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  • Item type: Item ,
    Phytochemical and bioactivity study of Eryngium billardieri F. delachlore and Eryngium thyrsoideum Boiss
    (Tabriz University of Medical Sciences, School of Pharmacy, 2025) Sardari, Keyvan; Delazar, Abbas; Asgharian, Parina
    Introduction: Eryngium species have long been used in ethnomedicine for various purposes, such as stomach disorders, lowering blood sugar, antidote and wound healing.Scope: The aim of this study was to investigate some phytochemical and biological features of two species, Eryngium billardieri and Eryngium thyrsoideum.Methods and materials: The aerial part of E. billardieri and the aerial part of E. thyrsoideum were extracted using various solvents with increasing polarity. C18 sep-pak was applied for fractionation of methanol extracts. Further purification of fractions done through HPLC and preparative TLC techniques. Structure elucidation of isolated compounds was accomplished by 1HNMR and 13CNMR and two dimentional NMR methods. Essential oil and fatty acid contents were analyzed via GC-MS method. Total phenol and flavonoid contents were assayed. Antioxidant, antimalarial, α-glucosidase inhibitory and cytotoxic properties were evaluated in all samples. Results: Isolation of compounds in methanol extracts resulted elucidation of seven compounds. Four compounds in methanolic extract of E. thyrsoideum aerial parts, including: 3ʹ-glucopyranosyl rosmarinic acid, Bergaptene, Rutin and Quercetine. Three compounds in methanolic extract of E. billardieri aerial part, including 4ʹ-glucopyranoyloxy-hydroxyphenyl caffeate, chlorogenic acid and decursine. The results indicated that oleic acid was the major component of E. billardieri n-hexane extract with a total fatty acid content of 27.2% (w/w %). Duraldehyde and Spathulenol were the most abundant components of E. thyrsoideum and Isofenchol and Germacrene-D were the most abundant components of E. billardieri essential oils, respectively. Methanolic extracts and 20% and 40% Me-H2O fractions of mentioned plants indicated most antioxidant activity in line with the phenol and flavonoid contents. Essential oil of E. thyrsoideum showed strong cytotoxic effect on MCF-7 cancer cell line.Conclusion: The phytochemical analysis showed presence of phenolic compounds, flavonoids, and coumarins.
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    Evaluation of physicochemical stability of methimazole in topical formulation
    (Tabriz University of Medical Sciences, School of Pharmacy, 2025) Sarhangi, Laya; Monajjemzadeh, Farnaz
    Introduction:Melasma is a skin hyperpigmentation disorder that occurs in sun-exposed areas such as face, the first line of treatment is hydroquinone; Due to recent concerns regarding the carcinogenicity of hydroquinone in long-term use, scientists are looking for a better alternative with fewer side effects. Clinical studies on topical use of methimazole have shown that this drug can prevent melanogenesis by inhibiting peroxidase and tyrosinase enzymes.Objective: The aim of our study is to reach the optimal formulation of the topical form of methimazole and to check the stability of this formulation in different storage conditions.Materials and methods: Methimazole was prepared in two bases, cold cream and vanishing cream, and stored under 3 different temperature and humidity conditions, refrigerator temperature, room temperature, and 40 ℃for 5 months, and the remaining percentage of the drug in different time periods was determined by a validated HPLC method. In all storage conditions, the kinetic of drug reduction were fitted to zero, first, second and third order models using Excel software. The shelf life in different storage conditions was calculated based on the time required for 10% degradation of the active substance. The significance of the data was checked and reported with statistical tests and GraphPad Prism software. Physical changes such as color change were also recorded and by digital images. Results:The results of HPLC show that the residual percentage of methimazole in both cream bases has decreased significantly after 5 months, and this decrease was more at 40℃ than at other temperatures. Kinetic of drug degradation follows F1 model. By comparing shelf lives vanishing cream is more stable than cold cream. Conclusion: The topical and semi-solid form of Methimazole in Vanishing Cream base is more stable than Cold Cream.
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    Formulation and Stability Study of Iodixanol Injectable Product
    (Tabriz University of Medical Sciences, School of Pharmacy, 2024) Rahimpour, Sina; Valizadeh, Hadi; Barzegar Jalali, Mohammad
    Introduction: Stability is a crucial issue in pharmaceuticals, especially in the formulation of drug solutions. Utilizing methods and materials to enhance stability can extend the shelf life of a drug and simplify the storage of solution formulations. Goals:The aim of this study is to prepare an injectable formulation of iodixanol and assess its stability. Methods:To prepare the 320 mgI/ml iodixanol injectable solution, calcium disodium EDTA, sodium chloride, and necessary stabilizers were mixed together, and the required acidity was adjusted using a buffer to maintain a pH between 6.8 and 7.7 (with the solution pH adjusted to 7.4). The prepared solution was filtered through a 0.2-micron filter and then autoclaved at 121°C for 15 minutes. The formulated product was stored according to ICH guidelines for accelerated stability studies at 40°C and 75% humidity. Sampling was conducted at zero, one, two, four, and six months, and the remaining drug content was determined using HPLC. Results:During the six-month study period, HPLC measurement results indicated that more than 95% of the iodixanol remained stable in the injectable formulation under the specified storage conditions. At each sampling stage, physical appearance examination of the solution showed no precipitation or color change, indicating that the iodixanol injectable formulation maintained suitable physical stability throughout the study period. Conclusion:The results of this study indicate that the iodixanol injectable formulation at 320 mg/ml is chemically stable. Based on these results, a shelf life of two years can be considered for this formulation. This suggests that the developed formulation meets the necessary quality standards and can be effectively used in various diagnostic imaging procedures.
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    Formulation and stability assessment of injectable iopamidol product
    (Tabriz University of Medical Sciences, School of Pharmacy, 2024) Gheitanchian, Parichehr; Zakeri Milani, Parvin; Valizadeh, Hadi; Barzegar Jalali, Mohammad
    Introduction: Nowadays, most of the disease are diagnosed by medical imaging methods. Most imaging is done by using special drugs, we called radiopaque contrast agents.Contrast media are groups of chemical agents developed to aid in the characterization of pathology by improving the contrast resolution of an imaging modality. Specific contrast media has been developed for every structural imaging modality, and every conceivable route of administration. Iopamidol is an iodinated contrast media that is widely used in angiography, pediatric angiocardiography, myelography, cisternography CT, detecting some malignancies, and photography of non-neoplastic wounds. Although Iopamidol is widely employed in medicine in different fields, the domestic formulation of this drug is not existing.Aim: The aim of this study is formulation and evaluation the stability of iopamidol product, in order to localize this medicine, prevent foreign exchange so, it has economic importance to our country.Method: At first, iopamidol solution was produced by EDTA and tromethamine. Then the pH of the formulation was adjusted at 7.5 and the formulation was sterilized by autoclave. After autoclaving, the product was stored at 40°C and the relative humidity was 70%, and finally the stability of the formulation would be evaluated by HPLC under ICH instructions in 0, 1, 2, 4, 6 months and identification tests would be studied according to USP.Results: The produced formulation is stable in pH of 7.5 after evaluating for 6 months.Conclusion: According to our tests and investigations, by using EDTA and tromethamine, the stability of iopamidol product is improved and the product will be stable during its shelf-life.
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    Determination of blood levels of Voriconazole and Cyclosporine in allogen hematopoietic stem cell transplantation patients using green HPLC
    (Tabriz University of Medical Sciences , School of Pharmacy, 2023) Gharepasha, Sina; Nejati, Babak; Soltani, Somaieh; Ghafari, Saba
    Introduction: Voriconazole is a broad-spectrum antifungal drug of the second generation of triazoles, which is the first line for the treatment and prevention of fungal infections, and cyclosporine is a drug with the property of weakening the body's immune system to prevent graft tissue rejection. Voriconazole and cyclosporine drugs have a narrow therapeutic window and their serum levels vary among people. Therefore, it is important to evaluate their serum levels. In most of the past researches, the effects on the environment have been ignored and solvents that are dangerous have been used. Today, efforts are being made to develop analytical methods that, while having high sensitivity and speed, help to maintain human health and environmental standards.Objective: To develop an analysis method based on green HPLC to evaluate the plasma concentration of voriconazole and cyclosporine in organ transplant recipients. Method: To precipitate plasma proteins, acetonitrile was added to the microtubes in a ratio of 1:1, and after centrifugation at 10,000 rpm for 10 minutes, the upper clear liquid phase was removed. 20 µl of it was injected into the device. Analysis of voriconazole was performed by HPLC-UV with isocratic flow of water: acetonitrile ratio 1:1 and analysis of cyclosporine was performed by LC-MS with gradient flow of acetonitrile: water: 0.3% formic acid.Results and findings: The results showed that the limit of detection and limit of quantification for voriconazole drug are 0.21 and 0.63 µg/ml, respectively, and for cyclosporine are 101.15 and 306.53 ng/ml, respectively was obtained. Conclusion: Based on the obtained data and results, the developed method for identifying and measuring voriconazole and cyclosporine in plasma can be used in clinical samples and pharmacokinetic studies.
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    Phytochemical study of Phlomoides labiosa and Phlomoides binaludensis
    (Tabriz University of Medical Sciences , School of Pharmacy, 2023) Mohammadi, Samin; Nazemiyeh, Hossein; Nejad Ebrahimi, Samad; Asgharian, Parina; Delazar, Abbas
    Introduction: Phlomoides species have long been used in ethnomedicine for various purposes, such as stomach disorders and wound healing. Scope: The aim of this study was to investigate some phytochemical and biological features of two species, Phlomoides labiosa and Phlomoides binaludensis.Methods and materials: The aerial part, rhizome, and the seeds of P. labiosa and the aerial part of P. binaludensis were extracted using various solvents with increasing polarity. C18 sep-pak was applied for fractionation of methanol extracts. Further purification of fractions were done through HPLC, preparative TLC and column chromatography techniques. Structure elucidation of isolated compounds was accomplished by 1HNMR and 13CNMR and two dimensional NMR methods. Essential oil and fatty acid contents were analyzed via GC-MS method. Total phenol and flavonoid contents were assayed. Antioxidant, antibacterial, and cytotoxic properties were evaluated in all samples. After that, extract nanoliposomes were created to improve the biological effects by increasing the solubility.Results: Isolation of compounds in methanol extracts resulted elucidation of six compounds. Three compounds in methanolic extract of P. labiosa rhizome, including: Auroside, Herniarin, and Isopimpinellin. Three compounds in methanolic extract of P. binaludensis aerial part, including Chrysoeriol-4'-o-glucopyranoside, Isoscutellarein-7-O-[6″, 6'''-di-acetyl-allosyl (1→2)]-glucopyranoside, Isoscutellarein-acetylallosyl-(glucopyranoside) apiose. The results indicated that oleic acid was the major component of P. labiosa seed oil with a total fatty acid content of 37.62 (w/w %). β-caryophyllene and phytol were the most abundant components of P. labiosa and P. binaludensis essential oils, respectively. Ethyl acetate and methanol extracts indicated the antioxidant activity in line with the phenol contents. Conclusion: The phytochemical analysis showed presence of iridoids, flavonoids, and coumarins.
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    Phytochemical study of Symphytum kurdicum and Symphytum asperrimum
    (Tabriz University of Medical Sciences , School of Pharmacy, 2022) Mahmoudzadeh, Elaheh; Fathi Azad, Fatemeh; Nazemiyeh, Hossein; Hamedeyazdan, Sanaz
    Introduction: Plants of genus Symphytum have been used in different traditional medicines.Scope: Due to the importance of genus Symphytum and limited studies on the phytochemistry of Symphytum asperrimum and Symphytum kurdicum, these plants were selected for phytochemical analysis.Methods and materials: The aerial parts of plants were extracted by soxelet and Maceration methods, respectively. Ethanol extract was fractionated. Dried n-butanol extract was subjected to C18 sep-pak fractionation. Further purification was carried out of fractions by using HPLC. Structure elucidation of these compounds was accomplished by 1HNMR and 13CNMR. The components of essential oils elucidated by GC_MS. The antibacterial, antioxidant properties, and total phenol and flavonoid contents were determined. Results: GC-MS analysis indicated that the Hexafarnesyl acetone amount was high. n-butanol and ethyl acetate extracts of S. kurdicum showed the highest antioxidant ability. n-Butanol and ethyl acetate extracts of S. asperrimum indicated higher phenolic constituents. Extracts of both plants showed antimicrobial activity. Isolation of compounds in n-butanol extracts resulted elucidation of 11 compounds. There were 4 compounds in 20% sub-fraction of n-butanol fraction of 70% ethanolic extract of S. kurdicum, including: Kaempferol-3-O-glucoside (Astragalin), caffeic acid, 7-acetyl indicine and Rosmarinic acid. 4 compounds in sub-fraction 20 Percentage of n-butanol fraction of 70% ethanolic extract of S. asperrimum plant were isolated including: kaempferol-3-O-glucosyl rhamnoside, Quercetin 3-O-glucoside (Isoquercetrin), Kaempferol-7-O-glucoside and Rosmarinic acid, Also, 3 isolated compounds in sub-fraction of 40% n-butanol fraction 70% ethanolic extract of S. asperrimum were chlorogenic acid, verbascoside and forsythoside B. all of compounds were reported for the first time.Conclusion: The phytochemical analysis of two mentioned showed presence of phenolic compounds and flavnoids.
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    Gliclazide-loaded Solid Lipid Nanoparticles: preparation & Intestinal permeability investigation
    (Tabriz University of Medical Sciences , School of Pharmacy, 2023) Saei, Akbar; Valizadeh, Hadi; Mahmoudian, Mohammad; Eslambulchilar, Ziba; Zakeri Milani, Parvin
    Introduction and Background: Gliclazide, a sulfonylurea specifically used for the treatment of non-insulin-dependent diabetes mellitus. This drug exhibits slow GI absorption rate and wide inter-individual variations in absorption and bioavailability. Moreover, because of its poor water solubility, it is impossible to prepare aqueous solutions of this compound for oral or other routs of administration.Therefore, we hypothesize that these limitations could be waived by entrapping gliclazide inside a lipid carrier like Solid Lipid Nanoparticles. In the present investigation, we prepared and characterized SLNs of Gliclazide with suitable size and drug entrapment efficiency. The intestinal absorption characteristics of prepared nanoparticles assessed to estimate the in vivo bioavailability of the preparations. Aim: Preparation and in vitro and in vivo evaluation of solid lipid nanoparticles for controlled oral delivery of Gliclazide.Methods: Single-Pass Intestinal Perfusion was performed in isolated jejunal segment at SLN formulation of Gliclazide to compare intestinal permeability changes against of simple solution of gliclazide. Phenol red was used as a non-absorbable marker. Stability studies were conducted to ensure that the loss of gliclazide could be attributed to intestinal absorption. Outlet samples were analysed using the developed HPLC method and effective permeability values were calculated by respected formula.Results: The effective permeability value of Gliclazide simple solution in the jejunum was 0.00805 cm/min. Also the effective permeability values of SLN.Gliclazide nanoparticles found to be 0.0167 cm/min. The use of Solid Lipid Nanoparticles led to a significant increase in intestinal permeability of gliclazide. Discussion and conclusion: In conclusion, the high aqueous solubility of Gliclazide might be a crucial factor for its poor oral bioavailability. New techniques have shown that the use of nanoparticles like SLN can dramatically increase intestinal permeability.
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    Development of carboxylated graphene oxide as mixed hemmimicelle dispersive solid phase extraction adsorbent in methamphetamine extraction from urine
    (Tabriz University of Medical Sciences , School of Pharmacy, 2022) Daneshpouy, Sevda; Taghvimi, Arezou; Javadzadeh, Yousef; Dastmalchi, Siavoush
    Introduction: Methamphetamine is known as a critical central nervous sysytem stimulant which leads to crime among young people. Therefore, methamphetamine determination is of great interest to researchers in clinical and forensic laboratories. Aim: Carboxylated coupled ionic liquid graphene oxide nanoparticles was synthesized and applied as a new adsorbent in mixed hemmimicelle dispersive solid-phase extraction (MHMDSPE) of methamphetamine from human urine samples. Material and method: Nano graphene oxide was synthesized through modified Hummer method. The graphene oxide was carboxylated by hydrothermal method and then ionic liquid was coupled to the nanocomposite. After full characterization of the prepared adsorbent by various techniques, the nanocomposite was used in mixed hemmimicelle dispersive solid-phase extraction of methamphetamine from urine. Effective extraction parameters were optimized by one- parameter-at-a-time method. Analysis of real samples was carried out by the proposed method. Results: Carboxylated coupled ionic liquid graphene oxide nanoparticles was used for efficient extraction of methamphetamine. Carboxylated adsorbentwas characterized by different techniques such as FTIR, XRD, SEM, and zeta potential, and then optimization of effective parameters in the extraction process was performed. The synthesis method of nano adsorbent was easy, and reproducible responses were obtained in methamphetamine extraction. The calibration curve was plotted in the concentration range of 100-2000 ng/mL and validation of the method was carried out. limit of detection was 20 ng/ml. Discussion: The analysis of methamphetamine in the urine samples from addicted subjects was carried out using the prepared nanocomposite-based method followed by HPLC. Determination with the proposed method confirmed the applicability of the method in different laboratories
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    Study of Phytochemical constituents and cytotoxic effects of Halanthium rarifolium
    (Tabriz University of Medical Science, School of pharmacy, 2022) Hadavi, Nazanin; HamedYazdan, Sanaz; Nazemiyeh, Hossein; Eskandani, Morteza
    Introduction: Cancer is a global problem that accounts for almost 13% of deaths worldwide. For a number of years natural products have been a good resource of compounds against cancer. Scope: Due to the importance of medicinal properties of Halophytes and limited studies on the phytochemistry of Halanthium rarifolium, the plant was selected for phytochemical analysis along with anticancer effect. Methods and materials: The aerial parts of Halanthium rarifolium were extracted with petroleum ether, chloroform, and methanol, respectively, and then dried by rotary evaporator. Based on the preliminary results of MTT test on A549 cell line, methanolic extract was selected and fractionated by Solid Phase Extraction. After evaluating the anti-proliferative properties of sub-fractions, the methanol fraction (20% v/v) was selected for more fractionation by vacuum liquid chromatography and its sub-fractions were re-examined by MTT assay. Potentially sub-fractions were analyzed by HPLC chromatography. Results: Methanolic extract of Halanthium rarifolium had more anti-proliferative properties compared to negative control. The n-Hexan extract of the plant showed less inhibitory effect in the initial experiments than the control group and other extracts. Isolation of compounds in the most effective subfractions of methanolic extract resulted elucidation of two flavonoid glycosides. NMR spectrum data of these two compounds suggests the structures of Kaempferol 3-rutinosyle- 7-glucoside, Quercetin 3′-glucoside and Verbascoside. Conclusion: The phytochemical analysis of H. rarifolium showed presence of flavnoids. Methanolic extractions of H. rarifolium have acceptable anti-proliferative properties.