Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
436
451
10.35333/jrp.2020.187
826
Synthesis, <em>in silico</em> studies and cytotoxicity evaluation of novel 1,3,4-oxadiazole derivatives designed as potential mpges-1 inhibitors
Gizem ERENSOY
Kai DING
Chang-Guo ZHAN
Ammar ELMEZAYEN
Kemal YELEKÇİ
Merve DURACIK
Özlem BİNGÖL ÖZAKPINAR
İlkay KÜÇÜKGÜZEL
series of new 1,3,4-oxadizole derivatives containing thioether group, has been synthesized to investigate their mPGES-1 inhibitory activities. The synthesized compounds were also evaluated for their anticancer and COX-1/2 inhibitory activities. All compounds were checked for their purity using TLC and HPLC analyses. The melting points, elemental analysis, FT-IR, 1H-/13C-NMR and LR-MS data were utilized for structural characterization. The most potent derivative was 2-[5-{[2-methyl-5-(propan-2-yl)phenoxy]methyl}-1,3,4-oxadiazol-2-yl)sulphanyl]-1-(phenyl)ethan-1-one 3a, which showed inhibitory activity against mPGES-1 with an IC50 of 4.95 μM. Docking studies with mPGES-1 and COX-1/2 enzymes revealed their affinity and potential binding mechanism for the tested compounds.
https://jrespharm.com/abstract.php?id=826
1,3,4-OxadiazolesthioethersmPGES-1 inhibitionCOX-1/2 inhibitionanticancer activitymolecular dockingADME prediction.
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
452
463
10.35333/jrp.2020.193
809
Novel nitrogen-containing heterocyclic compounds in gpr109a as an anti-hyperlipidemic: homology modeling, docking, dynamic simulation studies
Prajakta B. KOTHAWADE
Kiran Bharat LOKHANDE
Kakumani Venkateswara SWAMY
Sohan S. CHITLANGE
Asha B.THOMAS
Niacin or nicotinic acid therapy leads to reduction of the level of Low-density Lipoprotein cholesterol (20-40%) with significant elevation of High-Density Lipopreoin cholesterol level (20-35%). From research, it was said that Nicotinic acid might exert its positive action by activating the G-protein-coupled receptor (GPCR) which is found on adipocytes. GPR109A (family of GPCR) receptor was important for nicotinic acid (niacin) for its anti-lipolytic effects. As GPR109A is a targeted receptor for the treatment of dyslipidemia, its structural analysis needs to be elucidated. But the Protein 3D structure of target was not available at Protein Data Bank (PDB), so we have generated its structure through homology modeling and validation was carried out. Screening of top lead molecules with the help of various computational approaches like molecular-docking and molecular dynamic (MD) simulations studies with different online tools were carried out. The docking results showed that the lead compound 2B [(R)-methyl 2-(2-(1H-indol-3-yl) acetamido)-3-(1H-indol-3-yl) propionate] revealed significant binding energy value (-30.54 kcal/mol) as that with the nicotinic acid which is a standard drug (-17.68 kcal/mol). In addition to that, Molecular-Dynamic (MD) simulations analysis proved that compound 2B has lesser variations throughout the simulation period as represented by the root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) graphs. Current in silico study describes the modeling of novel heterocyclic compounds as antihyperlipidemic drugs for the treatment of dyslipidemia. This study also describes a deeper idea about the structural information of the lead compound 2B and its entire molecular interactions against GPCR109A and provides a hypothetical guideline to utilize this compound as an antihyperlipidemic for the treatment of dyslipidemia.
https://jrespharm.com/abstract.php?id=809
G-protein coupled receptor (GPCR)homology modelingantihyperlipidemic drugsnicotinic acidmolecular docking and molecular dynamic simulations
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
464
471
10.35333/jrp.2020.194
816
Acetylcholinesterase inhibitory potencies of new pyrazoline derivatives
Mehtap TUĞRAK
Halise İnci GÜL
İlhami GÜLÇİN
Alzheimer's disease (AD) has no current cure and its mechanism is not fully known, but treatments for symptoms are available. Acetylcholinesterase (AChE) has been reported to be an applicable therapeutic target in patient with AD. Acetylcholinesterase inhibitors (AChEIs) are commonly used for it. For this purpose, novel series of pyrazoline based compounds [2-(3-(4-methoxyphenyl)-5-aryl-4,5-dihydro-1H-pyrazol-1-yl)benzo[d]thiazole, 1-9] were synthesized and AChE inhibitory potencies were reported here. The results indicated that compound 1 (Ki= 0.13±0.004 μM) possessed the highest AChE inhibitory effect in series, which is two times more potent than the reference compound Tacrin (Ki= 0.26±0.045 μM). So, pyrazoline derivative 1 can be considered as a lead inhibitor in designing new AChE inhibitors.
https://jrespharm.com/abstract.php?id=816
Acetylcholinesterasealzheimer diseasebenzothiazolpyrazoline
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
472
478
10.35333/jrp.2020.195
820
Evaluation of cholinesterase inhibitory activity of six indonesian cassia species
Suciati SUCIATI
Erlinda Rhohmatul LAILI
Debora POERWANTORO
Anita Probo HAPSARI
Lailatul Zakiyah GIFANDA
Karma RABGAY
Wiwied EKASARI
Kornkanok INGKANINAN
Alzheimer’s disease (AD) is a neurodegenerative disorder, which is the most common cause of dementia. The aging population means that the number of people suffering from AD is expected to increase each year if there is no effective treatment found. One of the strategies for the treatment of AD is the use of cholinesterase inhibitors. Plants have been the source of many bioactive metabolites, including cholinesterase inhibitors. The objective of this study is to investigate the potency of several plant extracts from the genus Cassia as cholinesterase inhibitors. The cholinesterase inhibitory screening was carried out against two enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), according to the modified Ellman’s method. The chemistry of the active fractions was studied by LC-MS/MS method. The results suggested that amongst six plant extracts from the genus Cassia investigated, the ethanolic extract of Cassia spectabilis showed the strongest inhibition against both AChE and BChE enzymes, with IC50 values of 39.5 and 36.9 μg/mL, respectively. Investigation on the n-hexane, ethyl acetate, and n-butanol fractions obtained from the C. spectabilis extract showed that the ethyl acetate and the n-butanol fractions gave better inhibitory activity compared to the n-hexane fraction. Based on the LC-MS/MS data, the two active fractions gave similar profile. Both fractions contained alkaloid cassine and spectaline, which may responsible for the cholinesterase inhibitory activity.
https://jrespharm.com/abstract.php?id=820
Cholinesterase inhibitorAlzheimer’s diseaseCassia speciesCassia spectabilis
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
479
486
10.35333/jrp.2020.196
822
In vitro antihepatocellular carcinoma activity of secondary metabolites of centaurea kilaea boiss
Turgut ŞEKERLER
Ali ŞEN
Leyla BİTİŞ
Azize ŞENER
The aim of this study was to investigate in vitro cytotoxic effects of previously isolated compounds (taraxasterol, salvigenin, 3'-O-methyleupatorin, oleanolic acid, jaceosidin and pectolinarigenin) from Centaurea kilaea chloroform extract on hepatocellular carcinoma cell lines, HepG2 and Hep3B, as well as to evaluate the effect on the normal cell line, NIH3T3. In vitro antihepatocellular carcinoma activity of compounds was assessed by MTT method. All compounds except pectolinarigenin caused more inhibition on HepG2 rather than Hep3B. Among these compounds, it was found that Jaseosidin had the highest anticancer activity with IC50 values of 137.66 μg/mL and 147.66 μg/mL on the HepG2 and Hep3B cell lines, respectively. 3'-O- methyleupatorin showed the second highest cytotoxicity with IC50 values of 151.98 μg/mL and 159.24 μg/mL against the HepG2 and Hep3B cell lines, respectively. The results indicated that Jaseosidin and 3'-O- methyleupatorin, had the best antiproliferative activity against hepatocellular carcinoma cell lines. Also, according to our best knowledge, this study is first report on antihepatocellular carcinoma activity of Jaseosidin and 3'-O- methyleupatorin.
https://jrespharm.com/abstract.php?id=822
Centaurea kilaeaanticancer activityhepatocellular carcinomajaceosidin3'-O-methyleupatorin
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
487
496
10.35333/jrp.2020.197
825
Quantification of phenolic and flavonoid contents and some biological activities of ornithogalum sigmoideum freyn & sint
Can Özgür YALÇIN
Sezen YILMAZ SARIALTIN
Derya ÇİÇEK POLAT
Ornithogalum L. is a genus containing approximately 200 species that grow in warm areas of Europe, Asia and Africa. 54 of these species grow naturally in Turkey. They have been used for various medicinal purposes such as emetic and against abscess since ancient times and today consumed as food especially in the eastern region of the Black Sea. Ornithogalum species were found to be rich in cholestane glycosides, cholestane bidesmosides, cardenolide glycosides, flavonoid glycosides and saponins. According to the health-promoting effects of these compounds; we aimed to study, antioxidant, anti-inflammatory and cytotoxic effects of aerial parts and bulbs of Ornithogalum sigmoideum as well as bioactive compounds. The antioxidant activity was determined using 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Anti-inflammatory activity of extracts was evaluated by the human red blood cell membrane stabilization method. Total phenolic and flavonoid contents were evaluated by Folin–Ciocalteu and aluminum chloride methods, respectively. The cytotoxic effects were evaluated on lung (A549), colorectal (HCT-116) and prostate (PC3) cancer cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Methanolic extract of aerial part of O. sigmoideum exhibited the greatest anti-inflammatory and antioxidant activity in all methods determined. Supporting these results, the highest amounts of total phenolic and flavonoid were obtained from this extract. MTT cell viability results showed that aerial part extract of O. sigmoideum was induced cell death more than the bulb extract in every-three cell line and the PC3 cells were more sensitive than the others were. However, the calculated IC50 values of all the extracts were too high for considering as cytotoxic.
https://jrespharm.com/abstract.php?id=825
Antioxidantanti-inflammatorycytotoxicityfree radicalOrnithogalum sigmoideum
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
497
507
10.35333/jrp.2020.198
824
Evaluation of phenolic compounds and protective effects of olive (olea europaea l.) leaf extracts on endothelial cells against hydrogen peroxide-induced toxicity
Hilal TORUL
Nurgün KÜÇÜKBOYACI
Uğur TAMER
Çimen KARASU
Olea europaea L. (Oleaceae) leaves have been used for centuries in folk medicine to treat many degenerative and inflammatory diseases including hypertension, atherosclerosis and cardiovascular disorders. The present study was aimed to quantify the phenolic compounds present in three different extracts of O. europaea leaves, and to demonstrate their protective effects on human umbilical vein endothelial cells against oxidative injury induced by H2O2. Oleuropein, hydroxytyrosol, quercetin, luteolin and rutin in the olive leaf extracts were quantified by using a validated HPLC-UV method. Total phenolic content was determined using the Folin-Ciocalteau assay. The MTT and dichlorofluorescein assays were conducted to measure cytotoxicity and intracellular reactive oxygen species generation, respectively. Oleuropein was the major phenolic component. Each phenolic compound (1.0 and 10.0 μM) and each extract (10.0 μg/mL) significantly (p<0.05) preserved human umbilical vein endothelial cells against H2O2-induced toxicity, but olive leaf extract-1 and luteolin seemed to be more effective in studied concentrations even in the inhibition of cellular reactive oxygen species generation (p<0.05). In addition, a positive correlation was found between reactive oxygen species inhibitory activity and total phenol content versus viability protecting capacity of each olive leaf extracts. These results supply a new validated HPLC method for the effective characterization of olive leaf polyphenolic compounds and support the notion that the polyphenolic components of olive leaves are the efficient cytoprotective agents against H2O2-induced oxidative stress and toxicity in human umbilical vein endothelial cells.
https://jrespharm.com/abstract.php?id=824
Olea europaeacytoprotectionHPLColeuropeinhydroxytyrosolquercetinluteolinrutin
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
508
517
10.35333/jrp.2020.199
819
Protective effect of caesalpinia sappan l. extract against h<sub>2</sub>o<sub>2</sub>-induced oxidative stress on hacat and its formulation as antioxidant cream
Leonny Yulita HARTIADI
Agnes Anania Triavika SAHAMASTUTI
Oxidative stress arises from excessive generation of reactive oxygen species and it is known to be the major factor that accelerates skin aging and involved in the development of skin inflammatory disorders. Therefore, there is a need to develop cosmetics products containing active ingredient with potent antioxidant effect. One of medicinal plants that is potential to be utilized as an active ingredient for cosmetics is Caesalpinia sappan L. Previous studies demonstrated the potent antioxidant activity of C. sappan in numerous in vitro scavenging free radicals assay. The present study aims to evaluate the antioxidant of C. sappan in a biological system and further formulates the extract in cream formulation. Powdered C. sappan was macerated with 96% ethanol and the dried extract was assessed for the cytotoxic and antioxidant effect on human keratinocytes cell line using MTS assay. Several cream formulations containing non-toxic concentration of C. sappan extract were made and evaluated. Cytotoxicity assay showed that C. sappan extract had an IC50 of 146.8±2.6 μg/ml. At a concentration of 15.625 μg/ml, the extract exhibited a protective effect against oxidative stress induced by H2O2 that was comparable to vitamin E. All of the formulated creams were o/w cream type, homogenous and had white-pinkish color. pH were in a range of 5.07±0.01 – 6.51±0.04 with shear-thinning properties. Following freeze-thaw cycle, the formulas were found to be stable and no significant changes were observed, except for viscosity. This study demonstrates that several cream formulations of C. sappan extract have been successfully formulated with proven antioxidant property.
https://jrespharm.com/abstract.php?id=819
Caesalpinia sappan L.antioxidantcreamcytotoxicityhuman keratinocytes cell line
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
518
528
10.35333/jrp.2020.200
823
Thin layer chromatography as a simple and quick in-process tool for qualitative and semi-quantitative determination of unentrapped drugs in liposomal formulations
Mukesh KUMAR
Swaroop Rameshwarji LAHOTI
Control of free or unentrapped drug is one of the key quality attributes for liposomal drug delivery systems. Conventional methodologies for estimating unentrapped drug in liposomal formulations require prior separation, which are time-consuming and complex. There is a need for a quick in-process analytical technique, which can enable monitoring of drug loading during various stages of product development and manufacturing. A novel simple and rapid TLC procedure was developed for evaluating entrapment efficiency in liposomal formulations. The method is based on differential radial migration of free and entrapped drug on silica gel TLC plates. The method can be employed either as a simple visual qualitative tool in the early screening studies or in a semi-quantitative mode for detection of free and unentrapped drugs. In case of doxorubicin hydrochloride, a deep-red coloured molecule, the method enabled free drug detection up to the levels as low as 2.5%. This method precluded the need of developing the plate further with the mobile phase. The method was used successfully in product development or as an in-process monitoring tool. The method’s potential for characterizing entrapment efficiency was evaluated for less intensely coloured or UV absorbing drug candidates such as amphotericin B liposome and curcumin liposome. The preliminary results post derivatization with ninhydrin reagent or visualization under UV light indicated applicability of technique in general for liposomal delivery systems of various other drugs. According to the best of the author’s knowledge, there has been no reports on the evaluation of drug entrapment using such TLC based technique so far.
https://jrespharm.com/abstract.php?id=823
Liposomal formulationUnentrapped or free drugThin layer chromatographySupramolecular characterization
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
529
538
10.35333/jrp.2020.201
821
Formulation and optimization of gellan gum-poloxamer based dexamethasone mucoadhesive in situ gel
Seda RENÇBER
Sinem Yaprak KARAVANA
The main objective of the present study was to formulate and evaluate mucoadhesive in situ buccal gels of dexamethasone based on gellan gum-poloxamer 407. Formulations were characterized for gelling capacity, drug content, pH, viscosity, rheological studies, mechanical studies and in vitro drug release. The drug content, clarity and pH of the formulations were found to be satisfactory. Mucoadhesive in situ gels showed thermoresponsive behavior, existing as a liquid at room temperature and gel at 30–37ºC. Formulations exhibited pseudoplastic flow and typical gel-type mechanical spectra (G′ > G″) at different frequecy values and 37ºC. Prepared gels resulted in preparations with desirable rheological features as well as texture (appropriate hardness, compressibility, adhesiveness, cohesiveness and elasticity) properties, which could benefit the therapeutic efficacy, by increasing the residence time and easiness for local application on the buccal mucosa. Additionally, the developed preparations exhibited sustained drug release up to 72 h as intended for these systems. Optimized formulation containing 14% w/v poloxamer 407 and 0.4% w/v gellan gum exhibited desired characteristics (mechanical and rheological properties) for developing buccal drug delivery systems. Thus, buccal dexamethasone loaded mucoadhesive in situ gel was found to be a promising formulation.
https://jrespharm.com/abstract.php?id=821
Dexamethasonegellan gumpoloxamerin situ gelbuccal drug delivery
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
539
551
10.35333/jrp.2020.202
817
Formulation and pharmacokinetic evaluation of rifampicin solid lipid nanoparticles
Ahmed GARDOUH
Alshimaa GAMAL
Shadeed GAD
This study aims to optimize RIF loaded solid lipid nanoparticles (RIF-SLNs) to sustain its release and enhance its oral absorption and bioavailability. RIF loaded SLNs were formulated by a modified micro emulsion-based technique using two different lipids (Cetyl palmitate and Glyceryl monostearate) and two different surfactants (Tween®80 and Poloxamer 188). Particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (E.E), drug loading capacity (L.C), in vitro drug release, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) were determined for RIF loaded SLNs formulae. Pharmacokinetic study was performed on optimized RIF-SLNs, marketed RIF and pure drug suspension in Wistar rats. The particle size, PDI, E.E% and L.C% of optimized formula were recorded as 0.183 μm, 0.420, -34.7 mV, 80.8% and 0.216%, respectively. In vitro release studies suggested that all SLNs formulae possessed a burst release created from the unloaded drug and adsorbed drug molecules at SLNs surface then sustained release due to diffusion of drug from lipid matrix over a period of 120 h. From the release kinetics data, the release rate of RIF from all formulae fitted into Higuchi’s diffusion model. Pharmacokinetic study showed significant enhancement in RIF-SLNs relative bioavailability 5.86 and 2.33 folds in comparison with pure RIF suspension and marketed RIF. RIF loaded SLNs were formulated successfully by a modified micro emulsion-based method. Also, oral drug delivery can be enhanced by SLNs which showed improvement in the oral bioavailability of the drug.
https://jrespharm.com/abstract.php?id=817
Pharmacokinetic enhancementrifampicinIn vitro releasesolid lipid nanoparticlesglyceryl monostearatecetyl palmitate
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
552
561
10.35333/jrp.2020.203
818
Dolutegravir sodium loaded solid lipid nanoparticles: a vaginal drug delivery system for pre-exposure prophylaxis of hiv
Ruhi ANJUM
PK LAKSHMI
The objective of this study was to formulate dolutegravir sodium an antiretroviral drug into topical (vaginal) semisolid solid lipid nanoparticle gel formulation using a rapid, economical one step process. Solid lipid nanoparticles formulations were prepared using solvent injection method combined with sonication, using different type of lipids (e.g. Phospholipon 80H, Phospholipon 90H and Soy lecithin) and surfactants (Poloxamer 407, Poloxamer 188, and Tween 80). The SLN gel was formed in one step process using poloxamer 407 & water forming aqueous phase and stearic acid & phospholipon 80H in ethanol forming lipid phase. The lipid phase was injected into aqueous phase forming a creamy gel at 70⁰ C. Hence it does not require any gelling agent. It was optimized using a systematic approach of design of experiments. The formulation was evaluated for particle size, polydispersity index, zeta potential, flux, entrapment efficiency and results were found to be 455 nm, 0.411, -26.6 mV, 43.7±-0.12 μg/cm2/hr, 76.2% respectively. Drug release studies were conducted using two membranes via; dialysis membrane and goat vaginal tissue. The release pattern of the drug followed first order kinetics with Higuchi release mechanism. The release exponent ‘n’ of the Korsemeyer equation indicates the Fickian diffusional drug release. The ex vivo vaginal study of F2 formulation showed 64.89% of tissue deposition, which was 16 times more than the pure drug. This study concluded that the dolutegravir sodium, a sustained release solid lipid nanoparticle gel may have increased vaginal deposition and might show site targeted effect.
https://jrespharm.com/abstract.php?id=818
Dolutegravir sodiumsolid lipid nanoparticlessolvent injection methodvaginal deliverygel
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
562
571
10.35333/jrp.2020.204
802
Formulation and evaluation of fluvastatin sodium drug-in-adhesive transdermal system
Rachel GEEVARGHESE
Satish SHIROLKAR
Current investigation is aimed at designing a fluvastatin sodium loaded drug-in-adhesive patch (DIA Patch ) to overcome the problems associated with the daily oral administration of the drug. The patches were prepared by solvent casting method using acrylate emulsion polymers like covinax 525-78, mowinyl 461 and novacryl PSR32 which served as sustained release matrix polymer and adhesive. Methocel K-15M was added as a solubilizer whereas transcutol, oleic acid and isopropyl myristate were tried as permeation enhancers for the drug-in-adhesive patch. The combination of mowinyl-isopropyl myristate patch was further optimized by 32 factorial design to study the effect of two independent variables i.e. concentration of solubilizer and permeation enhancer on responses i.e.% drug release, tensile strength and peel adhesion strength. The formulation was further evaluated for its lipid lowering activity and skin irritation index. The % cumulative release of drug at the end of 24 h was found to be 87.74%. The formulation shows tensile strength of 12.75 kg/cm2 and peel adhesion strength of 32.44 N/25 mm. The Primary irritation index (PII) for DIA patch was found to be 0.22. The fluvastatin sodium loaded DIA patch significantly inhibits serum cholesterol and triglyceride levels as compared to oral control (p<0.01) in triton WR 1339 induced hyperlipidemic rat. Hence the developed transdermal patch could be acceptable for transdermal use.
https://jrespharm.com/abstract.php?id=802
Pressure-sensitive–adhesivefluvastatin sodiumdrug-in-adhesive patch% cumulative releasepeel adhesion strengthtotal cholesterol
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
572
581
10.35333/jrp.2020.205
815
Development of a multiple-unit system: tablets containing amlodipine besylate which have different release kinetics
Ozan TEKDEMİR
Gizem TİLKİ
Timuçin UĞURLU
Multiple-unit systems may include tablets, capsules, pellets in a single administration. Once-a-day administration of Amlodipine Besylate (AML) accounts for fluctuation of plasma drug concentrations between dosing intervals. The aim of this study is to develop an extended-release (ER) and an immediate-release (IR) tablet to overcome the fluctuation of plasma drug concentrations. To achieve this purpose, 9 IR tablets and 6 ER tablet formulations were developed. The dissolution media for IR tablets was pH 2 for 1 hour and the dissolution media for ER tablets was pH 2 for 2 hours, and afterwards was pH 6.8 for 10 hours. The amount of AML released into the dissolution media was measured by Mettler Toledo UV 5 at a wavelength of 238 nm. The dissolution data of IR and ER tablets were statically evaluated. The highest dissolution rate for IR tablets (93%) was achieved with the IR-5 formulation. For ER tablets, a 50% drug release was achieved with the ER-1 and ER-4 formulation. The drug release kinetics of all ER tablets were calculated and subsequently the ER-1 formulation, which has Higuchi drug release kinetics, was chosen as the ER tablet. Lastly, a dissolution study of the selected formulations (IR-5 and ER-1) was conducted in the same vessel. After 12 hours of the dissolution study, drug release was found to be 79% ±0,92 (close to 75% which was targeted). Multiple-unit systems that have different tablet formulations in one administration could be used to enhance drug release kinetics that cannot be achieved with conventional tablets.
https://jrespharm.com/abstract.php?id=815
Multiple unit systemamlodipine besylateimmediate release tabletextended release tabletfluctuation of plasma drug concentrationhydroxyl propyl cellulosesodium starch glycolatecrospovidon
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
582
592
10.35333/jrp.2020.206
813
Evaluation of regular uplc/ms system for experimental and clinical proteomics
Engin KOÇAK
Sacide ALTINÖZ
The objective of this study was to investigate if UPLC/MS system without chip or Jetstream technology could be used in proteomics. A regular UPLC column (2.1 mm × 150 mm, 1.7 μm) was used to separate peptides at a flow rate of 0.200 mL/min. First, bovine serum albumin samples were analyzed with intra- and inter-day (11 days) experiments. In Escherichia coli experiments, 518 proteins were identified and subsequently investigated with PANTHER gene list and KEGG pathway. Results demonstrated that UPLC/MS provides detailed information regarding cellular process. Finally, we analyzed human plasma sample to observe if UPLC/MS system could be used to analyze body fluids. We identified 87 proteins in the plasma sample, and the identified proteins were investigated in terms of molecular biology. The results showed that UPLC/MS system could provide promising results for experimental and clinical proteomics.
https://jrespharm.com/abstract.php?id=813
ChromatographymaxquantproteomicsE. coliplasma
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2020
24
4
593
601
10.35333/jrp.2020.207
814
Metabolic response of escherichia coli to subinhibitory concentration of ofloxacin
Engin KOÇAK
Ceren ÖZKUL
Antibiotic resistance is one of the most important problems worldwide. In order to overcome antibiotic resistance, pathogen-antibiotic interactions should be investigated at molecular level. In our present study, we focused on metabolic differences in Escherichia coli (E. coli) under ofloxacin stress to understand adaptation and resistance mechanisms. We used GC/MS based metabolomics approach for metabolite identification and quantification. Experimental results showed that 17 metabolites were altered under subinhibitory concentration of ofloxacin. Pathway analysis indicated that TCA cycle, glyoxylate and dicarboxylate metabolism, biosynthesis of fatty acids, glutathione metabolism were induced by ofloxacin. Moreover, we evaluated metabolites individually and we found that spermine and L-ascorbic acid increased in ofloxacin treated groups. These metabolites are important in resistance and detoxifying processes in cells. In conclusion, altered metabolome profile gave information on adaptation and resistance processes in E. coli against ofloxacin. These metabolic changes will help to enlighten resistance mechanisms and discover novel treatment strategies against the pathogens.
https://jrespharm.com/abstract.php?id=814
Metabolomicsantibiotic resistanceGC/MSMS-DIALTCA cycle