F. El‐Hag, Ahmed Elrashedy, Ayman M. K. Sweed, E. Ewies, M. Abd‐El‐Maksoud, M. Aly, S. Atta
Background The chemistry of condensed heterocyclic compounds has emerged in numerous reports for their diverse biological properties and drug discovery. Pyrimidine and triazine scaffolds have been utilized as therapeutic agents in many medicinal applications. Many research groups have designed and synthesized pyrimidine moieties as they are incorporated in nucleic acid bases. Objective In this report, we have designed and synthesized a variety of 2-mercaptothieno pyrimidine and thienotriazine derivatives and 2-mercaptothienopyrimidines conjugated with sugar moiety. The newly synthesized compounds were tested for their biological activity against breast (MCF-7), liver (HepG-2), and prostate (PC-3) cancer cell lines as well as a normal cell line (human normal melanocyte, HFB4) and were also analyzed for in silico studies to determine their potential. Materials and methods A variety of 2-mercaptothienopyrimidine and thienotriazine derivatives were prepared via cyclization of ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (1) and 2-amino-N-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (9). Two derivatives of 2-mercaptothienopyrimidines conjugated with sugar moiety were also prepared. The products were screened for their biological activity against breast (MCF-7), liver (HepG-2), and prostate (PC-3) cancer cell lines as well as the normal cell line (human normal melanocyte, HFB4) in comparison with the known anticancer drug 5-fluorouracil using the MTT assay. Results and conclusion The results indicated that most of the tested compounds exhibited no activity against the growth of HFB4. Compounds 5, 8, 10, 12, and 14 revealed effective antiproliferative activity against MCF-7 cell lines with IC50 of 4.6, 6.2, 5.4, 7, and 3.25 µg/ml, respectively, compared with 5-fluorouracil (IC50 of 3.97 µg/ml). In the same sense, the evaluation of cytotoxic effect of the tested compounds against human liver HepG-2 cancer cell lines revealed that compounds 5, 8, 10, 12, and 14 showed cytotoxic activity close to that of the standard drug (IC50 values of 5.77±0.99, 7.23±0.98, 4.42±1.32, 7.9±0.90, and 5.1±11.28 µg/ml, respectively, vs. 4.27±0.58 µg/ml for 5-fluorouracil). Free binding energy was estimated by docking and MM-GBSA calculation. Molecular dynamics simulation followed by MM-GBSA calculation was correlated to the cytotoxic effect. Compound 14 illustrated the highest MM-GBSA value (−20.38) and the best cytotoxic effect.
缩合杂环化合物的化学性质因其多样的生物学特性和药物发现而出现在许多报道中。嘧啶和三嗪支架在许多医学应用中被用作治疗剂。许多研究小组已经设计和合成了嘧啶部分，因为它们被纳入核酸碱基。目的设计并合成了多种2-巯基噻吩嘧啶和噻吩三嗪衍生物以及糖基偶联的2-巯基噻吩嘧啶。新合成的化合物对乳腺癌(MCF-7)、肝癌(HepG-2)和前列腺癌(PC-3)细胞系以及正常细胞系(人正常黑素细胞，HFB4)的生物活性进行了测试，并进行了计算机研究，以确定其潜力。材料与方法以2-氨基-4,5,6,7-四氢苯并[b]噻吩-3-羧酸乙酯(1)和2-氨基- n -苯基-4,5,6,7-四氢苯并[b]噻吩-3-羧酰胺(9)为环，制备了多种2-巯基噻吩-3-氨基嘧啶衍生物。使用MTT法筛选产品对乳腺癌(MCF-7)、肝癌(HepG-2)和前列腺癌(PC-3)细胞系以及正常细胞系(人正常黑素细胞，HFB4)的生物活性，并与已知的抗癌药物5-氟尿嘧啶进行比较。结果与结论大部分化合物对HFB4的生长无抑制作用。与5-氟尿嘧啶(IC50为3.97 μ g/ml)相比，化合物5、8、10、12和14对MCF-7细胞系显示出有效的抗增殖活性，IC50分别为4.6、6.2、5.4、7和3.25 μ g/ml。同样，化合物5、8、10、12、14对人肝脏HepG-2癌细胞的细胞毒作用评价表明，化合物5、8、10、12、14的细胞毒活性接近标准药物(IC50值分别为5.77±0.99、7.23±0.98、4.42±1.32、7.9±0.90、5.1±11.28µg/ml, 5-氟尿嘧啶为4.27±0.58µg/ml)。通过对接和MM-GBSA计算估计自由结合能。分子动力学模拟和MM-GBSA计算与细胞毒作用相关。化合物14的MM-GBSA值最高(−20.38)，细胞毒作用最好。
{"title":"Synthesis, biological activity, and in silico studies of thieno[2,3-d]pyrimidine and thieno[2,3-d]triazine derivatives","authors":"F. El‐Hag, Ahmed Elrashedy, Ayman M. K. Sweed, E. Ewies, M. Abd‐El‐Maksoud, M. Aly, S. Atta","doi":"10.4103/epj.epj_54_22","DOIUrl":"https://doi.org/10.4103/epj.epj_54_22","url":null,"abstract":"Background The chemistry of condensed heterocyclic compounds has emerged in numerous reports for their diverse biological properties and drug discovery. Pyrimidine and triazine scaffolds have been utilized as therapeutic agents in many medicinal applications. Many research groups have designed and synthesized pyrimidine moieties as they are incorporated in nucleic acid bases. Objective In this report, we have designed and synthesized a variety of 2-mercaptothieno pyrimidine and thienotriazine derivatives and 2-mercaptothienopyrimidines conjugated with sugar moiety. The newly synthesized compounds were tested for their biological activity against breast (MCF-7), liver (HepG-2), and prostate (PC-3) cancer cell lines as well as a normal cell line (human normal melanocyte, HFB4) and were also analyzed for in silico studies to determine their potential. Materials and methods A variety of 2-mercaptothienopyrimidine and thienotriazine derivatives were prepared via cyclization of ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (1) and 2-amino-N-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (9). Two derivatives of 2-mercaptothienopyrimidines conjugated with sugar moiety were also prepared. The products were screened for their biological activity against breast (MCF-7), liver (HepG-2), and prostate (PC-3) cancer cell lines as well as the normal cell line (human normal melanocyte, HFB4) in comparison with the known anticancer drug 5-fluorouracil using the MTT assay. Results and conclusion The results indicated that most of the tested compounds exhibited no activity against the growth of HFB4. Compounds 5, 8, 10, 12, and 14 revealed effective antiproliferative activity against MCF-7 cell lines with IC50 of 4.6, 6.2, 5.4, 7, and 3.25 µg/ml, respectively, compared with 5-fluorouracil (IC50 of 3.97 µg/ml). In the same sense, the evaluation of cytotoxic effect of the tested compounds against human liver HepG-2 cancer cell lines revealed that compounds 5, 8, 10, 12, and 14 showed cytotoxic activity close to that of the standard drug (IC50 values of 5.77±0.99, 7.23±0.98, 4.42±1.32, 7.9±0.90, and 5.1±11.28 µg/ml, respectively, vs. 4.27±0.58 µg/ml for 5-fluorouracil). Free binding energy was estimated by docking and MM-GBSA calculation. Molecular dynamics simulation followed by MM-GBSA calculation was correlated to the cytotoxic effect. Compound 14 illustrated the highest MM-GBSA value (−20.38) and the best cytotoxic effect.","PeriodicalId":11568,"journal":{"name":"Egyptian Pharmaceutical Journal","volume":"21 1","pages":"360 - 375"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46800750","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}
Background The traditional oral formulation for migraine treatment has the drawbacks of first-pass metabolism, plasma-protein binding, and poor blood–brain-barrier penetration. This study was conducted to establish the nasal route of administration for rizatriptan formulations in migraine. Materials and methods Rizatriptan mucoadhesive microparticles were synthesized by spray-drying and evaluated for infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. The ex vivo study was done with Franz’s diffusion cell using goat nasal mucosa. The in vivo study was performed on the Albino rat’s nasal route for determining drug concentration by high-performance liquid chromatography analysis in brain tissue at single-point evaluation. Result The microparticles were of optimum size with no drug–polymer interaction in infrared spectroscopy and differential scanning calorimetry. Scanning electron microscopy exhibited the morphology of spherical or ellipsoid microparticles with efficient drug entrapment. The percentage of drug permeability for chitosan microparticles was 76.53–91.09 and for carbopol microparticles was 78.49–92.25 in the ex vivo permeability study. In vivo studies showed that drug concentrations of 126.46–148.50% for chitosan batches and 152.83–165.04% for carbopol batches were superior to controls. Conclusion Ex vivo permeability study revealed drug-permeation patterns as high as 91.09±0.03% for RCH3 formulation and 92.25±0.2% for RC3 formulation. In in vivo study formulation, RCH3 displayed a drug concentration of 132.22±8.32% and RC3 showed 159.46±4.05% over the control batch, which is conclusive for improved drug delivery of rizatriptan through mucoadhesive microparticles for the nose-to-brain targeting in migraine.
{"title":"The spray-dried mucoadhesive microparticles of rizatriptan with chitosan and carbopol in migraine","authors":"Sachin B. Jadhav, S. Mishra","doi":"10.4103/epj.epj_37_22","DOIUrl":"https://doi.org/10.4103/epj.epj_37_22","url":null,"abstract":"Background The traditional oral formulation for migraine treatment has the drawbacks of first-pass metabolism, plasma-protein binding, and poor blood–brain-barrier penetration. This study was conducted to establish the nasal route of administration for rizatriptan formulations in migraine. Materials and methods Rizatriptan mucoadhesive microparticles were synthesized by spray-drying and evaluated for infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. The ex vivo study was done with Franz’s diffusion cell using goat nasal mucosa. The in vivo study was performed on the Albino rat’s nasal route for determining drug concentration by high-performance liquid chromatography analysis in brain tissue at single-point evaluation. Result The microparticles were of optimum size with no drug–polymer interaction in infrared spectroscopy and differential scanning calorimetry. Scanning electron microscopy exhibited the morphology of spherical or ellipsoid microparticles with efficient drug entrapment. The percentage of drug permeability for chitosan microparticles was 76.53–91.09 and for carbopol microparticles was 78.49–92.25 in the ex vivo permeability study. In vivo studies showed that drug concentrations of 126.46–148.50% for chitosan batches and 152.83–165.04% for carbopol batches were superior to controls. Conclusion Ex vivo permeability study revealed drug-permeation patterns as high as 91.09±0.03% for RCH3 formulation and 92.25±0.2% for RC3 formulation. In in vivo study formulation, RCH3 displayed a drug concentration of 132.22±8.32% and RC3 showed 159.46±4.05% over the control batch, which is conclusive for improved drug delivery of rizatriptan through mucoadhesive microparticles for the nose-to-brain targeting in migraine.","PeriodicalId":11568,"journal":{"name":"Egyptian Pharmaceutical Journal","volume":"21 1","pages":"293 - 301"},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42437850","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}
M. Nayan, M. Alam, M. Jamil, J. Hannan, Iqramul Haq, M. Hossain
Background and objective Cinnamomum verum bark is locally known as ‘Daruchini’ and is traditionally reputed as an Ayurvedic medicine, which is used in the treatment of flatulence, toothache, heart diseases, fever, cough, cold, headache, and many others. In this study, we intended to explore the effectiveness of its activity on hyperglycemia. Materials and methods To evaluate its antihyperglycemic activity, we used various experimental designs, including the effect of plant extract on gastrointestinal (GI) motility in the Swiss albino mice model and intestinal disaccharidase enzyme activity and carbohydrate digestion and absorption in the gut of the Long Evans rats. Results and discussion The plant extract significantly (P<0.001) increased the GI motility rate by ∼16% than the control (distilled water, 10 ml/kg body weight) and indicated that it interfered with the rate of glucose absorption in the gut. Furthermore, treatment with C. verum caused a significant (P<0.05) dose-dependent reduction of intestinal disaccharidase enzyme activity from 1.63 to 1.21 µmol/mg protein/h in fasting Long Evans rats. Besides, the extract produced a similar effect in the acute oral sucrose (2.5 g/kg body weight) load assay, in which a substantial amount of unabsorbed sucrose was found in six different parts of the GI tract after sucrose administration. This indicates that C. verum can liberate GI content and reduce or delay glucose absorption. Conclusion All the findings of the present study point to the conclusion that C. verum has the potential to exert postprandial antihyperglycemic activity within type 2 diabetic animal models through reducing or delaying carbohydrate digestion and absorption in the gut.
{"title":"An in-vivo study on postprandial hyperglycemia to assess antidiabetic activity of alcoholic extract of Cinnamomum verum bark","authors":"M. Nayan, M. Alam, M. Jamil, J. Hannan, Iqramul Haq, M. Hossain","doi":"10.4103/epj.epj_102_21","DOIUrl":"https://doi.org/10.4103/epj.epj_102_21","url":null,"abstract":"Background and objective Cinnamomum verum bark is locally known as ‘Daruchini’ and is traditionally reputed as an Ayurvedic medicine, which is used in the treatment of flatulence, toothache, heart diseases, fever, cough, cold, headache, and many others. In this study, we intended to explore the effectiveness of its activity on hyperglycemia. Materials and methods To evaluate its antihyperglycemic activity, we used various experimental designs, including the effect of plant extract on gastrointestinal (GI) motility in the Swiss albino mice model and intestinal disaccharidase enzyme activity and carbohydrate digestion and absorption in the gut of the Long Evans rats. Results and discussion The plant extract significantly (P<0.001) increased the GI motility rate by ∼16% than the control (distilled water, 10 ml/kg body weight) and indicated that it interfered with the rate of glucose absorption in the gut. Furthermore, treatment with C. verum caused a significant (P<0.05) dose-dependent reduction of intestinal disaccharidase enzyme activity from 1.63 to 1.21 µmol/mg protein/h in fasting Long Evans rats. Besides, the extract produced a similar effect in the acute oral sucrose (2.5 g/kg body weight) load assay, in which a substantial amount of unabsorbed sucrose was found in six different parts of the GI tract after sucrose administration. This indicates that C. verum can liberate GI content and reduce or delay glucose absorption. Conclusion All the findings of the present study point to the conclusion that C. verum has the potential to exert postprandial antihyperglycemic activity within type 2 diabetic animal models through reducing or delaying carbohydrate digestion and absorption in the gut.","PeriodicalId":11568,"journal":{"name":"Egyptian Pharmaceutical Journal","volume":"21 1","pages":"187 - 191"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41825576","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}
Shimaa Elswaby, M. Sadik, A. Azouz, N. Emam, Mohamed Ali
Background and objective Honeybee products are commonly used as food and medicine. Recently, pharmacological properties of bee venom and propolis have been reported. However, the geographic origin of bee venom and propolis influences their chemical composition and biological activities. The antimicrobial and antioxidant properties of bee venom and propolis collected from different regions in Egypt were evaluated. Materials and methods Bee venom and propolis were collected from the regions of Kafr-Elsheikh, Fayoum, and Giza in Egypt. The antimicrobial and antioxidant effects of bee venom and propolis extracts obtained with various solvents were evaluated using the well-diffusion method and the 1,1-diphenyl-2-picrilidrazil free radical scavenging assay, respectively. Results and conclusion The antimicrobial activities of bee venom extracts were greater than those of propolis extracts, and ethanol extracts were more efficient than chloroform and water extracts. Extracts obtained from the Kafr-Elsheikh region were the most active, whereas those from the Giza region were less effective. Gram-positive bacteria were more sensitive than gram-negative bacteria and fungi. Propolis extracts were more effective antioxidants than bee venom extracts. The activities of extracts from the Kafr-Elsheikh or the Fayoum regions were comparable and greater than those of the corresponding extracts from the Giza region. Ethanolic extraction provided the greatest antioxidant potential. The biological activity of Egyptian bee venom or propolis varies significantly depending on the extraction solvent and geographical area of collection. These results provide insights into the antimicrobial and antioxidant properties of Egyptian bee venom and propolis and constitute a basis for further phytochemical and pharmacological research.
{"title":"In vitro evaluation of antimicrobial and antioxidant activities of honeybee venom and propolis collected from various regions in Egypt","authors":"Shimaa Elswaby, M. Sadik, A. Azouz, N. Emam, Mohamed Ali","doi":"10.4103/epj.epj_18_22","DOIUrl":"https://doi.org/10.4103/epj.epj_18_22","url":null,"abstract":"Background and objective Honeybee products are commonly used as food and medicine. Recently, pharmacological properties of bee venom and propolis have been reported. However, the geographic origin of bee venom and propolis influences their chemical composition and biological activities. The antimicrobial and antioxidant properties of bee venom and propolis collected from different regions in Egypt were evaluated. Materials and methods Bee venom and propolis were collected from the regions of Kafr-Elsheikh, Fayoum, and Giza in Egypt. The antimicrobial and antioxidant effects of bee venom and propolis extracts obtained with various solvents were evaluated using the well-diffusion method and the 1,1-diphenyl-2-picrilidrazil free radical scavenging assay, respectively. Results and conclusion The antimicrobial activities of bee venom extracts were greater than those of propolis extracts, and ethanol extracts were more efficient than chloroform and water extracts. Extracts obtained from the Kafr-Elsheikh region were the most active, whereas those from the Giza region were less effective. Gram-positive bacteria were more sensitive than gram-negative bacteria and fungi. Propolis extracts were more effective antioxidants than bee venom extracts. The activities of extracts from the Kafr-Elsheikh or the Fayoum regions were comparable and greater than those of the corresponding extracts from the Giza region. Ethanolic extraction provided the greatest antioxidant potential. The biological activity of Egyptian bee venom or propolis varies significantly depending on the extraction solvent and geographical area of collection. These results provide insights into the antimicrobial and antioxidant properties of Egyptian bee venom and propolis and constitute a basis for further phytochemical and pharmacological research.","PeriodicalId":11568,"journal":{"name":"Egyptian Pharmaceutical Journal","volume":"21 1","pages":"207 - 213"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44679965","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}
Nada Mohamed, Amr E Ahmed, O. Azmy, S. Kamel, K. Hashem
Background and objectives Follicle-stimulating hormone (FSH) is critical for the onset and duration of follicular development. This can be promoted medically by drugs such as follitropin beta and recombinant follicle-stimulating hormone (rFSH) technology. The former is purified from CHO cell culture supernatant (111 amino acid) and has a high biochemical purity (>99%), with specific biological activity (about 10 000 IU/mg protein), and no luteinizing hormone activity. The drugs used for ovulation induction during in vitro fertilization may affect the number and quality of follicles produced. This in turn may affect the quality and the integrity of the embryos generated. Bad-quality embryos may cause recurrent pregnancy failure. We aimed to assess the relationship of urinary follicle-stimulating hormone (uFSH) versus recombinant follicle-stimulating hormone (rFSH) drugs in producing embryos with chromosomal abnormalities. Patients and methods Seven women were enrolled for the intracytoplasmic sperm injection trial: Three had highly purified uFSH and four had rFSH. All embryos had blastomere extraction on day 3 after injection but the preimplantation genetic screening was carried out 6 weeks after embryo transfer. Only one embryo was transferred to each woman. Results and conclusion The results revealed that there was no difference between the two drugs in terms of number and quality of embryos fertilized or abnormal karyotype assessed. Overall, 71% of the women included had some form of chromosomal abnormality (4/7). However, two of them miscarried between 2 and 3 weeks later. Either of uFSH or rFSH did not improve the quality or integrity of the embryos. However, preimplantation genetic screening is a valuable tool in the selection of embryos in assisted conception cycles to increase the take-home baby rate.
{"title":"Urinary follicle-stimulating hormone is not different than recombinant follicle-stimulating hormone on embryo quality and karyotype makeup during induction of ovulation in women with recurrent pregnancy failure","authors":"Nada Mohamed, Amr E Ahmed, O. Azmy, S. Kamel, K. Hashem","doi":"10.4103/epj.epj_74_21","DOIUrl":"https://doi.org/10.4103/epj.epj_74_21","url":null,"abstract":"Background and objectives Follicle-stimulating hormone (FSH) is critical for the onset and duration of follicular development. This can be promoted medically by drugs such as follitropin beta and recombinant follicle-stimulating hormone (rFSH) technology. The former is purified from CHO cell culture supernatant (111 amino acid) and has a high biochemical purity (>99%), with specific biological activity (about 10 000 IU/mg protein), and no luteinizing hormone activity. The drugs used for ovulation induction during in vitro fertilization may affect the number and quality of follicles produced. This in turn may affect the quality and the integrity of the embryos generated. Bad-quality embryos may cause recurrent pregnancy failure. We aimed to assess the relationship of urinary follicle-stimulating hormone (uFSH) versus recombinant follicle-stimulating hormone (rFSH) drugs in producing embryos with chromosomal abnormalities. Patients and methods Seven women were enrolled for the intracytoplasmic sperm injection trial: Three had highly purified uFSH and four had rFSH. All embryos had blastomere extraction on day 3 after injection but the preimplantation genetic screening was carried out 6 weeks after embryo transfer. Only one embryo was transferred to each woman. Results and conclusion The results revealed that there was no difference between the two drugs in terms of number and quality of embryos fertilized or abnormal karyotype assessed. Overall, 71% of the women included had some form of chromosomal abnormality (4/7). However, two of them miscarried between 2 and 3 weeks later. Either of uFSH or rFSH did not improve the quality or integrity of the embryos. However, preimplantation genetic screening is a valuable tool in the selection of embryos in assisted conception cycles to increase the take-home baby rate.","PeriodicalId":11568,"journal":{"name":"Egyptian Pharmaceutical Journal","volume":"21 1","pages":"124 - 133"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41957575","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}
Eid Hanafy, M. Ragab, Marwa Zayton, F. Abd-El-Kareem, H. Abouelnasr
Background Evaluation of preharvest application with some essential oils (EOs) for controlling gray mold disease of strawberry plants was studied. Objective In vitro trails, five EOs, that is, thyme, nerol, citral, methyl anthranilate, and clove oils, were evaluated for their capability to suppress fungal growth of Botrytis cinerea. At the National Center for Biotechnology Information, alignment showed the percentage of identity (100%) of B. cinerea between our isolates and Gene bank isolate. Materials and methods Five EOs were evaluated for their capability to suppress fungal linear growth of B. cinerea. Certain volume of each oil was added to autoclaved potato dextrose agar medium flasks to obtain the proposed concentrations of 00.0, 0.25, 0.5, and 1.0% with 0.1% Tween-80. Molecular identification using the internal transcribed spacer (ITS) region of rRNA Trimmed sequences (ITS 573 bp) was conducted. Results and conclusion B. cinerea isolate no. 3 was identified molecular using the ITS region of rRNA Trimmed sequences (ITS 573 bp) compared with different isolates of B. cinerea. All tested oils significantly reduced linear growth of B. cinerea fungus. Complete inhibition was obtained with concentration of 1.0% with all tested EOs and at 0.5% with thyme, citral, and methyl anthranilate, whereas concentration 0.25% showed moderate effect. Moreover, in vivo trails all tested EOs treatments at concentration of 0.5% significantly reduced disease incidence under natural infection. The most effective treatments are citral, methyl anthranilate, and thyme that reduced the disease incidence by 64.3%, 67.9%, and 67.9% on average at 5°C and 75.8%, 82.3%, and77.4% on average at 20°C, respectively, whereas other treatments showed moderate effect. The same trend was observed with disease severity. Meanwhile, under artificial infection, the highest reduction was obtained with citral, methyl anthranilate, and thyme that reduced the disease incidence by 68.2%, 75.0%, and 68.0% at 5°C and 76.0%, 77.0%, and 78.0% on average at 20°C, respectively. However, other treatments showed moderate effect. The same trend was observed with disease severity. As for fruit quality, all tested treatment had no negative effect on all tested characters of fruit quality. The most effective treatments are citral, methyl anthranilate, and thyme that reduced the decay incidence by 71.0%, 71.0%, and 69.3% and weight loss percentage by 79.4%, 78.2%, and 78.8%, respectively. Also, other treatments showed moderate effect, whereas methyl anthranilate, followed by thyme and clove increased the total soluble solid by 56.9%, 41.4%, and 36.2%, respectively. As for total soluble phenol, the highest increase was obtained with all tested oils. As for, titratable acidity, there are no significant differences between all tested treatments as compared with control fruits.
背景:研究了采前施用几种精油防治草莓灰霉病的效果评价。目的对百里香、橙花醇、柠檬醛、甲酰苯甲酸酯和丁香油5种精油进行体外抑菌试验，研究其抑菌效果。在国家生物技术信息中心(National Center for Biotechnology Information)的比对显示，我们的分离株与基因库分离株的同源率为100%。材料与方法研究了5种精油对灰绿杆菌线性生长的抑制作用。将每种油加入一定体积的高压马铃薯葡萄糖琼脂培养皿中，以获得建议的浓度为00.0,0.25,0.5和1.0%，0.1%吐温-80。利用rRNA修剪序列(ITS 573 bp)的内部转录间隔区(ITS)进行分子鉴定。结果与结论绿僵杆菌分离株;利用rRNA修剪序列的ITS区(ITS 573 bp)对3进行了分子鉴定，并与不同菌株进行了比较。所有被试油均能显著降低灰葡萄球菌的线性生长。浓度为1.0%和0.5%时，百里香、柠檬醛和甲酰苯甲酸甲酯均有完全抑制作用，而浓度为0.25%时，效果中等。此外，在体内试验中，浓度为0.5%的EOs治疗显著降低了自然感染下的疾病发病率。最有效的处理是柠檬醛、甲酰苯甲酸和百里香，在5°C时平均降低发病率64.3%、67.9%和67.9%，在20°C时平均降低发病率75.8%、82.3%和77.4%，而其他处理效果一般。疾病严重程度也有同样的趋势。同时，在人工感染下，柠檬醛、甲酰苯甲酸和百里香的降低率最高，在5°C时平均降低68.2%、75.0%和68.0%，在20°C时平均降低76.0%、77.0%和78.0%。然而，其他治疗效果一般。疾病严重程度也有同样的趋势。在果实品质方面，所有试验处理对果实品质的所有试验性状均无负面影响。柠檬醛、甲酰苯甲酸和百里香的处理效果最好，分别降低71.0%、71.0%和69.3%的蛀牙率和79.4%、78.2%和78.8%的减重率。其他处理对土壤可溶性固形物的处理效果也较好，其中，甲酰苯甲酸、百里香和丁香处理对土壤可溶性固形物总量的影响分别为56.9%、41.4%和36.2%。在总可溶性酚含量方面，所有被试油的增幅均最高。在可滴定酸度方面，各处理与对照相比无显著差异。
{"title":"Management of strawberry gray mold disease using some essential oils and molecular identification of pathogen fungus","authors":"Eid Hanafy, M. Ragab, Marwa Zayton, F. Abd-El-Kareem, H. Abouelnasr","doi":"10.4103/epj.epj_34_22","DOIUrl":"https://doi.org/10.4103/epj.epj_34_22","url":null,"abstract":"Background Evaluation of preharvest application with some essential oils (EOs) for controlling gray mold disease of strawberry plants was studied. Objective In vitro trails, five EOs, that is, thyme, nerol, citral, methyl anthranilate, and clove oils, were evaluated for their capability to suppress fungal growth of Botrytis cinerea. At the National Center for Biotechnology Information, alignment showed the percentage of identity (100%) of B. cinerea between our isolates and Gene bank isolate. Materials and methods Five EOs were evaluated for their capability to suppress fungal linear growth of B. cinerea. Certain volume of each oil was added to autoclaved potato dextrose agar medium flasks to obtain the proposed concentrations of 00.0, 0.25, 0.5, and 1.0% with 0.1% Tween-80. Molecular identification using the internal transcribed spacer (ITS) region of rRNA Trimmed sequences (ITS 573 bp) was conducted. Results and conclusion B. cinerea isolate no. 3 was identified molecular using the ITS region of rRNA Trimmed sequences (ITS 573 bp) compared with different isolates of B. cinerea. All tested oils significantly reduced linear growth of B. cinerea fungus. Complete inhibition was obtained with concentration of 1.0% with all tested EOs and at 0.5% with thyme, citral, and methyl anthranilate, whereas concentration 0.25% showed moderate effect. Moreover, in vivo trails all tested EOs treatments at concentration of 0.5% significantly reduced disease incidence under natural infection. The most effective treatments are citral, methyl anthranilate, and thyme that reduced the disease incidence by 64.3%, 67.9%, and 67.9% on average at 5°C and 75.8%, 82.3%, and77.4% on average at 20°C, respectively, whereas other treatments showed moderate effect. The same trend was observed with disease severity. Meanwhile, under artificial infection, the highest reduction was obtained with citral, methyl anthranilate, and thyme that reduced the disease incidence by 68.2%, 75.0%, and 68.0% at 5°C and 76.0%, 77.0%, and 78.0% on average at 20°C, respectively. However, other treatments showed moderate effect. The same trend was observed with disease severity. As for fruit quality, all tested treatment had no negative effect on all tested characters of fruit quality. The most effective treatments are citral, methyl anthranilate, and thyme that reduced the decay incidence by 71.0%, 71.0%, and 69.3% and weight loss percentage by 79.4%, 78.2%, and 78.8%, respectively. Also, other treatments showed moderate effect, whereas methyl anthranilate, followed by thyme and clove increased the total soluble solid by 56.9%, 41.4%, and 36.2%, respectively. As for total soluble phenol, the highest increase was obtained with all tested oils. As for, titratable acidity, there are no significant differences between all tested treatments as compared with control fruits.","PeriodicalId":11568,"journal":{"name":"Egyptian Pharmaceutical Journal","volume":"21 1","pages":"223 - 232"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47027905","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}
H. Modir, Behnam Mahmoodiyeh, Mehran Azami, Armita Behnamimoghadam, A. Almasi-Hashiani
Background The effectiveness of postoperative pain relief regimens is well established and postulated to rely on diverse factors. Objective The aim of this study was to compare the effect of gabapentin and melatonin and dextromethorphan on postoperative pain control in patients undergoing hip fracture surgery under general anesthesia. Patients and methods In a double-blind controlled trial 125 patients requiring hip fracture surgery enrollment into the study after following ethical approval and informed participant consent. The patients were randomized to either each of the three regimens (gabapentin, melatonin, and dextromethorphan) by the block-randomization method. Outcome measurements were of foremost importance, patient’s pain scores throughout the recovery time and scheduled postoperative time intervals (2, 4, 6, 12, 24 h), doses of opioid use (mg) in the initial 24 h, and at length, sedation levels using the Ramsay scoring system at the early postoperative time intervals. Moreover, complications including chills, nausea, vomiting, and decreased consciousness were recorded. Statistical data analysis conducted by analysis of variance, χ2, and repeated measurements through SPSS, version 20. Results Gabapentin-treated patients manifested the lowest blood pressures (P<0.05), with maximum pain relief being experienced, sedation level being greater (P<0.05), and opioid use being lower in the group (P=0.0001). Conclusion We have the impression that gabapentin could be connected with improving pain relief and sedation, whereas opioid use was observed comparatively lower in the initial 24 h, and hence inferentially. The premedication can be driven to be superior in creating favorable conditions for analgesia and sedation and effective in preventing complications requiring treatment within 24 h postoperatively versus baseline and promisingly suggested to be continued for postoperative pain management, procedural sedation quality improvement, and opioid use reduction within the initial 24 h.
{"title":"Comparative premedication efficacy of gabapentin, melatonin, and dextromethorphan in postoperative pain management following general anesthesia in hip fracture surgery: a randomized clinical trial","authors":"H. Modir, Behnam Mahmoodiyeh, Mehran Azami, Armita Behnamimoghadam, A. Almasi-Hashiani","doi":"10.4103/epj.epj_61_21","DOIUrl":"https://doi.org/10.4103/epj.epj_61_21","url":null,"abstract":"Background The effectiveness of postoperative pain relief regimens is well established and postulated to rely on diverse factors. Objective The aim of this study was to compare the effect of gabapentin and melatonin and dextromethorphan on postoperative pain control in patients undergoing hip fracture surgery under general anesthesia. Patients and methods In a double-blind controlled trial 125 patients requiring hip fracture surgery enrollment into the study after following ethical approval and informed participant consent. The patients were randomized to either each of the three regimens (gabapentin, melatonin, and dextromethorphan) by the block-randomization method. Outcome measurements were of foremost importance, patient’s pain scores throughout the recovery time and scheduled postoperative time intervals (2, 4, 6, 12, 24 h), doses of opioid use (mg) in the initial 24 h, and at length, sedation levels using the Ramsay scoring system at the early postoperative time intervals. Moreover, complications including chills, nausea, vomiting, and decreased consciousness were recorded. Statistical data analysis conducted by analysis of variance, χ2, and repeated measurements through SPSS, version 20. Results Gabapentin-treated patients manifested the lowest blood pressures (P<0.05), with maximum pain relief being experienced, sedation level being greater (P<0.05), and opioid use being lower in the group (P=0.0001). Conclusion We have the impression that gabapentin could be connected with improving pain relief and sedation, whereas opioid use was observed comparatively lower in the initial 24 h, and hence inferentially. The premedication can be driven to be superior in creating favorable conditions for analgesia and sedation and effective in preventing complications requiring treatment within 24 h postoperatively versus baseline and promisingly suggested to be continued for postoperative pain management, procedural sedation quality improvement, and opioid use reduction within the initial 24 h.","PeriodicalId":11568,"journal":{"name":"Egyptian Pharmaceutical Journal","volume":"21 1","pages":"117 - 123"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45473393","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}
H. El Menoufy, Sanaa K. Gomaa, A. Haroun, A. Farag, M. Shafei, Y. Shetaia, R. Abd El Aal
Background and objective Lipases (triacylglycerol acylhydrolase, EC. 3.1.1.3) belong to a class of hydrolases that are specific for the hydrolysis of fats into fatty acids and glycerol that have much application in different industrial processes. Fungi, yeast, and bacteria have been reported to be sources of lipase. There are many immobilized methods for enzyme, and the commonly used methods are physical adsorption, entrapment, and cross-linkage. This study aimed to evaluate lipase production by Aspergillus niger NRRL-599 in solid cultivation using agro-industrial waste as a substrate. Partial purification of the crude enzyme and its characterization and immobilization using nanoparticles were carried out. The potential application of the immobilized and partially purified enzyme was also studied in the field of textile. Materials and methods Partially purified A. niger NRRL-599 lipase was immobilized by physical adsorption onto modified titanium dioxide nanoparticles using gelatin and palmitic acid binders and characterized by transmission electron microscopy, dynamic light scattering, and Fourier-transform infrared. Results and conclusion In our study, lipase produced by A. niger NRRL-599 was partially purified by ammonium sulfate at 60% saturation and immobilized on gelatin-coated titanium dioxide. Comparison between the properties of the free and the immobilized A. niger NRRL-599 lipase forms was carried out. The optimum pH was 9.0 and 10.0 for the free and immobilized forms, respectively. The half-life of the soluble-free lipase at 50 and 55°C was 17.3 and 23.1 min, respectively, whereas for the immobilized form was 23.1 and 34.6 min, respectively. At 50 and 55°C, the deactivation rate constants (kD) for soluble lipase were 6.6×10−3 and 5×10−3, respectively, and 6.6×10−3 and 3.3×10−3, respectively, for immobilized lipase. The Km was 11.11 and 12.5 mM for the immobilized and free forms, respectively. The Vmax was 416.6 U/mg protein and 296.3 U/mg protein for immobilized and free lipase forms, respectively. This confirms that the apparent affinity toward the substrate increases by immobilization. Partially purified lipase and immobilized enzymes were used in the textiles in the treatment of wool fibers before dying to improve the color strength.
{"title":"Comparative studies of free and immobilized partially purified lipase from Aspergillus niger NRRL-599 produced from solid-state fermentation using gelatin-coated titanium nanoparticles and its application in textile industry","authors":"H. El Menoufy, Sanaa K. Gomaa, A. Haroun, A. Farag, M. Shafei, Y. Shetaia, R. Abd El Aal","doi":"10.4103/epj.epj_90_21","DOIUrl":"https://doi.org/10.4103/epj.epj_90_21","url":null,"abstract":"Background and objective Lipases (triacylglycerol acylhydrolase, EC. 3.1.1.3) belong to a class of hydrolases that are specific for the hydrolysis of fats into fatty acids and glycerol that have much application in different industrial processes. Fungi, yeast, and bacteria have been reported to be sources of lipase. There are many immobilized methods for enzyme, and the commonly used methods are physical adsorption, entrapment, and cross-linkage. This study aimed to evaluate lipase production by Aspergillus niger NRRL-599 in solid cultivation using agro-industrial waste as a substrate. Partial purification of the crude enzyme and its characterization and immobilization using nanoparticles were carried out. The potential application of the immobilized and partially purified enzyme was also studied in the field of textile. Materials and methods Partially purified A. niger NRRL-599 lipase was immobilized by physical adsorption onto modified titanium dioxide nanoparticles using gelatin and palmitic acid binders and characterized by transmission electron microscopy, dynamic light scattering, and Fourier-transform infrared. Results and conclusion In our study, lipase produced by A. niger NRRL-599 was partially purified by ammonium sulfate at 60% saturation and immobilized on gelatin-coated titanium dioxide. Comparison between the properties of the free and the immobilized A. niger NRRL-599 lipase forms was carried out. The optimum pH was 9.0 and 10.0 for the free and immobilized forms, respectively. The half-life of the soluble-free lipase at 50 and 55°C was 17.3 and 23.1 min, respectively, whereas for the immobilized form was 23.1 and 34.6 min, respectively. At 50 and 55°C, the deactivation rate constants (kD) for soluble lipase were 6.6×10−3 and 5×10−3, respectively, and 6.6×10−3 and 3.3×10−3, respectively, for immobilized lipase. The Km was 11.11 and 12.5 mM for the immobilized and free forms, respectively. The Vmax was 416.6 U/mg protein and 296.3 U/mg protein for immobilized and free lipase forms, respectively. This confirms that the apparent affinity toward the substrate increases by immobilization. Partially purified lipase and immobilized enzymes were used in the textiles in the treatment of wool fibers before dying to improve the color strength.","PeriodicalId":11568,"journal":{"name":"Egyptian Pharmaceutical Journal","volume":"21 1","pages":"143 - 152"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70734699","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}
H. Raouf, N. Kholoussi, S. Kholoussi, Assem Abo-Shanab
Background Autism spectrum disorder (ASD) is considered a spectrum of behavioral anomalies described by having impaired social interaction and communication. It is usually accompanied by repetitive and stereotyped behavior. ASD likely develops from a combination of genetic and environmental factors. Among suggestions, one has been persistently proposed where an immune dysfunction was related to certain forms of ASD. Growing evidence of autoimmune phenomena in patients with ASD may represent the occurrence of changed or perhaps unsuitable immune responses in this disorder. Objectives This study was aimed to evaluate cell-mediated as well as humoral immunity in children with ASD. This was through evaluation of lymphocyte count (CD3, CD16, and CD19) and estimation of the serum immunoglobulin levels (IgG, IgM, and IgA). Patients and methods This study was carried out in the National Research Centre. A total of 50 newly diagnosed children with ASD were included (33 males and 17 females), with an age range from 3 to 8 years, in addition to 50 apparently healthy age-matched and sex-matched participants as a control group. CD3, CD16, and CD19 were estimated using flow cytometry. Serum Ig levels were measured using immunonephelometry. Results and conclusion The study results revealed that children with autism had significantly lower CD19 in comparison with the control group (P<0.001). Autistic children also had considerably higher numbers of CD16 (P<0.001) and significant increased absolute lymphocyte count (P=0.034) in comparison with healthy controls. CD3% and absolute CD16 count were significantly positive correlated with Childhood Autism Rating Scale score in children with ASD (P=0.004 and 0.025, respectively). An increased total lymphocyte and natural killer cell count together with decreased B lymphocyte count and positive correlations in CD3 and absolute CD16 count with Childhood Autism Rating Scale score in participants with ASD revealed the impaired cell-mediated immunity in participants with ASD, and these tests might be useful as diagnostic markers for ASD and its degree of severity.
{"title":"Association of immune abnormalities with symptom severity in Egyptian autistic children","authors":"H. Raouf, N. Kholoussi, S. Kholoussi, Assem Abo-Shanab","doi":"10.4103/epj.epj_32_22","DOIUrl":"https://doi.org/10.4103/epj.epj_32_22","url":null,"abstract":"Background Autism spectrum disorder (ASD) is considered a spectrum of behavioral anomalies described by having impaired social interaction and communication. It is usually accompanied by repetitive and stereotyped behavior. ASD likely develops from a combination of genetic and environmental factors. Among suggestions, one has been persistently proposed where an immune dysfunction was related to certain forms of ASD. Growing evidence of autoimmune phenomena in patients with ASD may represent the occurrence of changed or perhaps unsuitable immune responses in this disorder. Objectives This study was aimed to evaluate cell-mediated as well as humoral immunity in children with ASD. This was through evaluation of lymphocyte count (CD3, CD16, and CD19) and estimation of the serum immunoglobulin levels (IgG, IgM, and IgA). Patients and methods This study was carried out in the National Research Centre. A total of 50 newly diagnosed children with ASD were included (33 males and 17 females), with an age range from 3 to 8 years, in addition to 50 apparently healthy age-matched and sex-matched participants as a control group. CD3, CD16, and CD19 were estimated using flow cytometry. Serum Ig levels were measured using immunonephelometry. Results and conclusion The study results revealed that children with autism had significantly lower CD19 in comparison with the control group (P<0.001). Autistic children also had considerably higher numbers of CD16 (P<0.001) and significant increased absolute lymphocyte count (P=0.034) in comparison with healthy controls. CD3% and absolute CD16 count were significantly positive correlated with Childhood Autism Rating Scale score in children with ASD (P=0.004 and 0.025, respectively). An increased total lymphocyte and natural killer cell count together with decreased B lymphocyte count and positive correlations in CD3 and absolute CD16 count with Childhood Autism Rating Scale score in participants with ASD revealed the impaired cell-mediated immunity in participants with ASD, and these tests might be useful as diagnostic markers for ASD and its degree of severity.","PeriodicalId":11568,"journal":{"name":"Egyptian Pharmaceutical Journal","volume":"21 1","pages":"242 - 248"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47896053","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}
Alpesh Patel, Sayali Shah, Mukesh R. Patel, G. Vyas
Objective The present study was aimed at the development of a self-microemulsifying drug delivery system (SMEDDS) for the low water-soluble drug using quality by design (QbD) to enhance the bioavailability of drugs. Experimental work The components of the SMEDDS were preliminarily screened using the pseudoternary phase diagram as a solubility study. The patient-centric, quality target product profile, and critical quality attributes were earmarked. Preformulation studies were performed along with an initial risk assessment that facilitated the selection of lipids (i.e. Sefsol 218), surfactants (i.e. Acrysol EL-135), and cosurfactants (i.e. PEG 400) as Critical Material Attributes for the formulation of SMEDDS. Extreme vertices mixture design, given its utility and the pertinence to the design issue in hand, was chosen for the study. The various responses selected for this design were drug release at 20 min (%), transmittance (%), emulsification time (s), and globule size (nm). Eleven distinct formulations were prepared and measured to check the model fit. The optimization and model validation were finished by directing experimental runs. Results and discussion Sefsol 218 (oil), Acrysol EL-135 (surfactant), and PEG 400 (cosurfactant) showed the highest solubility. The fourier transform infrared spectroscopy (FTIR) study suggested that there may be no significant difference in the characteristic’s peak at a wavenumber of the drug in the presence of excipients. The studies have shown that the application of extreme vertices mixture design and the development of formulation in QbD resulted in a powerful and viable technique for improving the bioavailability of the drug. This was confirmed by the characteristics’ studies of the optimized batch like in vitro drug release in 20 min (73.44%), drug content (99.3%), emulsification time (25 s), transmittance (99.5%), droplet size (16.64 nm), polydispersibility index 0.170, and zeta potential −9.74 mV. A great agreement was observed among the predicted and experimental values for the average globule size and percentage of the drug released in 20 min. Furthermore, the optimal SMEDDS formulation exhibited fundamentally higher, extreme-plasma concentration, and area under the curve values a twofold higher value (P<0.05) than the teriflunomide suspension. Conclusion In summary, the present studies report successful QbD-oriented development of a novel oral teriflunomide-loaded SMEDDS formulation to noticeably improve the bioavailability of low water-soluble drugs.
{"title":"Quality by design approach to the development of self-microemulsifying systems for oral delivery of teriflunomide: design, optimization, and in vitro and in vivo evaluation","authors":"Alpesh Patel, Sayali Shah, Mukesh R. Patel, G. Vyas","doi":"10.4103/epj.epj_84_21","DOIUrl":"https://doi.org/10.4103/epj.epj_84_21","url":null,"abstract":"Objective The present study was aimed at the development of a self-microemulsifying drug delivery system (SMEDDS) for the low water-soluble drug using quality by design (QbD) to enhance the bioavailability of drugs. Experimental work The components of the SMEDDS were preliminarily screened using the pseudoternary phase diagram as a solubility study. The patient-centric, quality target product profile, and critical quality attributes were earmarked. Preformulation studies were performed along with an initial risk assessment that facilitated the selection of lipids (i.e. Sefsol 218), surfactants (i.e. Acrysol EL-135), and cosurfactants (i.e. PEG 400) as Critical Material Attributes for the formulation of SMEDDS. Extreme vertices mixture design, given its utility and the pertinence to the design issue in hand, was chosen for the study. The various responses selected for this design were drug release at 20 min (%), transmittance (%), emulsification time (s), and globule size (nm). Eleven distinct formulations were prepared and measured to check the model fit. The optimization and model validation were finished by directing experimental runs. Results and discussion Sefsol 218 (oil), Acrysol EL-135 (surfactant), and PEG 400 (cosurfactant) showed the highest solubility. The fourier transform infrared spectroscopy (FTIR) study suggested that there may be no significant difference in the characteristic’s peak at a wavenumber of the drug in the presence of excipients. The studies have shown that the application of extreme vertices mixture design and the development of formulation in QbD resulted in a powerful and viable technique for improving the bioavailability of the drug. This was confirmed by the characteristics’ studies of the optimized batch like in vitro drug release in 20 min (73.44%), drug content (99.3%), emulsification time (25 s), transmittance (99.5%), droplet size (16.64 nm), polydispersibility index 0.170, and zeta potential −9.74 mV. A great agreement was observed among the predicted and experimental values for the average globule size and percentage of the drug released in 20 min. Furthermore, the optimal SMEDDS formulation exhibited fundamentally higher, extreme-plasma concentration, and area under the curve values a twofold higher value (P<0.05) than the teriflunomide suspension. Conclusion In summary, the present studies report successful QbD-oriented development of a novel oral teriflunomide-loaded SMEDDS formulation to noticeably improve the bioavailability of low water-soluble drugs.","PeriodicalId":11568,"journal":{"name":"Egyptian Pharmaceutical Journal","volume":"21 1","pages":"167 - 186"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48752139","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：