Interchangeability and Comparative Effectiveness between Micronized and Non-micronized Products of Glibenclamide Tablets

Background: During the last few years there was wide debate about the interchangeability and effectiveness between circulated products containing Glibenclamide in the market.Objectives: This study aimed to compare the effectiveness of this product “non-micronized” to the originator’s product of Glibenclamide tablets “of micronized” sulfonylurea.Methods: 12 volunteers received a dose of 5mg of Glibenclamide (from test and standard products) under fasting conditions in two separate sessions using randomized crossover design. Blood glucose level for the volunteers was monitored to avoid the development of hypoglycemia. Plasma samples were collected over 24 hours and analyzed using HPLC.Results: The maximum concentration Cmax for the test and reference products were 2.508 ± 0.104 and 3.526 ± 0.118 (ìg/ml) respectively and the area under the curve AUC0-[ were 3.511 ± 0.153 4.572 ± 0.202 (ìg.h/ml) for these products respectively, with a difference of about 24% between the test and reference products in its AUC.Conclusions: The results indicate that the test product is not bioequivalent to reference product. The difference in formulation between micronized product and non-micronized product of Glibenclamide tablets has impact on clinical outcomes.Key words:sulfonylurea,Blood glucose,hypoglycemia

IN VITRO-IN VIVO BIO-EQUIVALENCE CORRELATION STUDY OF METRONIDAZOLE, AND ITS BRANDS OF IMMEDIATE RELEASE TABLET UNDER BIO-WAIVER CONDITIONS

Objective: The aim of present study is to examine the in-vitro in-vivo correlation (IVIVC) of immediate release product. Metronidazole 500mg and its brands of immediate release dosage forms. Metronidazole is clearly classified into BCS class I, and could be evaluated under bio waiver conditions. Methods: The in vitro parameters employed were hardness, weight uniformity, friability, disintegration time, absolute drug content, dissolution rate (in 0.1 N Hydrochloric acid, phosphate buffer and acetate buffer at 37ºC), and dissolution efficiencies were also analyzed. The in-vitro dissolution study was performed on the brands, according to FDA,USP dissolution profile in three different PH (1.2), (4.5), and (6.8) at37ºC, using the USP apparatus II, then f1, f2 were determined for the time intervals of 10, 15, 30, 45 and 60 minutes, and dissolution efficiencies were calculated. MINITAB 14 statistical program used for in vitro in vivo correlation, level A was done for reference product. Results: A non linear relation was established which is typical for immediate release formulation, of class 1. There was significant relationship between in vitro and in vivo data of reference metronidazole product, Correlation and distribution of data with correlation coefficient (r=0.724, 0.837, 0.707), nonlinear relationship with p-value (>0.05) =(0.167, 0.098, 0.182), there is no out lines, no lake of fits at P-Values=0.0040, 006, 0.026.Conclusion: Study concluded that there is no linear correlation between percent of drug released and percent of drug absorbed ,this may be due to uncontrollable gastric emptying rate for class one Metronidazole.                          Peer Review History: Received 2 January 2020;   Revised 1 February; Accepted 3 March, Available online 15 March 2020 Academic Editor: Ahmad Najib, Universitas Muslim Indonesia,  Indonesia, [email protected] Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 4.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Hayriye Eda Şatana Kara, Gazi University, Turkey, [email protected] Dr. Mohamed Ismail Nounou, Appalachian College of Pharmacy, Oakwood, Virginia, USA, [email protected] Similar Articles: IN VITRO-IN VIVO BIO-EQUIVALENCE CORRELATION STUDY OF ATENOLOL, AND ITS BRANDS OF IMMEDIATE RELEASE TABLET UNDER BIO-WAIVER CONDITION

IN VITRO-IN VIVO BIO-EQUIVALENCE CORRELATION STUDY OF ATENOLOL, AND ITS BRANDS OF IMMEDIATE RELEASE TABLET UNDER BIO-WAIVER CONDITIONS

Objective: The aim of present study is to examine the in vitro-in vivo correlation (IVIVC) of immediate release product. Atenolol 100mg and its brands of immediate release dosage forms. Atenolol is clearly classified into BCS class III, and could be evaluated under bio waiver conditions. Methods: The in vitro parameters employed were hardness, weight uniformity, friability, disintegration time, absolute drug content, dissolution rate (in 0.1 N Hydrochloric acid, phosphate buffer and acetate buffer at 37ºC), and dissolution efficiencies were also analyzed. The in-vitro dissolution study was performed on the brands, according to FDA, USP  dissolution profile in three different PH (1.2), (4.5), and (6.8) at 37ºC, using the USP apparatus II. A non linear relation was established which is typical for immediate release formulation, of class III. Results: All Atenolol brands released about 90% drug in PH (6.8), where about 87% in PH (4.5), reference drug released about 91% and test drug released about 87% in pH (1.2). Dissolution efficiency of  the entire brands differed by less than 10% from the innovator brand. According to MINITAM 14 statistical program, there was significant relationship between in vitro and in vivo data of reference Atenolol product. Conclusion: By applying level A in vitro-in vivo correlation, study concluded that there is no linear correlation between percent of drug released and percent of drug absorbed, this may be due to uncontrollable permeability rate for class three Atenolol.                    Peer Review History: Received 20 September 2019;   Revised 16 December; Accepted 7 January, Available online 15 January 2020 Academic Editor: Dr. Amany Mohamed Alboghdadly, Princess Nourah bint abdulrahman university, Riyadh, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 3.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Hayriye Eda Şatana Kara, Gazi University, Turkey, [email protected] Dr. Nicola Micale, University of Messina, Italy, [email protected] Similar Articles: FAST DISSOLVING DRUG DELIVERY SYSTEMS: FORMULATION, PREPARATION TECHNIQUES AND EVALUATION FAST DISSOLVING TABLETS: A PROMISING APPROACH FOR DRUG DELIVERY DEVELOPMENT AND EVALUATION OF FAST DISSOLVING THIN FILMS OF ARIPIPRAZOLE TABLET GRANULATION: CURRENT SCENARIO AND RECENT ADVANCE

Evaluation of Punica granatum Peel Against Diabetic Wound Infection

Background: Foot infections are a common and serious problem in diabetic patients.Objectives: To investigate the antibacterial activity of some medicinal plants used by traditional healers for diabetic wounds and to examine in-vivo wound healing activity of active extracts.Materials and Methods: An experimental study in which fifteen plant extracts subjected to preliminary antibacterial screening against six standard organisms (Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa and Staphylococcus aureus) using cup-plate agar diffusion method and the result was compared with activity of commonly used antibiotics. The minimum inhibitory concentration (MIC) was determined for active extracts using agar plate dilution method. The two extracts was screened against 180 clinical isolates obtained from diabetic wound infection. In this study the wound healing effect of methanolic extracts of Punicagranatum peels was tested on open skin wound model on Swiss Wistar Albino rats.Results: Fourteen extracts (93.3%) exhibited inhibitory activity against one or more of the six organisms. The MICs of the methanolic and aqueous extracts of Punica granatum were very low against all organisms. 180 clinical isolates were obtained from diabetic wound infection, the results of identification showed that 30 were Escherichia coli, 15 Klebsiella pneumoniae, 45 Proteus spp, 15 Pseudomonas aeruginosa, 60 Staphylococcus aureus and 15 Staphylococcus epidermidis. The methanolic extract of Punica granatum peels had inhibitory effect against 99.4% of the isolates at concentration 100mg/ml. The aqueous extract has inhibitory effect against 91.7% of the isolates. Results were obtained by measuring the wound healing percentage. In the first group, healing was completed in 15 days. In the second group and third group, 13 days were required for the completion of healing.Conclusion: The results of this study indicated that the methanolic extract of Punica granatum had high antibacterial activity and have wound healing activity.Key words: Antimicrobial activity, wound healing, Punica granatum

Preliminary phytochemical evaluation and seed proximate analysis of Surib (Sesbanialeptocarpa DC.)

Background: Surib (Sessbanialeptocarpa) of the family Leguminosae is a wild plant widely spread in Gezira scheme and sometimes its seeds unavoidably get mixed with machinery-harvested crops especially wheat. Different parts of Surib have been used traditionally for various illnesses in Africa where the plant spread widely.Objectives: To evaluate the nutritional value of Surib.Methods: The preliminary phytochemical screening was performed using the conventional chemical tests using precipitation and color reagents as appropriate, while the standard methods of the Association of Official Analytical Chemists, 1980 were used for the determination of the proximate seed composition.Results: Preliminary phytochemical screening of different plant parts (seeds, leaves and roots) extracts showed the presence of alkaloids in seeds and roots. Seeds and leaves of the plants were found to contain saponins, flavanoids, anthraquinones and tannins while the roots are devoid of these constituents. Proximate analysis of the seed revealed that carbohydrates and crude fibers constitute about 80% while proteins and fats values were 5.25 and 6.13% respectively.Conclusion: The nutrient value of Surib seed is negligible for its low content of proteins and fatty substances and thus it is of no use as animal or human food. The qualitatively determined antinutrient phytoconstituents as tannins, alkaloids, saponins and flavanoids in the seed could be considered as another main limitation to effective utilization of Surib as an animal feed and/or human food.Keywords: Sesbania leptocarpa, proximate analysis, phytochemical screening

Production of salinity tolerant Nile tilapia, Oreochromis niloticus through traditional and modern breeding methods: II. Application of genetically modified breeding by introducing foreign DNA into fish gonads

This study was conducted to produce a salinity tolerant Nile tilapia, Oreochromis niloticus through genetically modified breeding by introducing a fragmented purified DNA isolated from sea bream, Sparus aurata or Artemia, Artemia salina into the gonads. The results showed a significantimprovement (P . 0.05) in most of the growth performance and feed utilization parameters of genetically modified O. niloticus treated with sea bream-DNA and reared at different salinity levels up to 16 ppt compared to both genetically modified O. niloticus treated with Artemia-DNA and the control fish reared at the same salinity levels. Genetically modified O. niloticus treated with Artemia-DNA reared at 32 ppt, had displayed better traits results (P. 0.05) compared to the other fish within the same salinity level. Furthermore, genetically modified O. niloticus treated with sea bream-DNA showed a silver color covering all the body and no dark vertical bands. The results of the random amplified polymorphic DNA (RAPD) fingerprinting showed highly genetic polymorphic percentage (35.95%) among fish receiving foreign DNA and their control using different random primers. The results of the present work suggested that, hyper-saline genetically modified O. niloticus with higher growth rate can be producedusing a feasible and fast methodology.Key words: Salinity tolerance, Oreochromis niloticus, productive performance, genetically modified, DNA transfer

Phytochemical and Antibacterial Evaluation of Parinari curatetellifolia Planch Ex Benth (Chrysobalanaceae)

Parinari curatellifolia Planch ex Benth (Chrysobalanaceae) is used in traditional medicine for the treatment of pneumonia, wound infections, dressing of fractures and dislocation. P.curatellifolia stem bark extracts in methanol, ethylacetate and n-butanol were evaluated for antibacterial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis using cup plate method. The extracts were used at 50mg/ml concentration. The extracts were also screened for the presence of some secondary metabolites. The result of the antibacterial screening produced zones of inhibition ranging from 12-21mm for the methanolic extract while the ethylacetate and n-butanol fractions showed inhibition zones of 16-24mm respectively. The aqueous extract showed inhibition zones ranging from 12-20mm. Ampicillin (0.01mg/ml) used aspositive control, showed zones of inhibition ranging from 14-34mm. Ethylacetate fraction was the most active of the extracts on the test bacterial species. Water was used as negative control. The extracts inmost cases compared favorably with the ampicillin. The activity of the extracts was more on the gram positive bacteria than on the gram negative ones. The minimum inhibitory concentrations (MICs) of theethylacetate fraction for B. subtilis, P. aeruginosa were 1.56mg/ml each, for E.coli and S. aureus were 3.13 mg/ml and 0.78mg/ml respectively. The minimum bactericidal concentrations (MBCs) of the ethylacetate fraction for B.subtilis and S. aureus were 6.25mg/ml each, for P. aeruginosa and E.coliwere 12.50mg/ml each. The phytochemical screening revealed the  presence of anthraquinones, tannins, saponins, flavonoids,  cardiacglycosides, terpenoids, and carbohydrates. The antibacterial activity of the extracts may be attributable to the presence of these compounds in the extracts. The findings of this work lend support to the ethnomedical use of the plant.Key Words: Antibacterial; Phytochemistry; MIC; MBC; Parinari curatellifoli

Transcriptomic profiling of tumor-infiltrating CD4 + TIM-3 + T Cells reveals their suppressive, exhausted, and metastatic characteristics in colorectal cancer patients

T cell immunoglobulin mucin-3 (TIM-3) is an immune checkpoint identified as one of the key players in regulating T-cell responses. Studies have shown that TIM-3 is upregulated in the tumor microenvironment (TME). However, the precise role of TIM-3 in colorectal cancer (CRC) TME is yet to be elucidated. We performed phenotypic and molecular characterization of TIM-3+ T cells in the TME and circulation of CRC patients by analyzing tumor tissues (TT, TILs), normal tissues (NT, NILs), and peripheral blood mononuclear cells (PBMC). TIM-3 was upregulated on both CD4+ and CD3+CD4− (CD8+) TILs. CD4+TIM-3+ TILs expressed higher levels of T regulatory cell (Tregs)-signature genes, including FoxP3 and Helios, compared with their TIM-3− counterparts. Transcriptomic and ingenuity pathway analyses showed that TIM-3 potentially activates inflammatory and tumor metastatic pathways. Moreover, NF-κB-mediated transcription factors were upregulated in CD4+TIM-3+ TILs, which could favor proliferation/invasion and induce inflammatory and T-cell exhaustion pathways. In addition, we found that CD4+TIM-3+ TILs potentially support tumor invasion and metastasis, compared with conventional CD4+CD25+ Tregs in the CRC TME. However, functional studies are warranted to support these findings. In conclusion, this study discloses some of the functional pathways of TIM-3+ TILs, which could improve their targeting in more specific therapeutic approaches in CRC patients

The role of hepatic progenitor cells in predicting response to therapy in Egyptian patients with chronic hepatitis C, genotype 4

Background: Interferon therapy is used as a line of treatment of chronic hepatitis C virus (HCV) in several areas of the world including Egypt.Objective: Our aim was to investigate the value of hepatic progenitor cells (HPCs) in predicting response of patients with chronic HCV, genotype 4 to pegylated interferon (PEGIFN) plus ribavirin (RBV) therapy.Methods: Pre-treatment liver biopsies obtained from 110 patients with chronic HCV, genotype 4 were examined immunohisto- chemically for HPCs using cytokeratin19. The mean number of HPCs as ductular reaction (DR) and as isolated progenitor cells (IPCs) was counted in each case. The patients were classified into: those with sustained virological response (SVR) and those who did not achieve SVR. The results were compared between the two groups. Also, the relationships between HPCs and other clinico-pathologic variables were estimated using multivariate analysis.Results: The mean number of HPCs was the only independent predictor of therapeutic response, being significantly higher in non-responders (P = 0 for DR and P = 0.03 for IPCs). On the other hand, fibrosis stage and steatosis were the only independent factors which showed a significant direct association with the mean number of HPCs in the form of DR and IPCs (P = 0 for each).Conclusion: The number of HPCs provides prognostic information in chronic HCV since it is significantly associated with stage of fibrosis. More importantly, it can be used as a marker to predict response of patients with chronic HCV to PEGIFN plus RBV therapy.Keywords: Chronic hepatitis C, genotype 4, response to therapy, hepatic progenitor cells

Participatory mapping for transformation: multiple visual representation of foodscapes and environment in informal settlements in Nairobi

Although branded as ‘obstructionists’ and major agents of ‘disease and filth’ by city authorities, food vendors remain the pivotal node in the local food system in most informal settlements; therefore, their interaction with the environment and infrastructure services, and challenges they face to keep the food safe to eat, requires further grounded exploration. Food vendors from informal settlements in Nairobi, Kenya, who are acting as mappers and change agents, are building multi-layered views of places through the deliberative process of knowledge coproduction by participatory sensing, which lead to opportunities and challenges to improve those places