探针及药物靶点

IF 2.5

ADMET and DMPK Pub Date : 2021-10-28 DOI: 10.5599/admet.1137

M. Fellner

引用次数: 2