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Advanced Pharmaceutical Bulletin - Volume:4 Issue: 4, Dec 2014

Advanced Pharmaceutical Bulletin
Volume:4 Issue: 4, Dec 2014

  • تاریخ انتشار: 1393/06/05
  • تعداد عناوین: 15
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  • Behzad Mansoori, Siamak Sandoghchian Shotorbani, Behzad Baradaran Pages 313-321
    In todays’ environment, it is becoming increasingly difficult to ignore the role of cancer in social health. Although a huge budget is allocated on cancer research every year, cancer remains the second global cause of death. And, exclusively, less than 50% of patients afflicted with advanced cancer live one year subsequent to standard cancer treatments. RNA interference (RNAi) is a mechanism for gene silencing. Such mechanism possesses uncanny ability in targeting cancer-related genes. A majority of gene products involved in tumorigenesis have recently been utilized as targets in RNAi based therapy. The evidence from these studies indicates that RNAi application for targeting functional carcinogenic molecules, tumor resistance to chemotherapy and radiotherapy is required in today’s cancer treatment. Knock downing of gene products by RNAi technology exerts antiproliferative and proapoptotic effects upon cell culture systems, animal models and in clinical trials in the most studies. The recognition of RNAi mechanism and the progress in this field leaded several new RNAi-based drugs to Clinical Trial phases. This has also developed genome based personalized cancer therapeutics. Hopefully, this type of treatment will work as one of the efficient one for cancer patients.
  • Fatemeh Kazemi, Lomedasht, Mahdi Behdani, Kamran Pooshang, Bagheri, Mahdi Habibi, Anbouhi, Mohsen Abolhassani, Hossein Khanahmad, Delavar Shahbazzadeh, Hassan Mirzahoseini Pages 323-328
    Purpose
    Angiogenesis or formation of new blood vessels is an essential process for tumor growth, invasion and metastasis. Vascular Endothelial Growth Factor (VEGF) and its receptors play an important role in angiogenesis-dependent tumors. VEGF-A is the most important factor in angiogenesis process. Human VEGF-A gene consists of eight exons that undergoes alternative exon splicing and produce five different proteins consisting of 121, 145, 165, 189 and 206 amino acids (named VEGF121, VEGF145, VEGF165, VEGF189, and VEGF206).
    Methods
    In this study, VEGF121 gene synthesized and cloned into the pET-26b plasmid. The recombinant plasmid was transferred into appropriate expression strain of BL-21. Expression of VEGF121 induced by IPTG (Isopropyl β-D-1-thiogalactopyranoside) and confirmed by SDS-PAGE and Western-Blotting. Recombinant VEGF121 was purified by nickel affinity chromatography. HUVECs (Human Umbilical Vein Endothelia Cells) cells were isolated from umbilical vein and the effect of VEGF121 on tube formation of endothelial cells was investigated.
    Results
    SDS-PAGE and Western-Blotting results verified the purification of VEGF121. The final yield of recombinant protein was about 5mg per liter. Endothelial cell tube formation assay results showed that VEGF121 leads to tube formation of endothelial cell on matrix and induces angiogenesis in vitro.
    Conclusion
    Recombinant VEGF121 is important factor in tube formation of endothelial cell, so it could be used in different cancer researches and angiogenesis assay.
    Keywords: VEGF121, Angiogenesis, Endothelial tube formation assay
  • Farnaz Monajjemzadeh, Fatemeh Ebrahimi, Parvin Zakeri, Milani, Hadi Valizadeh Pages 329-328
    Purpose
    In this research the effect of vitamin B1 and B6 on cyanocobalamin stability in commercial light protected parenteral formulations and upon adding stabilizing agents will be investigated and best formulation composition and proper storage condition will be introduced.
    Methods
    In this research some additives such as co solvents and tonicity adjusters, surfactants, antioxidants and chelating agents as well as buffer solutions, were used to improve the stability of the parenteral mixed formulations of B12 in the presence of other B vitamins (B1 and B6). Screening tests and accelerated stability tests were performed according to ICH guidelines Q1A (R2).
    Results
    Shelf life evaluation revealed the best formulation and the proper storage condition. The results indicated the first kinetic models for all tested formulations and the optimum pH value was determined to be 5.8. There was no evidence of B12 loss when mixed with B1 and B6 in a medical syringe at room temperature for maximum of 8 hours.
    Conclusion
    It is necessary to formulate vitamin B12 mixed parenteral solutions using proper phosphate buffers (pH=5.8) and to indicate “Store in refrigerator” on the mixed parenteral formulations of vitamin B12 with other B vitamins, which has not been expressed on the label of tested Brand formulations at the time of this study.
    Keywords: Parenteral, Stability, Incompatibility, Light protected, Degradation Kinetics
  • Fariba Mirzaie Bavil, Gisou Mohaddes, Hadi Ebrahimi, Rana Keyhanmanesh, Rafigheh Ghiyasi, Mohammad Reza Alipour Pages 339-343
    Purpose
    Hypoxia is a condition of decreased availability of oxygen. To adapt hypoxia,some changes in blood cells occur in the body. The aim of this study was to evaluate theeffect of ghrelin on different types of blood cell in normobaric hypoxia situation.
    Methods
    Thirty-two animals were divided in 4 groups (n=8): control (C), ghrelin (G),hypoxia (H), and hypoxic animals that received ghrelin (H+G). Hypoxia (11%) was inducedby an Environmental Chamber System GO2 Altitude. Animals in ghrelin groups received asubcutaneous injection of ghrelin (150 μg/kg/day) for 14 days.
    Results
    Our results show that ghrelin significantly (p<0.05) increased RBC and Hct levels,whereas it significantly (p<0.05) decreased lymphocytes in the blood. RBC, Hct, Hbconcentration, platelet and MCV increased significantly (p<0.05) in hypoxic conditions butlymphocytes, monocytes and Polymorphonuclears did not show any significant changes.Platelets had a significant (p<0.05) decrease in hypoxic conditions and ghrelinadministration in hypoxic conditions could increase lymphocyte levels significantly(p<0.05).
    Conclusion
    Effect of ghrelin on blood cells could be related to blood oxygen level. Ghrelinin normal oxygen conditions increases RBC and Hct
    Keywords: Blood cells, Ghrelin, Hypoxia, Ra
  • Mohammad Javad Khodayar, Milad Kiani, Ali Asghar Hemmati, Anahita Rezaie, Mohammad Rahim Zerafatfard, Mohammad Reza Rashidi, Mehdi Goudarzi Pages 345-349
    Purpose
    Pulmonary fibrosis is a potentially lethal inflammatory disease and there has been no effective medication for this progressive disease up to now. As a model, different therapeutic approaches have been applied for paraquat-induced pulmonary injury and fibrosis. Atorvastatin besides cholesterol-lowering effects possesses anti-inflammatory and anti-oxidant properties. The current study was designed to investigate the preventive anti-fibrotic effects of atorvastatin on paraquat-induced pulmonary fibrosis in rats.
    Methods
    The rats were randomly divided into five experimental groups. Group I, control group (saline), group II received a single oral dose of 20 mg/kg paraquat with no treatment and III, IV and V groups received atorvastatin at the doses of 10, 20, and 40 mg/kg/day orally one week before and three weeks after paraquat administration, respectively. The rats were sacrificed 21 days after paraquat. Lung hydroxyproline and serum levels of malondialdehyde (MDA) were determined and lung indices and semi-quantitative histopathological changes were evaluated.
    Results
    Paraquat could significantly increase the serum MDA and lung hydroxyproline levels. Elevated content of tissue hydroxyproline and serum levels of malondialdehyde induced by paraquat, attenuated by atorvastatin at the doses of 10, 20 and 40 mg/kg. Furthermore, histopathological findings and the amount of lung indices showed the beneficial preventive role of atorvastatin in rat pulmonary fibrosis induced by paraquat.
    Conclusion
    In conclusion, the present data show that atorvastatin alleviate the toxic effects of paraquat under the experimental circumstances and may be a useful agent in cases who are in contact or poisoned with paraquat.
    Keywords: Paraquat, Pulmonary fibrosis, Atorvastatin, Rat
  • Pooria Taghavi Moghaddam, Mohammad Reza Pipelzadeh, Sholeh Nesioonpour, Nader Saki, Saeed Rezaee Pages 351-358
    Purpose
    The aim of this study was to select the best calibration model for determination of propofol plasma concentration by high-performance liquid chromatography method.
    Methods
    Determination of propofol in plasma after deproteinization with acetonitrile containing thymol (as internal standard) was carried out on a C18 column with a mixture of acetonitrile and trifluoroacetic acid 0.1% (60:40) as mobile phase which delivered at the flow rate of 1.2 mL/minute. Fluorescence detection was done at the excitation and emission wavelengths of 276 and 310 nm, respectively. After fitting different equations to the calibration data using weighted regression, the adequacy of models were assessed by lack-of-fit test, significance of all model parameters, adjusted coefficient of determination (R2adjusted) and by measuring the predictive performance with median relative prediction error and median absolute relative prediction error of the validation data set.
    Results
    The best model was a linear equation without intercept with median relative prediction error and median absolute relative prediction error of 4.0 and 9.4%, respectively in the range of 10-5000 ng/mL. The method showed good accuracy and precision.
    Conclusion
    The presented statistical framework could be used to choose the best model for heteroscedastic calibration data for analytes like propofol with wide range of expected concentration.
    Keywords: Propofol, High, performance liquid chromatography, Calibration, Heteroscedasticty, Weighted least squares regression
  • Mostafa Asadpoor, Masoud Ansarin, Mahboob Nemati Pages 359-362
    Purpose
    Fruit juice is a nutrient rich food product with a direct connection to public health. The purpose of this research was to determine the amino acid profile of juices and provide a quick and accurate indicator for determining their authenticity.
    Methods
    The method of analysis was HPLC with fluorescence detector and pre-column derivatization by orthophtaldialdehyde (OPA). Sixty-six samples of fruit juices were analyzed, and fourteen amino acids were identified and determined in the sampled fruit juices. The fruit samples used for this analysis were apples, oranges, cherry, pineapple, mango, apricot, pomegranate, peach and grapes.
    Results
    The results showed that 32% of samples tested in this study had a lower concentrate percentage as compared to that of their labels and/or other possible authenticity problems in the manufacturing process. The following samples showed probable adulteration: four cherry juice samples, two pomegranate juice samples, one mango, three grape, four peach, seven orange, two apple and one apricot juice samples.
    Conclusion
    In general, determining the amount of amino acids and comparing sample amino acids profiles standard values seems to be an indicator for quality control. This method can the regulatory agencies with a tool, to help produce a healthier The aim of this study is the analytical control of the fruit juice composition is becoming an important issue, and HPLC can provide an important and essential tool for more accurate research as well as for routine analysis.
    Keywords: Fruit juice, Amino acid, HPLC, Adulteration, Authenticity
  • Alireza Rouhani, Ali Tabrizi, Asghar Elmi, Naghi Abedini, Fardin Mirza Tolouei Pages 363-367
    Purpose
    Pain is one of the most important factors adversely affecting clinical outcomes of operated patients. The present study aims at evaluating effects of preoperative COX2 non-steroidal anti-inflammatory inhibitors on pain mitigation and performance of patients with shoulder rotator cuff tear.
    Methods
    This case-control study was conducted on 60 patients suffering from rotator cuff injury candidate for arthroscopic repair. The patients were classified in two parallel and matched groups. One group (case group) was treated using Celecoxib (200mg/12h) started 48 hours before surgery and continued for 10 days after operation. In the control group, the placebo was prescribed in the same way. Postoperative pain, side effects, sleep disturbance, and short-term outcomes were compared between two groups using DASH questionnaire.
    Results
    Postoperative pain in the Celecoxib group significantly decreased in comparison with the control one. The difference was statistically meaningful (P<0.001). Well motion ability was seen in 80% of patients of the Celecoxib group. It was 26.6% in the placebo group since pain inhibited them from exercising more motions. In this regard, there was a statistically meaningful difference between these two groups (P=0.02). Sleep disturbance was meaningfully at higher levels in the placebo group (P=0.001). Following up the patients for three months, it was made clear that performance of the Celecoxib group was better than that of the placebo one.
    Conclusion
    COX2 inhibitors are well efficient in patients’ pain management after arthroscopic rotator cuff repair surgery. It results in less life complications, less sleep disturbances, improvement of patients’ short-term clinical outcome, and more quick recovery.
    Keywords: Postoperative pain control, Rotator cuff tear, Non, steroidal anti, inflammatory drugs, Celecoxib
  • Shahram Emami, Hadi Valizadeh, Ziba Islambulchilar, Parvin Zakeri, Milani Pages 369-374
    Purpose
    The aim of the present investigation was preparation and characterization of sirolimus solid dispersions by solvent evaporation technique to improve its dissolution properties.
    Methods
    Polyvinylpyrrolidone (PVP), Poloxamer 188 and Cremophore RH40 were used to prepare the solid dispersions of sirolimus. In vitro dissolution study using USP type I apparatus, were performed in distilled water (containing SLS 0.4%) for pure sirolimus, physical mixtures, Rapamune and prepared solid dispersions. The characterization of solid dispersions was performed using Fourier Transform Infrared (FTIR) Spectroscopy and Differential Scanning Calorimetry (DSC).
    Results
    More than 75% of sirolimus was released within 30 minutes from all prepared solid dispersions. The dissolution rate of all prepared solid dispersion powders were more than physical mixtures. The absence of sirolimus peak in the DSC spectrum of solid dispersions indicated the conversion of crystalline form of sirolimus into amorphous form. The results from FT-IR spectroscopy showed that there was no significant change in the FT-IR spectrum of solid dispersions indicating absence of well-defined interaction between drug and carriers.
    Conclusion
    It was concluded that solid dispersion method, using PVP, Poloxamer 188 and Cremophore RH40 can improve dissolution rate of sirolimus.
    Keywords: Rapamycin, Poor soluble, Immunosuppressive, Dissolution enhancement
  • Mostafa Feghhi, Fereydoun Farrahi, Mohammadreza Abbaspour, Akbar Takhtaeian Pages 375-378
    Purpose
    To evaluate the effect of oral calcium dobesilate (Doxium) on macular thickness in clinically significant macular edema (CSME).
    Methods
    Overall, 71 eyes of 40 patients with non-proliferative diabetic retinopathy and clinically significant macular edema were included. All patients were received laser treatment for macular edema. Coherence optical tomography was used to determine the retinal thickness. Patients were randomized into two groups: group A received three Doxium capsule daily and group B received three placebo capsule daily for six months.
    Results
    The mean macular thickness before and after treatment in the group A was 340 and 257 micrometers respectively (24.5% reduced), and in the group B was 336 micrometers and 263 micrometers respectively (21.5% reduced). Macular thickness significantly decreased after treatment in both groups and the reduction in group A is higher but the difference of reduction between the two groups was not statistically significant (P>0.05).
    Conclusion
    In respect to the effect of adding oral Doxium to Laser Photocoagulation on the macular thickness in patients with diabetic macular edema, this study showed no statistically significant difference between Doxium and placebo.
    Keywords: Calcium dobesilate (Doxium), Clinically significant macular edema (CSME), Macular thickness Diabetic retinopathy, Macular photocoagulation (MPC)
  • Mashiur Rahman, Farzana Prianka, Mohammad Shohel Abdul Mazid Pages 379-383
    Purpose
    The aim of this study was to characterize the binding profile as well as to notify the interaction of palmitic acid with metoprolol succinate at its binding site on albumin.
    Methods
    The binding of metoprolol succinate to bovine serum albumin (BSA) was studied by equilibrium dialysis method (ED) at 27°C and pH 7.4, in order to have an insight in the binding chemistry of the drug to BSA in presence and absence of palmitic acid. The study was carried out using ranitidine as site-1 and diazepam as site-2 specific probe.
    Results
    Different analysis of binding of metoprolol succinate to bovine serum albumin suggested two sets of association constants: high affinity association constant (k1 = 11.0 x 105 M-1) with low capacity (n1 = 2) and low affinity association (k2 = 4.0×105 M-1) constant with high capacity (n2 = 8) at pH 7.4 and 27°C. During concurrent administration of palmitic acid and metoprolol succinate in presence or absence of ranitidine or diazepam, it was found that palmitic acid displaced metoprolol succinate from its binding site on BSA resulting reduced binding of metoprolol succinate to BSA. The increment in free fraction of metoprolol succinate was from 26.27% to 55.08% upon the addition of increased concentration of palmitic acid at a concentration of 0×10-5 M to 16×10-5 M. In presence of ranitidine and diazepam, palmitic acid further increases the free fraction of metoprolol succinate from 33.05% to 66.95% and 40.68% to 72.88%, respectively.
    Conclusion
    This data provided the evidence of interaction at higher concentration of palmitic acid at the binding sites on BSA, which might change the pharmacokinetic properties of metoprolol succinate.
    Keywords: Metoprolol succinate, Palmitic acid, Bovine serum albumin, Equilibrium dialysis, Binding sites
  • Jafar Akbari, Majid Saeedi, Katayoun Morteza, Semnani, Hamidreza Kelidari, Maryam Lashkari Pages 385-390
    Purpose
    Bioadhesive polymers play an important role in biomedical and drug delivery applications. The aim of this study is to develop a sustained- release tablet for local application of Cetylpyridinium Chloride (CPC). This delivery system would supply the drug at an effective level for a long period of time, and thereby overcome the problem of the short retention time of CPC and could be used for buccal delivery as a topical anti-infective agent.
    Methods
    CPC bioadhesive tablets were directly prepared using 7 mm flat-faced punches on a hydraulic press. The materials for each tablet were weighted, introduced into the die and compacted at constant compression pressure. The dissolution tests were performed to the rotation paddle method and the bioadhesive strength of the tablets were measured.
    Results
    The results showed that as the concentration of polymer increased, the drug release rate was decreased. Also the type and ratio of polymers altered the release kinetic of Cetylpyridinium Chloride from investigated tablets. The bioadhesion strength increased with increasing the concentration of polymer and maximum bioadhesion strength was observed with HPMC K100M.
    Conclusion
    The selected formulation of CPC bioadhesive tablet can be used as a suitable preparation for continuous release of CPC with appropriate bioadhesion strength.
    Keywords: Cetylpyridinium Chloride, HPMC K100M, Carbopol 974P, Polycarbophill, Bioadhesive
  • Mohammad Reza Siahi, Shadbad, Saeed Ghanbarzadeh, Mohammad Barzegar, Jalali, Hadi Valizadeh, Alireza Taherpoor, Ghobad Mohammadi, Azim Barzegar, Jalali, Khosro Adibkia Pages 391-399
    Purpose
    The purpose of this study was to prepare and characterize solid dispersion formulation of furosemide to enhance dissolution rate.
    Methods
    Solid dispersions with different drug: carrier ratios were prepared by cogrinding method using crospovidone and microcrystalline cellulose as carrier. The physical state and interactions between the drug and carrier were characterized by Fourier transform infrared spectroscopic (FT-IR) and X ray diffraction (XRD).
    Results
    Solid dispersions (especially with drug: Carrier ratio of 1:2) showed a higher dissolution rate than their respective physical mixture and pure furosemide. Dissolution rate in pH 5.8 was also higher than pH 1.2. The XRD analysis showed that crystalline form was changed to the amorphous state in the solid dispersions. FT-IR analysis did not show any physicochemical interactions in the solid dispersion formulations. Release kinetic of formulations were fitted best to the Weibull and Wagner log probability (linear kinetic) as well as suggested 2 and Gompertz (non-linear kinetic) models.
    Conclusion
    The dissolution properties of furosemide were improved with the use of hydrophilic carriers in solid dispersions due to change in the crystalline form of the drug and more intimate contact between drug and carriers which was dependent on the type and ratio of carrier as well as dissolution medium pH.
    Keywords: Furosemide, Solid dispersion, Dissolution rate, Release kinetic
  • Muhammad Nazrul Somchit, Faizah Sanat, Gan Eng Hui, Shahrin Iskandar Wahab, Zuraini Ahmad Pages 401-404
    Purpose
    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model.
    Methods
    Mice were dosed intraperitoneally with mefenamic acid either as a single dose(100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil) or as single daily doses for 14 days(50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day). Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN) and creatinine activities were measured.
    Results
    Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine.
    Conclusion
    Results from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.
    Keywords: NSAIDS, Mefenamic acid, Nephrotoxicity, Histopathology
  • Mathrusri Annapurna Mukthinuthalapati, Venkatesh Bukkapatnam, Sai Pavan Kumar Bandaru Pages 405-411
    Purpose
    A simple stability indicating reverse phase liquid chromatographic method was developed for the simultaneous determination of rosuvastatin and ezetimibe in pharmaceutical formulations.
    Methods
    Best chromatographic response was achieved with C18 column (250 X 4.6 mm, 5μm) with photo diode array (PDA) detector. The mobile phase was composed of a mixture of sodium acetate buffer (pH 4.0) and acetonitrile (30:70, %v/v) with a flow rate of 1.2 mL/min. (UV detection at 254 nm). Rosuvastatin and ezetimibe were subjected to stress conditions of degradation and the method was validated as per ICH guidelines.
    Results
    The method shows linearity over a concentration range of 0.5–250 μg/ml for both rosuvastatin (r2 = 0.9993) and ezetimibe (r2 = 0.9996). Both the drugs are highly sensitive towards alkaline conditions in comparison to other stress conditions.
    Conclusion
    The proposed method can be successfully applied to perform long-term and accelerated stability studies for the simultaneous determination of rosuvastatin and ezetimibe in pharmaceutical formulations.
    Keywords: RP, HPLC, Rosuvastatin, Ezetimibe, Isocratic, ICH guidelines