M. Pająk, M. Woźniczka, M. Świątek, Bartłomiej Czerwiński, J. Włodarczyk, J. Fichna
The present work describes the complexation properties of two synthetic nucleosides (used as ligands), i.e. β-D-ribofuranoside-4-pyrimidinone (ribo) and β-D-deoxyribofuranoside-4-pyrimidinone (deoxy) with Ag(I) ions in aqueous solution. The stability constants of the studied coordination entities were calculated potentiometrically. The logarithm values of the overall stability constants of the coordination entities were found to be [Ag-deoxy]+ = 3.07, [Ag-(deoxy)2]+ = 6.90, [Ag-ribo]+ = 3.00 and [Ag-(ribo)2]+ = 6.63. Based on the species distribution curves as a function of CL/CM, the percentage of each coordination entity formed in aqueous solution was estimated (12 % [Ag-deoxy]+; 36 % [Ag-(deoxy)2]+; 16 % [Ag-ribo]+; 26 % [Ag-(ribo)2]+). It was found that the ligands form coordination entities with Ag(I) ions with stoichiometric ratios M : L = 1 : 1 and 1 : 2. Such coordination entities may show potential antiviral, antibacterial, and antitumor properties, which warrants further in vitro and in vivo studies. They may also be of great interest for their application in nanobiotechnology.
{"title":"COMPLEX-FORMING PROPERTIES OF SYNTHETIC PYRIMIDINONE NUCLEOSIDES WITH Ag(I) IONS IN AN AQUEOUS SOLUTION","authors":"M. Pająk, M. Woźniczka, M. Świątek, Bartłomiej Czerwiński, J. Włodarczyk, J. Fichna","doi":"10.32383/appdr/162766","DOIUrl":"https://doi.org/10.32383/appdr/162766","url":null,"abstract":"The present work describes the complexation properties of two synthetic nucleosides (used as ligands), i.e. β-D-ribofuranoside-4-pyrimidinone (ribo) and β-D-deoxyribofuranoside-4-pyrimidinone (deoxy) with Ag(I) ions in aqueous solution. The stability constants of the studied coordination entities were calculated potentiometrically. The logarithm values of the overall stability constants of the coordination entities were found to be [Ag-deoxy]+ = 3.07, [Ag-(deoxy)2]+ = 6.90, [Ag-ribo]+ = 3.00 and [Ag-(ribo)2]+ = 6.63. Based on the species distribution curves as a function of CL/CM, the percentage of each coordination entity formed in aqueous solution was estimated (12 % [Ag-deoxy]+; 36 % [Ag-(deoxy)2]+; 16 % [Ag-ribo]+; 26 % [Ag-(ribo)2]+). It was found that the ligands form coordination entities with Ag(I) ions with stoichiometric ratios M : L = 1 : 1 and 1 : 2. Such coordination entities may show potential antiviral, antibacterial, and antitumor properties, which warrants further in vitro and in vivo studies. They may also be of great interest for their application in nanobiotechnology.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45510200","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}
Chirality is a binary yes/no molecular property that nevertheless can be described by a continuous chirality measure function. Chirality measure values can be understood as sensitive descriptors of molecular shape. In this study, we evaluated the role of quantitative chirality (measures) in binding of androgens to their receptor. We demonstrate that a simple Quantitative Structure-Activity Relationship equation correlating the binding affinity with the partial charges of pharmacophoric oxygen atoms is significantly improved upon introducing quantitative chirality descriptors as additional variables. In such models, the charge descriptors account for the strength of the formed hydrogen bonds. However, the picture is completed by the chirality measures that indirectly contain information on the geometries of the hydrogen bond networks and subtle differences in the van der Waals contacts connected with different local or global shapes of the molecules. The model case studied here (11 simple and very similar steroids) proves that both global and local chirality is important in the androgen binding to their receptors.
{"title":"Quantitative chirality in the binding of androgens to their receptor","authors":"Piotr F. J. Lipiński, J. Dobrowolski, A. Baraniak","doi":"10.32383/appdr/161082","DOIUrl":"https://doi.org/10.32383/appdr/161082","url":null,"abstract":"Chirality is a binary yes/no molecular property that nevertheless can be described by a continuous chirality measure function. Chirality measure values can be understood as sensitive descriptors of molecular shape. In this study, we evaluated the role of quantitative chirality (measures) in binding of androgens to their receptor. We demonstrate that a simple Quantitative Structure-Activity Relationship equation correlating the binding affinity with the partial charges of pharmacophoric oxygen atoms is significantly improved upon introducing quantitative chirality descriptors as additional variables. In such models, the charge descriptors account for the strength of the formed hydrogen bonds. However, the picture is completed by the chirality measures that indirectly contain information on the geometries of the hydrogen bond networks and subtle differences in the van der Waals contacts connected with different local or global shapes of the molecules. The model case studied here (11 simple and very similar steroids) proves that both global and local chirality is important in the androgen binding to their receptors.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41529555","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}
T. Pawiński, I. Szlaska, Monika Kukiełka, Kinga Kośnik
This paper describes a simple, rapid and cost-effective HPLC-UV method for the determination of venlafaxine and its active metabolite O-desmethylvenlafaxine in human plasma. Sample preparation is based on a liquid-liquid extraction procedure with a short extraction time. Prazosine hydrochloride was used as the internal standard. The HPLC separation was performed on a Supelcosil LC-CN column, using a mobile phase consisting acetonitrile : 25 mM phosphate buffer at pH 3,5 (15:85 v/v). The calibration curve is linear in the concentrations range of 25-1000 ng/mL, which is suitable for pharmacokinetic studies of venlafaxine hydrochloride following of dosing from 37.5 mg to 375.0 mg per day. The method was fully validated according to the international guidances,
{"title":"Validated HPLC-UV method for determination of venlafaxine and its metabolite - o-desmethylvenlafaxine in human plasma","authors":"T. Pawiński, I. Szlaska, Monika Kukiełka, Kinga Kośnik","doi":"10.32383/appdr/159659","DOIUrl":"https://doi.org/10.32383/appdr/159659","url":null,"abstract":"This paper describes a simple, rapid and cost-effective HPLC-UV method for the determination of venlafaxine and its active metabolite O-desmethylvenlafaxine in human plasma. Sample preparation is based on a liquid-liquid extraction procedure with a short extraction time. Prazosine hydrochloride was used as the internal standard. The HPLC separation was performed on a Supelcosil LC-CN column, using a mobile phase consisting acetonitrile : 25 mM phosphate buffer at pH 3,5 (15:85 v/v). The calibration curve is linear in the concentrations range of 25-1000 ng/mL, which is suitable for pharmacokinetic studies of venlafaxine hydrochloride following of dosing from 37.5 mg to 375.0 mg per day. The method was fully validated according to the international guidances,","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42060284","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}
Małgorzata Belczyk, M. Knapik-Czajka, A. Gawedzka, K. Mikołajczyk, J. Drag
Mitochondrial 2-oxoglutarate dehydrogenase complex (2-OGDH) that consists of multiple copies of 3 catalytic subunits (E1, E2, E3) is a regulatory enzyme of tricarboxylic acid cycle. 2-OGDH together with branched chain α-ketoacid dehydrogenase (BCKDH) and pyruvate dehydrogenase (PDH) belongs to the 2-oxoacid dehydrogenases family. It was shown that in protein-restricted rats simvastatin stimulated liver BCKDH, whereas it exerted no effect on BCKDH in rats fed a standard diet. We hypothesized that combination of simvastatin and low-protein diet could have an impact on renal 2-OGDH. The purpose of the study was to determine the effect of combination of simvastatin and low-protein diet on renal 2-OGDH in rats. Simvastatin (80 mg/kg b.wt/day) or the vehicle (0.3% methylcellulose) were administered orally (for 14 days) to rats fed low-protein (8% protein) or standard (23% protein) diet. 2-OGDH activity, protein levels and mRNA levels for E1 and E2 subunits were determined. In addition, serum creatinine level was measured. Results: The combination of simvastatin and low-protein diet elicited the increase of renal 2-OGDH activity that corresponded to the increase of E1 protein, but not of E1 mRNA level. In contrast, simvastatin treatment did not affect 2-OGDH activity, nor protein and mRNA levels of E1 in rats fed standard diet. Serum creatinine levels were not changed upon simvastatin administration in any group. In conclusion, the results of present study indicate that combination of simvastatin and low-protein diet induces stimulation of renal 2-OGDH complex probably at post-transcriptional level.
{"title":"A combination of simvastatin and low-protein diet increases renal 2-oxoglutarate dehydrogenase activity in rats","authors":"Małgorzata Belczyk, M. Knapik-Czajka, A. Gawedzka, K. Mikołajczyk, J. Drag","doi":"10.32383/appdr/159789","DOIUrl":"https://doi.org/10.32383/appdr/159789","url":null,"abstract":"Mitochondrial 2-oxoglutarate dehydrogenase complex (2-OGDH) that consists of multiple copies of 3 catalytic subunits (E1, E2, E3) is a regulatory enzyme of tricarboxylic acid cycle. 2-OGDH together with branched chain α-ketoacid dehydrogenase (BCKDH) and pyruvate dehydrogenase (PDH) belongs to the 2-oxoacid dehydrogenases family. It was shown that in protein-restricted rats simvastatin stimulated liver BCKDH, whereas it exerted no effect on BCKDH in rats fed a standard diet. We hypothesized that combination of simvastatin and low-protein diet could have an impact on renal 2-OGDH. The purpose of the study was to determine the effect of combination of simvastatin and low-protein diet on renal 2-OGDH in rats. Simvastatin (80 mg/kg b.wt/day) or the vehicle (0.3% methylcellulose) were administered orally (for 14 days) to rats fed low-protein (8% protein) or standard (23% protein) diet. 2-OGDH activity, protein levels and mRNA levels for E1 and E2 subunits were determined. In addition, serum creatinine level was measured. Results: The combination of simvastatin and low-protein diet elicited the increase of renal 2-OGDH activity that corresponded to the increase of E1 protein, but not of E1 mRNA level. In contrast, simvastatin treatment did not affect 2-OGDH activity, nor protein and mRNA levels of E1 in rats fed standard diet. Serum creatinine levels were not changed upon simvastatin administration in any group. In conclusion, the results of present study indicate that combination of simvastatin and low-protein diet induces stimulation of renal 2-OGDH complex probably at post-transcriptional level.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47605321","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}
Flavonoids are secondary plant metabolites that have long been included in the human diet. These natural products are well known for their beneficial effects on health. Thus, in this study, the in vitro inhibitory activity of 28 different flavonoids (1-28) against acetylcholinesterase was evaluated, and the type of inhibition for the most active compound (12) was studied. Acetylcholinesterase (AChE) inhibitors are considered the main class of medication used for the treatment of the primary dementia phase in Alzheimer's disease (AD). Our study used galantamine as a positive control and showed that 7,8-dihydroxyflavone (12) has the highest anti-acetylcholinesterase activity. The inhibitory type of 7,8-dihydroxyflavone, which is non-competitive inhibition, was determined for the first time. Furthermore, the obtained data allowed us to identify the characteristic flavonoid structure that facilitates AChE inhibition: the presence of a hydroxyl group at C7 in the benzo-γ-pyrane ring of the molecule.
{"title":"Acetylcholinesterase inhibitors: structure-activity relationship and kinetic studies on selected flavonoids","authors":"K. Jakimiuk, Diana Nazaruk, M. Tomczyk","doi":"10.32383/appdr/159798","DOIUrl":"https://doi.org/10.32383/appdr/159798","url":null,"abstract":"Flavonoids are secondary plant metabolites that have long been included in the human diet. These natural products are well known for their beneficial effects on health. Thus, in this study, the in vitro inhibitory activity of 28 different flavonoids (1-28) against acetylcholinesterase was evaluated, and the type of inhibition for the most active compound (12) was studied. Acetylcholinesterase (AChE) inhibitors are considered the main class of medication used for the treatment of the primary dementia phase in Alzheimer's disease (AD). Our study used galantamine as a positive control and showed that 7,8-dihydroxyflavone (12) has the highest anti-acetylcholinesterase activity. The inhibitory type of 7,8-dihydroxyflavone, which is non-competitive inhibition, was determined for the first time. Furthermore, the obtained data allowed us to identify the characteristic flavonoid structure that facilitates AChE inhibition: the presence of a hydroxyl group at C7 in the benzo-γ-pyrane ring of the molecule.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42158818","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}
Jakub Strzemieczny, Bogusława Musiał, Agnieszka Pawlaczyk, M. Sznitowska, D. Siluk
With increasing environmental pollution and tendency to smoking, the number of patients suffering from chronic obstructive pulmonary disease is increasing and a demand for generic products for the treatment of chronic obstructive pulmonary disease (COPD) is growing. The long process of generic formulation development can be accelerated by using an inhaler with suitable fluid dynamics features. This paper presents a study of a newly patented single-dose Memmatec Mora® inhaler in two versions: with grid openings 1.0 (A) and 0.5 mm (B), using Seebri Breezhaler® as a reference product. The studies were conducted with inhalation powders containing 44μg glycopyrronium bromide placed in a capsule. The manuscript presents studies during the selection of a generic inhaler within the course of inhalation powder development by a pharmaceutical company. The fluid dynamics features of the inhalers and the dose delivered were determined. The aerodynamic particle size distribution (APSD) and the inhalable dose were tested using a cascade impactor. The delivery dose for the Breezhaler, Mora A and Mora B inhalers for a volumetric flow of 100 L×min-1 was 38.5, 40.5 40.3μg, respectively. Fine particle fraction of the inhalers tested was 22.3, 24.6 25.5μg, respectively. Results of the study indicate that increase of the glycopyrronium bromide inhalation dose can be achieved not only by changes in the manufacturing technology of inhalation powder, hard capsule technology or addition of best quality raw materials, but also by the use of a properly selected inhaler with specific fluid dynamics features.
随着环境污染的加剧和吸烟的趋势，慢性阻塞性肺疾病患者的数量不断增加，对慢性阻塞性肺疾病(COPD)治疗的仿制产品的需求不断增长。通过使用具有适当流体动力学特性的吸入器，可以加快仿制制剂开发的漫长过程。本文介绍了一种新专利的单剂量Memmatec Mora®吸入器的研究，该吸入器有两个版本:栅格开口1.0 (a)和0.5 mm (B)，使用Seebri Breezhaler®作为参考产品。研究人员将含有44μg甘溴铵的吸入粉末放入胶囊中。手稿提出了研究期间的选择一个通用吸入器在吸入粉末开发过程中由制药公司。确定了吸入器的流体动力学特性和所给剂量。采用叶栅冲击器测试了空气动力学粒径分布(APSD)和可吸入剂量。在体积流量为100 L×min-1时，Breezhaler、Mora和Mora B吸入器的给药剂量分别为38.5、40.5、40.3μg。吸入器细颗粒物含量分别为22.3、24.6、25.5μg。研究结果表明，增加甘溴铵吸入剂量不仅可以通过改变吸入粉的制造工艺、硬胶囊技术或添加最优质的原料来实现，还可以通过选择适当的具有特定流体动力学特性的吸入器来实现。
{"title":"Study of glycopyrrolate dry powder behavior in new single dose inhalers under generic product development","authors":"Jakub Strzemieczny, Bogusława Musiał, Agnieszka Pawlaczyk, M. Sznitowska, D. Siluk","doi":"10.32383/appdr/160204","DOIUrl":"https://doi.org/10.32383/appdr/160204","url":null,"abstract":"With increasing environmental pollution and tendency to smoking, the number of patients suffering from chronic obstructive pulmonary disease is increasing and a demand for generic products for the treatment of chronic obstructive pulmonary disease (COPD) is growing. The long process of generic formulation development can be accelerated by using an inhaler with suitable fluid dynamics features. This paper presents a study of a newly patented single-dose Memmatec Mora® inhaler in two versions: with grid openings 1.0 (A) and 0.5 mm (B), using Seebri Breezhaler® as a reference product. The studies were conducted with inhalation powders containing 44μg glycopyrronium bromide placed in a capsule. The manuscript presents studies during the selection of a generic inhaler within the course of inhalation powder development by a pharmaceutical company. The fluid dynamics features of the inhalers and the dose delivered were determined. The aerodynamic particle size distribution (APSD) and the inhalable dose were tested using a cascade impactor. The delivery dose for the Breezhaler, Mora A and Mora B inhalers for a volumetric flow of 100 L×min-1 was 38.5, 40.5 40.3μg, respectively. Fine particle fraction of the inhalers tested was 22.3, 24.6 25.5μg, respectively. Results of the study indicate that increase of the glycopyrronium bromide inhalation dose can be achieved not only by changes in the manufacturing technology of inhalation powder, hard capsule technology or addition of best quality raw materials, but also by the use of a properly selected inhaler with specific fluid dynamics features.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47378679","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}
K. Wróblewski, I. Dybała, A. Petruczynik, M. Szultka-Młyńska, Daria Janiszewska, J. Rog, H. Karakuła-Juchnowicz, D. Juchnowicz, B. Buszewski
Carbamazepine (CBZ) is an anticonvulsant drug, widely used also in various disorders like neuropathic pain, bipolar affective disorder, resistant schizophrenia, and trigeminal neuralgia. Appropriate analytical procedures are necessary to monitor, detect and quantify CBZ in pharmaceutical formulations and biological samples. The search for new methods for drug determination is one of the most important challenges of modern scientific research. It is important to study the chromatographic conditions of CBZ analysis, which is necessary for the further development of efficient drug determination methods. In this work, retention, peak symmetry, and system efficiency of CBZ on Polar RP and Phenyl-Hexyl stationary phases were investigated. Various mobile phases containing methanol (MeOH) and/or acetonitrile (ACN) as organic modifiers, acetate buffer, and the addition of diethylamine (DEA) were applied. Different chromatographic systems were compared to obtain satisfying retention, peak shape, and system efficiency. The most optimal chromatographic system with Polar RP column was applied for the determination of CBZ in pharmaceutical formulations, human serum, and saliva by the high-performance liquid chromatography with diode array detection (HPLC-DAD) method. Solid-phase extraction (SPE) method was applied for sample preparation prior to chromatographic analysis. The proposed method was validated for linearity, selectivity, precision, and accuracy. Confirmation of the presence of CBZ and its main metabolites in biological samples obtained from patients was performed using the ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method.
{"title":"Optimization of chromatographic systems for detection and determination of carbamazepine in pharmaceutical formulations, serum, and saliva by HPLC-DAD","authors":"K. Wróblewski, I. Dybała, A. Petruczynik, M. Szultka-Młyńska, Daria Janiszewska, J. Rog, H. Karakuła-Juchnowicz, D. Juchnowicz, B. Buszewski","doi":"10.32383/appdr/161081","DOIUrl":"https://doi.org/10.32383/appdr/161081","url":null,"abstract":"Carbamazepine (CBZ) is an anticonvulsant drug, widely used also in various disorders like neuropathic pain, bipolar affective disorder, resistant schizophrenia, and trigeminal neuralgia. Appropriate analytical procedures are necessary to monitor, detect and quantify CBZ in pharmaceutical formulations and biological samples. The search for new methods for drug determination is one of the most important challenges of modern scientific research. It is important to study the chromatographic conditions of CBZ analysis, which is necessary for the further development of efficient drug determination methods. In this work, retention, peak symmetry, and system efficiency of CBZ on Polar RP and Phenyl-Hexyl stationary phases were investigated. Various mobile phases containing methanol (MeOH) and/or acetonitrile (ACN) as organic modifiers, acetate buffer, and the addition of diethylamine (DEA) were applied. Different chromatographic systems were compared to obtain satisfying retention, peak shape, and system efficiency. The most optimal chromatographic system with Polar RP column was applied for the determination of CBZ in pharmaceutical formulations, human serum, and saliva by the high-performance liquid chromatography with diode array detection (HPLC-DAD) method. Solid-phase extraction (SPE) method was applied for sample preparation prior to chromatographic analysis. The proposed method was validated for linearity, selectivity, precision, and accuracy. Confirmation of the presence of CBZ and its main metabolites in biological samples obtained from patients was performed using the ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43426622","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}
Ondansetron has been widely applied as an antiemetic drug in the treatment or prevention of nausea and vomiting caused by emetic cancer chemotherapy . Fast-release films have the advantages of rapid drug release and improved patients’compliance, especially for the disabled bedridden, the elderly or pediatric patients.The basic film-forming materials were studied through single factor tests and the crystal inhibitors were optimized using solid dispersion technique. The ratio of drug and polymers were optimized by X-ray diffraction (XRD) and Differential Scanning Calorimetry (DSC) which revealed there was no presence of crystal in the optimized solid dispersion. The final film was white thin films and was smooth in surface without obvious bubbles or cracks. Mean weight of each film was 40~50mg. Mean thichness was 60~70μm. Surface pH was 6.4~6.6. The films could release 85% of drug with 1.5min in 0.1mol/L HCl and within 30min in pH6.8PBS. Pharmacolinetic experiment of Ondansetron Hydrochloric solution, marketed films Zuplenz® and the preparation were carried out in rats. As a result, the films of Ondansetron Hydrochloric containing ondansetron solid dispersion had the advantages of fast drug release, improved patient compliance, higher bioavalibility compared to oral solution and the marketed films.
{"title":"Preparation and characterization of fast-release oral film formulation containing ondansetron hydrochloride solid dispersion","authors":"Ting Wei, Zhongxi Zhao, Ya Zhao","doi":"10.32383/appdr/161039","DOIUrl":"https://doi.org/10.32383/appdr/161039","url":null,"abstract":"Ondansetron has been widely applied as an antiemetic drug in the treatment or prevention of nausea and vomiting caused by emetic cancer chemotherapy . Fast-release films have the advantages of rapid drug release and improved patients’compliance, especially for the disabled bedridden, the elderly or pediatric patients.The basic film-forming materials were studied through single factor tests and the crystal inhibitors were optimized using solid dispersion technique. The ratio of drug and polymers were optimized by X-ray diffraction (XRD) and Differential Scanning Calorimetry (DSC) which revealed there was no presence of crystal in the optimized solid dispersion. The final film was white thin films and was smooth in surface without obvious bubbles or cracks. Mean weight of each film was 40~50mg. Mean thichness was 60~70μm. Surface pH was 6.4~6.6. The films could release 85% of drug with 1.5min in 0.1mol/L HCl and within 30min in pH6.8PBS. Pharmacolinetic experiment of Ondansetron Hydrochloric solution, marketed films Zuplenz® and the preparation were carried out in rats. As a result, the films of Ondansetron Hydrochloric containing ondansetron solid dispersion had the advantages of fast drug release, improved patient compliance, higher bioavalibility compared to oral solution and the marketed films.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46425279","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}
M. Filipovic, D. Pecarski, J. Djordjević, M. Ivanović, V. Ilic, M. Lukić
Aging of the skin is a complex and multifactorial biological process, affected by different intrinsic and extrinsic factors. Exogenous factors affecting the process of skin aging, together with nutrition, are topics which currently draw considerable attention. Although it is difficult to accurately define what presents a healthy diet for maintenance of youthful skin, considering the evident lack of clinical data and studies in humans, there are numerous evidence suggesting that the food we eat affects our skin aging and its’ appearance. Well-documented is a fact that the modern diet is a large source of advanced glycation end products and reactive oxygen species – compounds formed during certain food preparation methods which accumulation is associated with different disease and recently, skin aging as well. This review gives the current state of knowledge related to the role which advanced glycation end products and reactive oxygen species, formed during the certain food preparation methods, have in the mechanisms of the premature/extrinsic skin aging. Additionally, it summarizes available information, in the form of recommendations for both the public and nutritional professionals who have an interest in this field, regarding food preparation methods and practices which prevent formation of aforementioned compounds in food and consequently could reduce the food contribution to premature skin aging.
{"title":"Food preparation methods contribution to skin aging: a systematic review","authors":"M. Filipovic, D. Pecarski, J. Djordjević, M. Ivanović, V. Ilic, M. Lukić","doi":"10.32383/appdr/159417","DOIUrl":"https://doi.org/10.32383/appdr/159417","url":null,"abstract":"Aging of the skin is a complex and multifactorial biological process, affected by different intrinsic and extrinsic factors. Exogenous factors affecting the process of skin aging, together with nutrition, are topics which currently draw considerable attention. Although it is difficult to accurately define what presents a healthy diet for maintenance of youthful skin, considering the evident lack of clinical data and studies in humans, there are numerous evidence suggesting that the food we eat affects our skin aging and its’ appearance. Well-documented is a fact that the modern diet is a large source of advanced glycation end products and reactive oxygen species – compounds formed during certain food preparation methods which accumulation is associated with different disease and recently, skin aging as well. This review gives the current state of knowledge related to the role which advanced glycation end products and reactive oxygen species, formed during the certain food preparation methods, have in the mechanisms of the premature/extrinsic skin aging. Additionally, it summarizes available information, in the form of recommendations for both the public and nutritional professionals who have an interest in this field, regarding food preparation methods and practices which prevent formation of aforementioned compounds in food and consequently could reduce the food contribution to premature skin aging.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42628221","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}
A. Nowicka, E. Szałek, L. Gil, M. Šíma, A. Karbownik
The prognosis for patients with acute myeloid leukaemia (AML) varies depending on genetic factors. The presence of mutations in the fms-like tyrosine kinase 3 (FLT3) gene is found in approximately 30% of AML patients. Midostaurin, a first-generation multi-targeted tyrosine kinase inhibitor, is the first FLT3 inhibitor approved for the treatment of newly diagnosed AML patients with the FLT3 mutation in combination with standard induction and consolidation chemotherapy. However, as numerous clinical trials have shown, the list of indications for this drug is likely to be extended. Midostaurin can be administered orally, which improves the patient’s comfort during treatment. In general, it has a favourable safety profile, but interactions with other drugs, such as strong CYP3A4 inhibitors or inducers, which are often used in the concomitant therapy of AML patients, may lead to changes in midostaurin plasma concentrations. In consequence, such interactions may increase the toxicity of the treatment or reduce its therapeutic effect. The aim of this review is to summarise the current knowledge on midostaurin, i.e. its mechanisms of actions, dosage, adverse effects, mechanisms of resistance and limitations to its use. Due to the growing importance of the management of drug-drug interactions mediated via cytochrome CYP3A4, the main focus of this study is the pharmacokinetics of midostaurin and the variability of its plasma concentrations. The Authors emphasise therapeutic drug monitoring with midostaurin as a potential method of managing AML patients with FLT3 mutation.
{"title":"Midostaurin – the First Targeted Therapy Drug for Patients with Acute Myeloid Leukaemia with FLT3 Mutation","authors":"A. Nowicka, E. Szałek, L. Gil, M. Šíma, A. Karbownik","doi":"10.32383/appdr/159470","DOIUrl":"https://doi.org/10.32383/appdr/159470","url":null,"abstract":"The prognosis for patients with acute myeloid leukaemia (AML) varies depending on genetic factors. The presence of mutations in the fms-like tyrosine kinase 3 (FLT3) gene is found in approximately 30% of AML patients. Midostaurin, a first-generation multi-targeted tyrosine kinase inhibitor, is the first FLT3 inhibitor approved for the treatment of newly diagnosed AML patients with the FLT3 mutation in combination with standard induction and consolidation chemotherapy. However, as numerous clinical trials have shown, the list of indications for this drug is likely to be extended. Midostaurin can be administered orally, which improves the patient’s comfort during treatment. In general, it has a favourable safety profile, but interactions with other drugs, such as strong CYP3A4 inhibitors or inducers, which are often used in the concomitant therapy of AML patients, may lead to changes in midostaurin plasma concentrations. In consequence, such interactions may increase the toxicity of the treatment or reduce its therapeutic effect. The aim of this review is to summarise the current knowledge on midostaurin, i.e. its mechanisms of actions, dosage, adverse effects, mechanisms of resistance and limitations to its use. Due to the growing importance of the management of drug-drug interactions mediated via cytochrome CYP3A4, the main focus of this study is the pharmacokinetics of midostaurin and the variability of its plasma concentrations. The Authors emphasise therapeutic drug monitoring with midostaurin as a potential method of managing AML patients with FLT3 mutation.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41946910","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}
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