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PubMed | Food and Drug Research Center and Tehran University of Medical Sciences
Type: Journal Article | Journal: Advanced pharmaceutical bulletin | Year: 2016

Aggregation suppressing additives have been used to stabilize proteins during manufacturing and storage. Interferon-1b is prone to aggregation because of being non-glycosylated. Aggregation behavior of albumin-free formulations of recombinant IFN-1b was explored using additives such as n-dodecyl--D-maltoside, Tween 20, arginine, glycine, trehalose and sucrose at different pH.Fractional factorial design was applied to select major factors affecting aggregation in solutions. Box-Behnken technique was used to optimize the best concentration of additives and protein.Quadratic model was the best fitted model for particle size, OD350 and OD280/OD260. The optimal conditions of 0.2% n-Dodecyl--D-maltoside, 70 mM arginine, 189 mM trehalose and protein concentration of 0.50 mg/ml at pH 4 were achieved. A potency value of 91% 5% was obtained for the optimized formulation.This study shows that the combination of n-Dodecyl--D-maltoside, arginine and trehalose would demonstrate a significant stabilizing and anti-aggregating effect on the liquid formulation of interferon-1b. It can not only reduce the manufacturing costs but will also ease patient compliance.


PubMed | Tehran University of Medical Sciences, Food and Drug Research Center, Shahid Beheshti University of Medical Sciences and Baqiyatallah Medical Sciences University
Type: Journal Article | Journal: Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences | Year: 2015

Formoterol and salmeterol are two long-acting 2-agonists given by inhalation, with bronchodilating effects lasting for at least 12 h after a single administration. Formoterol has a faster onset of action compared with salmeterol. The aim of this study was to perform a systematic review and meta-analysis on the data published from previous review in order to calculate pooled estimates of effectiveness and safety assessment of formoterol and salmeterol in treatment of patients with asthma.In this study, we conducted an electronic search for medical citation databases including Cochrane, PubMed, Scopus, PsycInfo, and IranMedex. Besides manual search of the databases that record randomized clinical trials, conference proceedings, and journals related to asthma were included. Studies were evaluated by two independent people based on inclusion and exclusion criteria, and the common outcomes of studies were entered into the RevMan 5.0.1 software, after evaluation of studies and extraction of data from them; and in cases where there were homogeneous studies, meta-analysis was performed, and for heterogeneous studies, the results were reported qualitatively.Of the 1539 studies initially found, 13 were included in the study. According to the meta-analysis conducted, no significant difference was found between the inhalation of formoterol 12 g and salmeterol 50 g in the two outcomes of mean forced expiratory volume 1 s (FEV1), 12 h after inhalation of medication and Borg score (A frequently used scale for quantifying breathlessness) after inhalation of medication. In addition, salmeterol was more effective than formoterol in the two outcomes of percent decrease in FEV1 after inhalation of methacholine and the number of days without an attack. Since the two outcomes of FEV1 30-60 min after inhalation of medication and morning peak expiratory flow after inhalation of medication were heterogeneous, they had no meta-analysis capabilities, and its results were reported qualitatively.The data from included studies shows that, more efficacy has been achieved with Salmeterol, especially in some outcomes such as the percent decrease in FEV1 after inhalation of Methacholine, and the number of days without an attack; and therefore, the administration of Salmeterol seems to be beneficial for patients, compared with Formoterol.


Shafizadeh M.,Tehran University of Medical Sciences | Rajaba A.,Tehran University of Medical Sciences | Imran Khan M.,Tehran University of Medical Sciences | Ostadhadi S.,Tehran University of Medical Sciences | And 2 more authors.
European Journal of Pharmacology | Year: 2014

Pioglitazone is a member of peroxisome proliferator-activated receptor gamma (PPARγ) agonists, particularly used in management of type II diabetes. However it also has effects in some dermatological disorders. The current study was designed to investigate the effects of oral administration of pioglitazone and the association of nitric oxide, in serotonin-induced scratching in mice. In order to produce the scratching activity, serotonin (141 nm/site) was administered intradermally in the nape of the neck. Pioglitazone in concentrations of 10, 20, 40 and 80 mg/kg, was peroral administered (p.o) as a single dose, 4 h before the serotonin injection. PPAR-γ antagonist, GW9662 (2 mg/kg, i.p); a non-specific nitric oxide synthase (NOS) inhibitor, NG-nitro-l-arginine methyl ester (l-NAME; 1 mg/kg, i.p); or a nitric oxide precursor, l-arginine (100 mg/kg, i.p.); adminstrated 15 min before pioglitazone were analyzed for anti-scratching activity. Results obtained showed that pioglitazone (40 and 80 mg/kg, p.o) reduced the scratching in a dose-dependent manner. GW9662 inverted the anti-scratching effect of pioglitazone (80 mg/kg). Acute dose of l-NAME (1 mg/kg, i.p) also prevented the anti-scratching property of pioglitazone (80 mg/kg, p.o); although l-arginine was used in sub-effective dose (100 mg/kg, i.p), however it potentiated the anti-scratching behavior when co-injected with pioglitazone (20 mg/kg, p.o). The results indicate that acute pioglitazone has an anti-scratching effect on serotonin-induced scratching in mice. It is concluded that anti-scratching outcome of acute pioglitazone is initiated via activation of PPAR-γ receptor and to some extent by the NO pathway. © 2014 Elsevier B.V. All rights reserved.


PubMed | Food and Drug Research Center and Tehran University of Medical Sciences
Type: | Journal: European journal of pharmacology | Year: 2014

Pioglitazone is a member of peroxisome proliferator-activated receptor gamma (PPAR) agonists, particularly used in management of type II diabetes. However it also has effects in some dermatological disorders. The current study was designed to investigate the effects of oral administration of pioglitazone and the association of nitric oxide, in serotonin-induced scratching in mice. In order to produce the scratching activity, serotonin (141 nm/site) was administered intradermally in the nape of the neck. Pioglitazone in concentrations of 10, 20, 40 and 80 mg/kg, was peroral administered (p.o) as a single dose, 4 h before the serotonin injection. PPAR- antagonist, GW9662 (2 mg/kg, i.p); a non-specific nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 1 mg/kg, i.p); or a nitric oxide precursor, L-arginine (100 mg/kg, i.p.); adminstrated 15 min before pioglitazone were analyzed for anti-scratching activity. Results obtained showed that pioglitazone (40 and 80 mg/kg, p.o) reduced the scratching in a dose-dependent manner. GW9662 inverted the anti-scratching effect of pioglitazone (80 mg/kg). Acute dose of L-NAME (1 mg/kg, i.p) also prevented the anti-scratching property of pioglitazone (80 mg/kg, p.o); although L-arginine was used in sub-effective dose (100 mg/kg, i.p), however it potentiated the anti-scratching behavior when co-injected with pioglitazone (20 mg/kg, p.o). The results indicate that acute pioglitazone has an anti-scratching effect on serotonin-induced scratching in mice. It is concluded that anti-scratching outcome of acute pioglitazone is initiated via activation of PPAR- receptor and to some extent by the NO pathway.


Bazhdanzadeh S.,Alzahra University | Talebpour Z.,Alzahra University | Adib N.,Food and Drug Research Center | Aboul-Enein H.Y.,National Research Center of Egypt
Journal of Separation Science | Year: 2011

A sensitive and reproducible stir bar sorptive extraction and HPLC-UV detection method was used for the therapeutic drug monitoring of chlorpromazine and trifluoperazine in human serum. The separation was achieved using a C 18 column. The mobile phase consisted of methanol/sodium acetate buffer (pH 4.1; 0.1 M) (95:5, v/v) including 0.5% triethylamine. This miniaturized method can result in faster analysis, lower solvent consumption and less workload per sample while maintaining or even improving sensitivity. In the second part, stir bar sorptive extraction/HPLC-UV method was optimized by a chemometrics approach. An experimental design was therefore used to evaluate the statistically influential and/or interacting factors, among those described in the literature, and to find the best extraction and desorption conditions. Optimal sample volume of 1 mL, extraction time of 24 min at 31°C with pH 8.1 were obtained in a screening 25 half fractional factorial design followed by a Box-Behnken design. For the desorption conditions, a Box-Behnken design showed that the best conditions were 150 μL mobile phase for 20 min at 50°C. The optimized method was repeatable (CV<10%, linear (LOQ-500 ng/mL)), with the LOQs equal to 0.7 and 1.5 ng/mL for chlorpromazine and trifluoperazine, respectively. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Talebpour Z.,Alzahra University | Taraji M.,Alzahra University | Adib N.,Food and Drug Research Center
Journal of Chromatography A | Year: 2012

This article presents a method employing stir bar coated with a film of poly (methyl methacrylate/ethyleneglycol dimethacrylate) (PA-EG) and polydimethylsiloxane (PDMS) in combination with liquid desorption (LD) using ionic liquid, followed by high performance liquid chromatography (HPLC) equipped with ultraviolet (UV) detection for the determination of carvedilol in human serum samples. Stir bar sorptive extraction (SBSE) variables, such as desorption and extraction time and temperature, desorption solvent and pH of the matrix were optimized, in order to achieve suitable analytical sensitivity in a short period of time. Also, the concentration effect of 1-methyl-3-octylimidazolium tetrafluoroborate [Omim][BF4] ionic liquid on the efficiency of LD was investigated. A comparison between PA-EG/SBSE and PDMS/SBSE was made by calculating the experimental recovery and partition coefficient (K), where PA-EG phase demonstrated to be an excellent alternative for the enrichment of the carvedilol from serum samples. The effect of [Omim][BF4] on carryover was studied and no carryover was observed. Under optimized experimental conditions, the analytical performance showed excellent linear dynamic range, with correlation coefficients higher than 0.999 and limits of detection and quantification of 0.3 and 1.0ngmL -1, respectively. Intra- and inter-day recovery ranged from 94 to 103% and the coefficients of variations were less than 3.2%. The proposed method was shown to be simple, highly sensitive and suitable for the measurement of trace concentration levels of carvedilol in biological fluid media. © 2012 Elsevier B.V.


PubMed | National Research Center of Egypt, Food and Drug Research Center and Alzahra University
Type: Journal Article | Journal: Journal of separation science | Year: 2016

A new monolithic coating based on vinylpyrrolidone-ethylene glycol dimethacrylate polymer was introduced for stir bar sorptive extraction. The polymerization step was performed using different contents of monomer, cross-linker and porogenic solvent, and the best formulation was selected. The quality of the prepared vinylpyrrolidone-ethylene glycol dimethacrylate stir bars was satisfactory, demonstrating good repeatability within batch (relative standard deviation < 3.5%) and acceptable reproducibility between batches (relative standard deviation < 6.0%). The prepared stir bar was utilized in combination with ultrasound-assisted liquid desorption, followed by high-performance liquid chromatography with ultraviolet detection for the simultaneous determination of diazepam and nordazepam in human plasma samples. To optimize the extraction step, a three-level, four-factor, three-block Box-Behnken design was applied. Under the optimum conditions, the analytical performance of the proposed method displayed excellent linear dynamic ranges for diazepam (36-1200 ng/mL) and nordazepam (25-1200 ng/mL), with correlation coefficients of 0.9986 and 0.9968 and detection limits of 12 and 10 ng/mL, respectively. The intra- and interday recovery ranged from 93 to 106%, and the relative standard deviations were less than 6%. Finally, the proposed method was successfully applied to the analysis of diazepam and nordazepam at their therapeutic levels in human plasma. The novelty of this study is the improved polarity of the stir bar coating and its application for the simultaneous extraction of diazepam and its active metabolite, nordazepam in human plasma sample. The method was more rapid than previously reported stir bar sorptive extraction techniques based on monolithic coatings, and exhibited lower detection limits in comparison with similar methods for the determination of diazepam and nordazepam in biological fluids.


PubMed | National Research Center of Egypt, Food and Drug Research Center and Alzahra University
Type: Journal Article | Journal: Journal of chromatographic science | Year: 2015

A sensitive, selective and simple method for the simultaneous determination of carvedilol enantiomers in aqueous solution has been developed using stir bar sorptive extraction (SBSE) followed by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. This method is based on the reaction of carvedilol enantiomers with (-)-menthyl chloroformate (MCF) after extraction by the SBSE method to produce diastereomeric derivatives. The separation was achieved by use of a C18 analytical column and the influence of mobile phase composition on the enantioseparation of carvedilol was studied. The applicability of two sorptive phases, poly(methyl methacrylate/ethyleneglycol dimethacrylate) (PA-EG) and polydimethylsiloxane, were tested for extraction of carvedilol enantiomers from aqueous samples. The obtained results showed excellent linear dynamic ranges and precisions for each of them. The least limit of detection for (S)- and (R)-carvedilol obtained 8 and 11 g L(-1), respectively, using the PA-EG sorptive phase. Inter- and intra-mean recoveries were also satisfactory, ranging from 98 to 103%, with coefficient of variation in the range of 1-5% at three fortified levels using a PA-EG coated stir bar. The proposed SBSE (PA-EG)-MCF derivatization-HPLC-UV method was successfully applied to enantioselective analysis of carvedilol in water and pharmaceutical dosages, confirming the application of this method.


PubMed | Food and Drug Research Center
Type: Journal Article | Journal: Iranian journal of public health | Year: 2013

Clinical Trial Committee (CTC) has been established in Food and Drug Organization (FDO), in 2003 to assure efficacy and safety of all types of medicinal products which are meant to be registered in Iran Drug List and/or obtain market authorization.All clinical trial files, meeting minutes and databases in CTC secretariat in FDO were reviewed. Relevant information and data extracted, analyzed and reported.Total number of clinical trial (CT) files received by CTC, in 2011, was 76 cases: 21 CT protocols, 45 CT reports and 10 requests for importation of investigational new medicinal products (IMPs). Number of CT files received for herbal and natural products was 8 cases while CT files reviewed for vaccines and biological products was 50; 66% of all CT files received. Local industries sponsored 28 CT studies while 47 studies were supported by multinational/foreign companies. Of all CT files reviewed, 54 cases accounted for phase III CTs and 20 cases for phase IV and periodic safety updated reports (PSUR). With respect to the decisions made by CTC in 2011, 23 out of 45 CT reports were approved and the number of clinical trial authorizations (CTA) issued were 11; 52% of all CT protocols reviewed.Results presented in this report are indicative of a positive trend in compliance of pharmaceutical industries and clinical research groups to national regulations of CTs and IR-GCP. Effective communication with different parties involved in regulatory and industry sides of CTs will further enhance conducting quality CTs.


PubMed | Food and Drug Research Center
Type: Journal Article | Journal: Acta medica Iranica | Year: 2013

Breast cancer is the most commonly diagnosed invasive malignancy and first leading cause of cancer-related deaths in Iranian women. Based on silymarins unique characteristics, its application in chemotherapy combined with doxorubicin can be effective to enhance the efficacy together with a reduced toxicity on normal tissues. The present study focus on evaluate the efficacy of silymarin in combination with doxorubicin, on viability and apoptosis of estrogen-dependent breast carcinoma cell line (MCF-7). After being cultured, MCF-7 cells were divided into 8 groups and treated as follows: 1st group received 75 g silymarin, groups 2, 3, and 4 were treated with 10, 25, and 50 nM doxorubicin, respectively, and groups 5, 6, and 7 respectively received 10, 25, and 50 nM doxorubicin as well as 75 g silymarin. Viability percentage and apoptosis of the cells were assessed with Trypan Blue staining after 16, 24, and 48 hours. Silymarin has a synergistic effect on the therapeutic potential of doxorubicin. Use of silymarin in combination with doxorubicin can be more effective on the therapeutic potential of doxorubicin and decreases its dose-limiting side effects.

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