Pub Date : 2024-05-07DOI: 10.22159/ijap.2024v16i3.50111
V. Maslarska
Objective: A potentiometric titration method was applied to determine non-steroidal anti-inflammatory drugs. The quantitative analysis and the treatment of the primary data are based on a nonlinear regression procedure using commercial software. A general formula valid for every type of acid-base titration, derived before is used as a direct input. Methods: Potentiometric titration of ibuprofen, flurbiprofen, and ketoprofen with sodium hydroxide solution (0.1 mol/l). The solutions of ibuprofen, flurbiprofen, and ketoprofen were prepared in solvent CH3OH: H2O (40:60%). The determination was carried out using a 713 Metrohm pH meter, equipped with Metrohm combined electrode ref. 6.0228.000 Pt1000 with temperature sensor and auto burette. The analysis was performed at ionic strength (I=0.2 mol/l KCl) and t = 25±0.2 °C. Results: The discussed substances were analyzed using potentiometric titration with a standard sodium hydroxide solution (0.1 mol/l). The experimental data V, ml/E, mV and the conditions of these titrations were used as input in the Data Fit program fixing the following parameters Vo =100.0 ml; Ct (NaOH) = 0.1000 mol/l; S = 59.16 mV (corresponding to 25 °C theoretical value) and Kw = 1.2 10-14 (ionic strength 0.2 mol/l). The analytical results for ibuprofen, flurbiprofen and ketoprofen were determined with good accuracy (error+0.4 % foribuprofen+0.2 % for flurbiprofen and+0.2 % for ketoprofen) and precision (1 % for the three). The quantity and acid-base constants of ibuprofen, flurbiprofen, and ketoprofen were determined alone and in tablets. The validation of the method showed very good accuracy and precision. Conclusion: The present approach can be successfully used in routine analysis of the study drugs in quality control laboratories.
{"title":"QUANTITATIVE DETERMINATION OF SOME NON-STEROIDAL ANTI-INFLAMMATORY DRUGSAND THEIR ACID DISSOCIATION CONSTANTS BY DIRECT POTENTIOMETRY","authors":"V. Maslarska","doi":"10.22159/ijap.2024v16i3.50111","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.50111","url":null,"abstract":"Objective: A potentiometric titration method was applied to determine non-steroidal anti-inflammatory drugs. The quantitative analysis and the treatment of the primary data are based on a nonlinear regression procedure using commercial software. A general formula valid for every type of acid-base titration, derived before is used as a direct input.\u0000Methods: Potentiometric titration of ibuprofen, flurbiprofen, and ketoprofen with sodium hydroxide solution (0.1 mol/l). The solutions of ibuprofen, flurbiprofen, and ketoprofen were prepared in solvent CH3OH: H2O (40:60%). The determination was carried out using a 713 Metrohm pH meter, equipped with Metrohm combined electrode ref. 6.0228.000 Pt1000 with temperature sensor and auto burette. The analysis was performed at ionic strength (I=0.2 mol/l KCl) and t = 25±0.2 °C.\u0000Results: The discussed substances were analyzed using potentiometric titration with a standard sodium hydroxide solution (0.1 mol/l). The experimental data V, ml/E, mV and the conditions of these titrations were used as input in the Data Fit program fixing the following parameters Vo =100.0 ml; Ct (NaOH) = 0.1000 mol/l; S = 59.16 mV (corresponding to 25 °C theoretical value) and Kw = 1.2 10-14 (ionic strength 0.2 mol/l). The analytical results for ibuprofen, flurbiprofen and ketoprofen were determined with good accuracy (error+0.4 % foribuprofen+0.2 % for flurbiprofen and+0.2 % for ketoprofen) and precision (1 % for the three). The quantity and acid-base constants of ibuprofen, flurbiprofen, and ketoprofen were determined alone and in tablets. The validation of the method showed very good accuracy and precision.\u0000Conclusion: The present approach can be successfully used in routine analysis of the study drugs in quality control laboratories.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"11 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141004509","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}
Pub Date : 2024-05-07DOI: 10.22159/ijap.2024v16i3.49980
D. Wijaya, Raden Ayu Aulya Herlina, Azizan Haq
Objective: This study aimed to formulate the ethanol extract of kenikir leaf into nanoparticles. The ethanol extract of kenikir leaves loading into nanoparticles can enhanced the stability and effectiveness of antidiabetic activity. Methods: The nanoparticles were prepared using the ionic gelation method with chitosan and variation in sodium tripolyphosphate. The nanoparticle formula was characterized by efficiency encapsulation using spectrophotometry methods and particle size, zeta potential, and polydispersity index using dynamic light scattering (DLS). An antidiabetic activity test was initiated by inducing a high-fat and fructose diet. The parameters tested were decreasing blood glucose levels in rats. Results: The result of the characterization of the nanoparticle was the percent of efficiency encapsulation, particle size, PDI, zeta potential, and pH were carried out to get the best formula. The best formula obtained was the percent of efficiency encapsulation of 96.20±0.0278%, the particle size of 144.6±7.800 nm, zeta potential of+15.32±0.9550 mEv, PDI of 0.48±0.070, and pH of 4.255±0.0035. The decrease in blood glucose levels in the nanoparticles of kenikir leaves extract was not significantly (p>0.05) different from the positive group (metformin) compared to the kenikir leaves extract, which decreased not really significantly. Conclusion: Nanoparticle containing kenikir leaf ethanol extract successfully prepared into nanoparticles and the potential to increase antidiabetic activity.
{"title":"FORMULATION OF NANOPARTICLE CONTAINING KENIKIR LEAF ETHANOL EXTRACTS (COSMOS CAUDATUS KUNTH.) AND ANTIDIABETIC ACTIVITY IN RATS","authors":"D. Wijaya, Raden Ayu Aulya Herlina, Azizan Haq","doi":"10.22159/ijap.2024v16i3.49980","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.49980","url":null,"abstract":"Objective: This study aimed to formulate the ethanol extract of kenikir leaf into nanoparticles. The ethanol extract of kenikir leaves loading into nanoparticles can enhanced the stability and effectiveness of antidiabetic activity.\u0000Methods: The nanoparticles were prepared using the ionic gelation method with chitosan and variation in sodium tripolyphosphate. The nanoparticle formula was characterized by efficiency encapsulation using spectrophotometry methods and particle size, zeta potential, and polydispersity index using dynamic light scattering (DLS). An antidiabetic activity test was initiated by inducing a high-fat and fructose diet. The parameters tested were decreasing blood glucose levels in rats.\u0000Results: The result of the characterization of the nanoparticle was the percent of efficiency encapsulation, particle size, PDI, zeta potential, and pH were carried out to get the best formula. The best formula obtained was the percent of efficiency encapsulation of 96.20±0.0278%, the particle size of 144.6±7.800 nm, zeta potential of+15.32±0.9550 mEv, PDI of 0.48±0.070, and pH of 4.255±0.0035. The decrease in blood glucose levels in the nanoparticles of kenikir leaves extract was not significantly (p>0.05) different from the positive group (metformin) compared to the kenikir leaves extract, which decreased not really significantly.\u0000Conclusion: Nanoparticle containing kenikir leaf ethanol extract successfully prepared into nanoparticles and the potential to increase antidiabetic activity.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"68 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141003382","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}
Pub Date : 2024-05-07DOI: 10.22159/ijap.2024v16i3.50189
Phaneendra Kurapati, Santhivardhan Chinni
Objective: Development and optimization of chrono-modulated pulsatile drug delivery systems (CPDDS) loaded with Rabeprazole for treating nocturnal acid breakthrough in ulcer patients was set as the major objective of this work. Methods: CPDDS were developed to provide drug release as two pulses with predetermined gap. Separate microparticles for delayed instant release (DIR) and delayed extended-release (DER) were formulated. Through the optimization of several formulation and process parameters, ER microparticles were created as matrix microspheres. Central composite design was used to understand how the factors affected the responses. The optimized ER microspheres and plain drug were separately subjected to enteric coating to obtain DER and DIR portion microparticles, respectively. Results: With the exception of stirring speed's impact on drug release, every other factor was found to have a significant influence (p<0.05) on every response. The mechanism underlying the Rabeprazole's delayed prolonged release was explained by the SEM images. The microspheres made with Eudragit RSPO at 0.72 g and polyethylene oxide at 0.5 g for 1 g of Rabeprazole at 400 rpm were shown to be the optimal formulation based on the graphical optimization results. After being coated with a terminal enteric coating, this formulation showed delayed release for a duration of 6 h. Conclusion: After oral administration of equal doses of DIR microcapsules along with the optimized DER microspheres could release Rabeprazole effectively as two different pulses at the desired time intervals.
目标：本研究的主要目标是开发和优化装有雷贝拉唑的慢性调制脉冲给药系统（CPDDS），用于治疗溃疡病人夜间胃酸过多：开发的 CPDDS 以预先确定间隙的两种脉冲形式释放药物。分别配制了缓释速释（DIR）和缓释缓释（DER）微颗粒。通过优化多个配方和工艺参数，ER 微颗粒被制成基质微球。采用中心复合设计来了解各因素对反应的影响。优化后的ER微球和原药分别进行肠溶包衣，得到DER和DIR部分微球：结果：除了搅拌速度对药物释放的影响外，其他因素对每个反应都有显著影响（p<0.05）。扫描电镜图像解释了雷贝拉唑延迟延长释放的机制。根据图形优化结果，1 克雷贝拉唑在 400 转/分的条件下，用 0.72 克 Eudragit RSPO 和 0.5 克聚乙烯氧化物制成的微球是最佳配方。经过肠道末端包衣后，该制剂的延迟释放时间为 6 小时：结论：口服等剂量的 DIR 微胶囊和优化的 DER 微球后，可在所需的时间间隔内以两种不同的脉冲形式有效释放雷贝拉唑。
{"title":"DEVELOPMENT AND OPTIMIZATION OF RABEPRAZOLE CHRONO-MODULATED DRUG DELIVERY SYSTEMS","authors":"Phaneendra Kurapati, Santhivardhan Chinni","doi":"10.22159/ijap.2024v16i3.50189","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.50189","url":null,"abstract":"Objective: Development and optimization of chrono-modulated pulsatile drug delivery systems (CPDDS) loaded with Rabeprazole for treating nocturnal acid breakthrough in ulcer patients was set as the major objective of this work.\u0000Methods: CPDDS were developed to provide drug release as two pulses with predetermined gap. Separate microparticles for delayed instant release (DIR) and delayed extended-release (DER) were formulated. Through the optimization of several formulation and process parameters, ER microparticles were created as matrix microspheres. Central composite design was used to understand how the factors affected the responses. The optimized ER microspheres and plain drug were separately subjected to enteric coating to obtain DER and DIR portion microparticles, respectively.\u0000Results: With the exception of stirring speed's impact on drug release, every other factor was found to have a significant influence (p<0.05) on every response. The mechanism underlying the Rabeprazole's delayed prolonged release was explained by the SEM images. The microspheres made with Eudragit RSPO at 0.72 g and polyethylene oxide at 0.5 g for 1 g of Rabeprazole at 400 rpm were shown to be the optimal formulation based on the graphical optimization results. After being coated with a terminal enteric coating, this formulation showed delayed release for a duration of 6 h.\u0000Conclusion: After oral administration of equal doses of DIR microcapsules along with the optimized DER microspheres could release Rabeprazole effectively as two different pulses at the desired time intervals.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141004886","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}
Pub Date : 2024-05-07DOI: 10.22159/ijap.2024v16i3.50409
Jose Manuel RIOS-RODRIGUEZ, Felipe Dino REYES-RAMIREZ, J. C. RUIZ-SEGURA, J. R. MEDINA-LÓPEZ
Objective: To estimate plasma concentrations-time profiles of Sulfamethoxazole (SMZ) and Trimethoprim (TMP) from fixed-dose combination formulations through in vitro data of dissolution media of physiological relevance and a convolution model. Methods: Dissolution profiles of SMZ/TMP tablets (400/80 mg) were obtained with USP paddle apparatus at 100 rpm and 900 ml of 0.1 N HCl, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer. The reference drug product and two generic formulations were tested. Drugs were quantified by a derivative method. Dissolution profiles were compared with model-dependent and independent methods. SMZ/TMP plasma levels were simulated with dissolution data and published in vivo information. Percent of prediction error (PE) for peak plasma concentration (Cmax) and area under the curve from zero time to infinity (AUC0-inf) at each condition were calculated. Results: In all used conditions, similar dissolution profiles were found excepting for TMP at pH 1.2 (f2<50). The in vitro release performance for reference and generic formulations was explained by the Weibull function only for SMZ at pH 6.8 and TMP at pH 4.5. Values of PE>19% for both generic formulations were found with TMP at pH 1.2. Conclusion: Significant differences in TMP dissolution profiles of generic formulations at pH 1.2 reflect the subsequent differences found in predicted Cmax and AUC0-inf.
{"title":"PREDICTION OF SULFAMETHOXAZOLE AND TRIMETHOPRIM PLASMA LEVELS FROM TABLETS AND DISSOLUTION MEDIA OF PHYSIOLOGICAL RELEVANCE","authors":"Jose Manuel RIOS-RODRIGUEZ, Felipe Dino REYES-RAMIREZ, J. C. RUIZ-SEGURA, J. R. MEDINA-LÓPEZ","doi":"10.22159/ijap.2024v16i3.50409","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.50409","url":null,"abstract":"Objective: To estimate plasma concentrations-time profiles of Sulfamethoxazole (SMZ) and Trimethoprim (TMP) from fixed-dose combination formulations through in vitro data of dissolution media of physiological relevance and a convolution model.\u0000Methods: Dissolution profiles of SMZ/TMP tablets (400/80 mg) were obtained with USP paddle apparatus at 100 rpm and 900 ml of 0.1 N HCl, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer. The reference drug product and two generic formulations were tested. Drugs were quantified by a derivative method. Dissolution profiles were compared with model-dependent and independent methods. SMZ/TMP plasma levels were simulated with dissolution data and published in vivo information. Percent of prediction error (PE) for peak plasma concentration (Cmax) and area under the curve from zero time to infinity (AUC0-inf) at each condition were calculated.\u0000Results: In all used conditions, similar dissolution profiles were found excepting for TMP at pH 1.2 (f2<50). The in vitro release performance for reference and generic formulations was explained by the Weibull function only for SMZ at pH 6.8 and TMP at pH 4.5. Values of PE>19% for both generic formulations were found with TMP at pH 1.2.\u0000Conclusion: Significant differences in TMP dissolution profiles of generic formulations at pH 1.2 reflect the subsequent differences found in predicted Cmax and AUC0-inf.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"62 s286","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141003226","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}
Pub Date : 2024-05-07DOI: 10.22159/ijap.2024v16i3.50705
Doaa Salah ELDIN ABDELFATTAH, Mervat A Fouad, Aliaa N Elmeshad, M. EL-NABARAWI, S. F. Elhabal
Objective: This study aimed to formulate and evaluate the stability profile of an anti-obesity nutraceutical combination in different dosage forms. Methods: Active and inactive ingredients were formulated into pharmaceutical dosage forms. The quality parameters of the dosage forms were determined, followed by accelerated stability testing (40±2 °C and 75±5% Relative Humidity (RH)) for 180 d was completed to evaluate their physical, chemical and microbiological attributes throughout the storage period. Results: Pre-formulation parameters of the powder blend of active and inactive ingredients for each dosage form showed a satisfactory flowability with Hausner's ratio falling between 1.16 and 1.18, average angle of repose between 22.29° and 22.90° and acceptable compressibility with Carr’s index below 25%. Tablets assessments were acceptable with a mean friability value of 0.21±0.03%, hardness of 4.12±0.09 kg/cm2. The average disintegration time of 5 min 10 sec for tablets and 4 min and 30 sec for capsules. The accelerated stability study revealed that tablet dosage forms are stable for longer period that can reach up to 180 d (24 mo real-time), while sachets and capsules are stable for a period of 135 d (18 mo real-time). Conclusion: The anti-obesity blend of White Kidney Bean Extract (WKBE), Propolis Ethanolic Extract (PEE) and CrPic3 can be successfully formulated in acceptable and convenient dosage forms that can be stable for 18-24 mo.
{"title":"FORMULATION AND STABILITY EVALUATION OF ANTI-OBESITY NUTRACEUITCAL BLEND OF WHITE KIDNEY BEAN EXTRACT (PHASEOLUS VULGARIS L.), PROPOLIS ETHANOLIC EXTRACT AND CRPIC3","authors":"Doaa Salah ELDIN ABDELFATTAH, Mervat A Fouad, Aliaa N Elmeshad, M. EL-NABARAWI, S. F. Elhabal","doi":"10.22159/ijap.2024v16i3.50705","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.50705","url":null,"abstract":"Objective: This study aimed to formulate and evaluate the stability profile of an anti-obesity nutraceutical combination in different dosage forms.\u0000Methods: Active and inactive ingredients were formulated into pharmaceutical dosage forms. The quality parameters of the dosage forms were determined, followed by accelerated stability testing (40±2 °C and 75±5% Relative Humidity (RH)) for 180 d was completed to evaluate their physical, chemical and microbiological attributes throughout the storage period.\u0000Results: Pre-formulation parameters of the powder blend of active and inactive ingredients for each dosage form showed a satisfactory flowability with Hausner's ratio falling between 1.16 and 1.18, average angle of repose between 22.29° and 22.90° and acceptable compressibility with Carr’s index below 25%. Tablets assessments were acceptable with a mean friability value of 0.21±0.03%, hardness of 4.12±0.09 kg/cm2. The average disintegration time of 5 min 10 sec for tablets and 4 min and 30 sec for capsules. The accelerated stability study revealed that tablet dosage forms are stable for longer period that can reach up to 180 d (24 mo real-time), while sachets and capsules are stable for a period of 135 d (18 mo real-time).\u0000Conclusion: The anti-obesity blend of White Kidney Bean Extract (WKBE), Propolis Ethanolic Extract (PEE) and CrPic3 can be successfully formulated in acceptable and convenient dosage forms that can be stable for 18-24 mo.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"87 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141003333","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}
Pub Date : 2024-05-07DOI: 10.22159/ijap.2024v16i3.50040
Irma Ratna Kartika, Teni Ernawati, S. A. Jusman, M. Sadikin
Objective: The goal of this study was to create vitamin E derivatives and explore their potential anticancer properties using a computational approach. Methods: The Steglich method was used for the synthesis of the vitamin E-fatty acid (pentanoic acid, heptanoic acid, and octanoic acid) derivatives, with N,N'-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) as the catalysts. The structure of the synthesized products was determined by ultraviolet-visible (UV-Vis) spectroscopy, fourier transform infrared (FTIR) spectroscopy, and liquid chromatography-mass spectrometry (LC-MS). Molecular docking was carried out on the succinate dehydrogenase (SDH) enzyme using AutoDockTools. Results: α–Tocopherol pentanoate (α–TP), α–tocopherol heptanoate (α–TH), and α–tocopherol octanoate (α–TO) were the three vitamin E derivatives synthesized in this study. Based on the results of molecular docking, the novel compounds (α–TP, α–TH, and α–TO) generated bond energies of-10.57,-9.61, and-9.20 kcal/mol, respectively. Conclusion: All newly synthesized compounds exhibited lower binding affinity values than α–tocopherol (α–T). This confirms that these compounds might not provide greater advantages than α-tocopherol in terms of inhibitory effects on mitochondrial complex II (CII).
目的：本研究的目的是利用计算方法创建维生素 E 衍生物并探索其潜在的抗癌特性：本研究的目的是利用计算方法创建维生素 E 衍生物并探索其潜在的抗癌特性：以N,N'-二环己基碳二亚胺（DCC）和4-二甲氨基吡啶（DMAP）为催化剂，采用Steglich法合成维生素E-脂肪酸（戊酸、庚酸和辛酸）衍生物。合成产物的结构通过紫外-可见（UV-Vis）光谱、傅立叶变换红外（FTIR）光谱和液相色谱-质谱（LC-MS）测定。结果：α-生育酚戊酸酯（α-TP）、α-生育酚庚酸酯（α-TH）和α-生育酚辛酸酯（α-TO）是本研究合成的三种维生素 E 衍生物。根据分子对接的结果，新型化合物（α-TP、α-TH 和 α-TO）产生的键能分别为-10.57、-9.61 和-9.20 kcal/mol：结论：所有新合成的化合物的结合亲和值都低于α-生育酚（α-T）。这证明这些化合物对线粒体复合体 II（CII）的抑制作用可能并不比α-生育酚更强。
{"title":"STUDY OF THE INHIBITORY EFFECTS OF VITAMIN E DERIVATIVES ON MITOCHONDRIAL COMPLEX II SUBUNIT USING MOLECULAR DOCKING","authors":"Irma Ratna Kartika, Teni Ernawati, S. A. Jusman, M. Sadikin","doi":"10.22159/ijap.2024v16i3.50040","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.50040","url":null,"abstract":"Objective: The goal of this study was to create vitamin E derivatives and explore their potential anticancer properties using a computational approach.\u0000Methods: The Steglich method was used for the synthesis of the vitamin E-fatty acid (pentanoic acid, heptanoic acid, and octanoic acid) derivatives, with N,N'-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) as the catalysts. The structure of the synthesized products was determined by ultraviolet-visible (UV-Vis) spectroscopy, fourier transform infrared (FTIR) spectroscopy, and liquid chromatography-mass spectrometry (LC-MS). Molecular docking was carried out on the succinate dehydrogenase (SDH) enzyme using AutoDockTools.\u0000Results: α–Tocopherol pentanoate (α–TP), α–tocopherol heptanoate (α–TH), and α–tocopherol octanoate (α–TO) were the three vitamin E derivatives synthesized in this study. Based on the results of molecular docking, the novel compounds (α–TP, α–TH, and α–TO) generated bond energies of-10.57,-9.61, and-9.20 kcal/mol, respectively.\u0000Conclusion: All newly synthesized compounds exhibited lower binding affinity values than α–tocopherol (α–T). This confirms that these compounds might not provide greater advantages than α-tocopherol in terms of inhibitory effects on mitochondrial complex II (CII).","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"50 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141003246","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}
Pub Date : 2024-05-07DOI: 10.22159/ijap.2024v16i3.50242
Chekkilla Bhargavi, P. Raghuveer
Objective: This study focuses on improving the delivery of Piribedil, a poorly soluble drug, to the brain through the nasal route using a nanosuspension in a nasal in-situ gel. Methods: The nanosuspension was prepared using the sonoprecipitation method. Quality-by-Design (QbD) principles were used to optimize both the formulation and process parameters. The optimal process parameters were determined as sonication time (7.09 min), sonication amplitude (83.44%), and infusion rate (2.41 mL/min) with a desirability value of 0.970. Results: The nanosuspension exhibited an average particle size ranging from 46.7 nm to 50.1 nm, and polydispersity index values between 0.393 and 0.425. Zeta potential values ranged from -33.78 ± 1.86 mV to -35.06 ± 2.12 mV, indicating favorable stability. FTIR studies revealed molecular interactions between Piribedil and stabilizers. XRPD and DSC analyses showed the transition from a crystalline to an amorphous state in the nanosuspension. Dissolution studies demonstrated significantly accelerated dissolution for the Piribedil nanosuspension, attributed to its nanosize and improved wettability. Stability assessments confirmed the robustness of the nanosuspension. Conclusion: This innovative approach offers potential solutions for drug solubility challenges and blood-brain barrier penetration, holding promise for effective brain-targeted treatments.
{"title":"ENHANCING NOSE- TO- BRAIN DELIVERY OF PIRIBEDIL: DEVELOPMENT OF A NANOSUSPENSION DISPERSED IN NASAL IN-SITU GELLING SYSTEM","authors":"Chekkilla Bhargavi, P. Raghuveer","doi":"10.22159/ijap.2024v16i3.50242","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.50242","url":null,"abstract":"Objective: This study focuses on improving the delivery of Piribedil, a poorly soluble drug, to the brain through the nasal route using a nanosuspension in a nasal in-situ gel.\u0000Methods: The nanosuspension was prepared using the sonoprecipitation method. Quality-by-Design (QbD) principles were used to optimize both the formulation and process parameters. The optimal process parameters were determined as sonication time (7.09 min), sonication amplitude (83.44%), and infusion rate (2.41 mL/min) with a desirability value of 0.970.\u0000Results: The nanosuspension exhibited an average particle size ranging from 46.7 nm to 50.1 nm, and polydispersity index values between 0.393 and 0.425. Zeta potential values ranged from -33.78 ± 1.86 mV to -35.06 ± 2.12 mV, indicating favorable stability. FTIR studies revealed molecular interactions between Piribedil and stabilizers. XRPD and DSC analyses showed the transition from a crystalline to an amorphous state in the nanosuspension. Dissolution studies demonstrated significantly accelerated dissolution for the Piribedil nanosuspension, attributed to its nanosize and improved wettability. Stability assessments confirmed the robustness of the nanosuspension.\u0000Conclusion: This innovative approach offers potential solutions for drug solubility challenges and blood-brain barrier penetration, holding promise for effective brain-targeted treatments.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"69 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141003375","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}
Pub Date : 2024-05-07DOI: 10.22159/ijap.2024v16i3.50079
Mohd Abdul Baqi, Koppula Jayanthi, Raman Rajeshkumar
Objective: Thymidylate Kinase (TMK) plays a crucial role in bacterial DNA synthesis by catalyzing the phosphorylation of Deoxythymidine Monophosphate (dTMP) to form Deoxythymidine Diphosphate (dTDP). Consequently, this enzyme emerges as a promising target for developing novel anti-cancer drugs. However, no anti-cancer drugs have been reported for this target until now. Methods: Ligands obtained from Benzylidene derivatives were examined for their potency by using molecular docking by glide module, Qikprop screening of Absorption, Distribution, Metabolism, and Excretion (ADME) study, and prime Molecular Mechanics in Generalized Bond Surface Area study (MM-GBSA) by binding free energy. Hereafter, a Molecular Dynamic (MD) simulation was performed at 100 ns to assess the stability of the potential ligand as a Human TMK (HaTMK) inhibitor. Results: These ten molecules showed good binding affinity and hydrogen and hydrophobic bond interactions with Arg150, Phe42, and Phe72 in the HaTMK enzyme (PDB id: 1E2D). Among them, trichloro-6-(((4-hydroxyphenyl)imino)methyl)phenol molecule had a high XP-docking score of (−7.87 kcal/mol), based on extra-precision data. Prime MM-GBSA studies also showed promising binding affinities i.e., ΔBind (-34.59 kcal/mol), ΔLipo (-13.92 kcal/mol), and ΔVdW (-34.42 kcal/mol). Arg76 and Phe72 residues maintained constant interactions with the ligand during Molecular Dynamics (MD) simulation. This ligand showed a potential binding affinity for the TMK target. Conclusion: The trichloro-6-(((4-hydroxyphenyl)imino)methyl)phenol ligand has active sites, namely benzene ring, benzylidene, and oxygen group, which actively participate in interaction with the protein of HaTMK, thus indicating good potential activity as the inhibitor of HaTMK to treat colon cancer.
{"title":"DESIGN FOR THE COLON CANCER INHIBITORS TARGETING THYMIDYLATE KINASE BY USING INSILICO STUDIES","authors":"Mohd Abdul Baqi, Koppula Jayanthi, Raman Rajeshkumar","doi":"10.22159/ijap.2024v16i3.50079","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.50079","url":null,"abstract":"Objective: Thymidylate Kinase (TMK) plays a crucial role in bacterial DNA synthesis by catalyzing the phosphorylation of Deoxythymidine Monophosphate (dTMP) to form Deoxythymidine Diphosphate (dTDP). Consequently, this enzyme emerges as a promising target for developing novel anti-cancer drugs. However, no anti-cancer drugs have been reported for this target until now.\u0000Methods: Ligands obtained from Benzylidene derivatives were examined for their potency by using molecular docking by glide module, Qikprop screening of Absorption, Distribution, Metabolism, and Excretion (ADME) study, and prime Molecular Mechanics in Generalized Bond Surface Area study (MM-GBSA) by binding free energy. Hereafter, a Molecular Dynamic (MD) simulation was performed at 100 ns to assess the stability of the potential ligand as a Human TMK (HaTMK) inhibitor.\u0000Results: These ten molecules showed good binding affinity and hydrogen and hydrophobic bond interactions with Arg150, Phe42, and Phe72 in the HaTMK enzyme (PDB id: 1E2D). Among them, trichloro-6-(((4-hydroxyphenyl)imino)methyl)phenol molecule had a high XP-docking score of (−7.87 kcal/mol), based on extra-precision data. Prime MM-GBSA studies also showed promising binding affinities i.e., ΔBind (-34.59 kcal/mol), ΔLipo (-13.92 kcal/mol), and ΔVdW (-34.42 kcal/mol). Arg76 and Phe72 residues maintained constant interactions with the ligand during Molecular Dynamics (MD) simulation. This ligand showed a potential binding affinity for the TMK target.\u0000Conclusion: The trichloro-6-(((4-hydroxyphenyl)imino)methyl)phenol ligand has active sites, namely benzene ring, benzylidene, and oxygen group, which actively participate in interaction with the protein of HaTMK, thus indicating good potential activity as the inhibitor of HaTMK to treat colon cancer.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"30 49","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141005288","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}
Pub Date : 2024-05-07DOI: 10.22159/ijap.2024v16i3.49358
L. R., R. Velmurugan
The main reason for morbidity and death globally is cancer, which has a complex pathophysiology. There are several traditional treatments for cancer, including chemotherapy, radiation therapy, targeted therapies, and immunotherapies. Multiple drug resistance, cytotoxicity, and lack of specificity pose significant challenges to cancer treatments. Molecular diagnostics and cancer treatment have been transformed by nanotechnology. For cancer treatment, nanoparticles (1–100 nm) are ideal because they are biocompatible, have low toxicity, excellent stability, high permeability, are precise and stable, and can deliver clear and accurate results. There are several main categories of nanoparticles. When it comes to the delivery of nanoparticle drugs, tumour characteristics and the tumour environment are considered. As well as providing advantages over conventional cancer treatments, nanoparticles prevent multidrug resistance, further overcoming their limitations. As new mechanisms are unravelled in studying multidrug resistance, nanoparticles are becoming more critical. Nano formulations have gained a new perspective on cancer treatment due to their many therapeutic applications. The number of approved nanodrugs has not increased significantly despite most research being conducted in vivo and in vitro. A review of nanoparticle oncological implications, targeting mechanisms, and approved nanotherapeutics is presented here. A current perspective on clinical translation is also provided, highlighting its advantages and challenges.
{"title":"A REVIEW OF NANOPARTICLE INNOVATIONS IN CANCER THERAPY: IMPLICATIONS, TARGETING MECHANISMS AND CLINICAL PROSPECTS","authors":"L. R., R. Velmurugan","doi":"10.22159/ijap.2024v16i3.49358","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.49358","url":null,"abstract":"The main reason for morbidity and death globally is cancer, which has a complex pathophysiology. There are several traditional treatments for cancer, including chemotherapy, radiation therapy, targeted therapies, and immunotherapies. Multiple drug resistance, cytotoxicity, and lack of specificity pose significant challenges to cancer treatments. Molecular diagnostics and cancer treatment have been transformed by nanotechnology. For cancer treatment, nanoparticles (1–100 nm) are ideal because they are biocompatible, have low toxicity, excellent stability, high permeability, are precise and stable, and can deliver clear and accurate results. There are several main categories of nanoparticles. When it comes to the delivery of nanoparticle drugs, tumour characteristics and the tumour environment are considered. As well as providing advantages over conventional cancer treatments, nanoparticles prevent multidrug resistance, further overcoming their limitations. As new mechanisms are unravelled in studying multidrug resistance, nanoparticles are becoming more critical. Nano formulations have gained a new perspective on cancer treatment due to their many therapeutic applications. The number of approved nanodrugs has not increased significantly despite most research being conducted in vivo and in vitro. A review of nanoparticle oncological implications, targeting mechanisms, and approved nanotherapeutics is presented here. A current perspective on clinical translation is also provided, highlighting its advantages and challenges.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"32 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141005315","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}
Pub Date : 2024-05-07DOI: 10.22159/ijap.2024v16i3.50382
Dhiya Altememy, Maryam Haji GHASEM KASHANI, Osamah N. WENAS
Objective: The widespread use of household electrical appliances generating electric and magnetic fields was a significant focus of WHO attention because of its serious threat to human health, especially osteogenesis. This research investigated the effect of 50 Hz frequency (1 mT intensity) sinusoidal EMF (SEMF) on the osteogenic differentiation of rat bone marrow stem cells (rBMSCs) in vitro. Methods: Experimental groups were: positive control (cells cultured in osteogenic medium supplemented with 7-10 M Dexamethasone, negative control (cells cultured in α-MEM/10% FBS, 10 mmol Beta-Glycerol-Phosphate, 15% FBS, 50 ug/ml Ascorbic Acid bi-Phosphate, 100 unit/ml Penicillin) and for the EMF group, cells exposed to SEMF (50 Hz, 1 mT, 30 min/day) for 14 and 21 d. Alizarin red staining, Alkaline phosphatase activity, and QRT-PCR were performed. Results: The EMF group exhibited weaker positive stains for ALP and Alizarin red than the positive control group. The Runx2 and Ocn gene expression levels were significantly decreased compared to negative control at 14 and 21 d of EMF exposure, respectively. After 14 and 21 d of exposure, Runx2 and Ocn gene expression were much lower in the EMF group than in the positive control group. Conclusion: SEMF (1 mT, 50 Hz, 30 min/day) could retarded osteogenesis and reduce the osteogenic differentiation of rBMSCs.
{"title":"SINUSOIDAL ELECTROMAGNETIC FIELD DECREASES OSTEOGENIC DIFFERENTIATION OF RAT BONE MARROW MESENCHYMAL STEM CELLS","authors":"Dhiya Altememy, Maryam Haji GHASEM KASHANI, Osamah N. WENAS","doi":"10.22159/ijap.2024v16i3.50382","DOIUrl":"https://doi.org/10.22159/ijap.2024v16i3.50382","url":null,"abstract":"Objective: The widespread use of household electrical appliances generating electric and magnetic fields was a significant focus of WHO attention because of its serious threat to human health, especially osteogenesis. This research investigated the effect of 50 Hz frequency (1 mT intensity) sinusoidal EMF (SEMF) on the osteogenic differentiation of rat bone marrow stem cells (rBMSCs) in vitro.\u0000Methods: Experimental groups were: positive control (cells cultured in osteogenic medium supplemented with 7-10 M Dexamethasone, negative control (cells cultured in α-MEM/10% FBS, 10 mmol Beta-Glycerol-Phosphate, 15% FBS, 50 ug/ml Ascorbic Acid bi-Phosphate, 100 unit/ml Penicillin) and for the EMF group, cells exposed to SEMF (50 Hz, 1 mT, 30 min/day) for 14 and 21 d. Alizarin red staining, Alkaline phosphatase activity, and QRT-PCR were performed.\u0000Results: The EMF group exhibited weaker positive stains for ALP and Alizarin red than the positive control group. The Runx2 and Ocn gene expression levels were significantly decreased compared to negative control at 14 and 21 d of EMF exposure, respectively. After 14 and 21 d of exposure, Runx2 and Ocn gene expression were much lower in the EMF group than in the positive control group.\u0000Conclusion: SEMF (1 mT, 50 Hz, 30 min/day) could retarded osteogenesis and reduce the osteogenic differentiation of rBMSCs.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"70 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141003366","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：