Iranian Journal of Pharmaceutical Research
Volume:12 Issue: 1, Winter 2013

The constant endeavors of a group of pharmacists graduated in different areas in Shahid Beheshti University of Medical Sciences has led to the foundation of one of the most prestigious pharmacy schools, not only within Iran, but among Eastern Asian pharmacy Schools. We are proud to state that we have been successfully carrying on a great share of the pharmaceutical advancements in many various relevant fields. This honor would have never been obtained without the on-going supports rendered by the University’s officials, Ministry of Health, and the generous efforts of our treasured faculty members.

The current methods for treatment of cancers are inadequate and more specific methods such as gene therapy are in progress. Among different vehicles, cationic liposomes are frequently used for delivery of genetic material. This investigation aims to prepare and optimize DOTAP cationic liposomes containing an antisense oligonuclotide (AsODN) against protein kinase C alpha in non-small cells lung cancer (NSCLC).To perform this investigation, two different methods of ethanol injection and thin film hydration were used to prepare AsODN-loaded DOTAP liposomes. The formulated liposomes were then evaluated for their morphology, particle size, zeta potential and encapsulation efficiency, and the best formulation was chosen. In-vitro growth inhibitory effect of encapsulated ODN on A549 cells were evaluated by MTT and colonogenic assay. The physical and serum stability of liposomal ODN were also evaluated. Thin film hydration method resulted in large liposomes that required downsizing by extrusion with an encapsulation efficiency of 13%. Ethanol injection, in a single step gave liposomes with a small size of 115 nm and an encapsulation efficiency of around 90% which were physically stable for 6 months. The optimized liposome could protect oligonucleotides from degradation by nuclease. Cell studies showed a 20% sequence-specific inhibition of cell growth in MTT assay and revealed an LC50 of 103 nM in colonogenic studies. In conclusion, ethanol injection was able to provide suitable liposomes from the permanently charged DOTAP. Also the resulted liposomes were able to inhibit the growth of lung cancer cells.

The purpose of the present study was to investigate the effect of polyethylene glycol (PEG) molecular weights (6000, 12000 and 20000) as solid dispersion (SD) carriers on the dissolution behavior of simvastatin. SDs with various drug: carrier ratios were prepared by solvent method and evaluated for dissolution rate. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), infrared spectroscopy and solubility studies were also performed on the optimum SD formulation. Samples prepared with all three types of PEG showed improved drug dissolution compared to intact drug and corresponding physical mixtures. Meanwhile, the best result was obtained by PEG 12000 with drug: carrier ratio of 1:7 which showed a 3-fold increase in dissolution rate compared to the intact drug. Based on DSC and XRD, no crystalline change occurred during the sample preparation. Solubility studies revealed that increasing the PEG molecular weight resulted in higher phase solubility of drug. In addition, saturated solubility of the optimum SD was significantly higher than that of intact drug and the related physical mixture (24.83, 8.74 and 8.88 μg/mL, respectively) that could be due to the decreased particle size and aggregation. The results confirmed the influence of PEG molecular weight on drug dissolution rate from solid dispersion systems.

Vitamin E (α-tocopherol) is a natural antioxidant very useful for preventing the harmful effects of UV sun rays as skin aging and cancers. In this study, different MLV formulations were made using egg lecithin and varying molar ratios of α-tocopherol and/or cholesterol, and their encapsulation efficiencies were determined. The best liposomal product was incorporated into a carbomer 980 gel. The resulting preparation was then studied with regard to the rheology and release profile using r2 values and Korsmeyer-Peppas equation. The encapsulation efficiency was dramatically decreased when using α-tocopherol at molar ratios of 1:10 or more, which is suggested to be due to the defect in regular linear structure of the bilayer membrane. Addition of cholesterol to formulations caused a decrease in encapsulation efficiency directly related to its molar ratio, which is due to the condensation of the bilayer membrane as well as competition of cholesterol with α-tocopherol. The liposomal gel showed a yield value of 78.5 ± 1.8 Pa and a plastic viscosity of 27.35 ± 2.3 cp. The release showed a two-phase pattern with the zero-order model being the best fitted model for the first phase. However, the “n” and r2 values suggested a minor contribution of Higuchi model due to some diffusion of α-tocopherol from the outermost bilayers of the MLVs to the gel. The second phase showed a non-Fickian release indicating a more prominent role for diffusion. This combinational release profile provides a high initial concentration of α-tocopherol followed by a slow release throughout a 10 h period.

Atropine (AT) and oximes, alone or in combination, have been proven greatly valuable therapeutics in the treatment of organophosphates intoxications. An injectable mixture of AT and obidoxime (OB) was formulated for administration by automatic self-injector. The aqueous single dose solution contained 275 mg obidoxime chloride and 2.5 mg atropine sulfate per 1 ml (220 mg and 2 mg per 0.8 effective dose, respectively). The final solution was sterilized by filtration through a 0.22 µm pore size filter. This more concentrated solution allowed to use a smaller size and lighter weight cartridge. Quality control tests, including assay of the two major compounds were performed separately, using reversed-phase HPLC methods. Also, stability test was carried out according to ICH guideline for accelerated test. The obtained results showed that the proposed formulation is stable over a period of 2 years after preparation.

Etoposide, a widely used anticancer drug, exhibits low and variable oral bioavailability mainly because of being substrate for the efflux transporter, P-glycoprotein (P-gp). Therefore, the present study was aimed to investigate the effect of D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and PEG 400 as P-gp inhibitors on the intestinal absorption of etoposide. Everted sacs of rat small intestine were incubated in Krebs buffer solution which contained etoposide in the absence or presence of various concentrations of TPGS or PEG 400. The effect of verapamil as a known P-gp inhibitor on the absorption of drug was also studied.The absorptive transport of etoposide was significantly enhanced (p < 0.001) in the presence of verapamil (100 µg/mL) and TPGS (over the concentration range of 0.002-0.1 mg/mL), suggesting that the inhibition of P-gp located in the intestine may be involved in the enhancement of etoposide absorption. However, the addition of PEG 400 at various concentrations (0.05, 0.1 and 0.5% w/v) had no effect on the etoposide transport. No significant difference was found between the permeability values in the absence and presence of the maximum concentration of TPGS for two transport markers, lucifer yellow and imipramine, indicating that the enhancement in etoposide permeability in the presence of TPGS was not due to the compromise in tight junctions or membrane integrity of epithelial cells.The results of the study suggest that the use of TPGS as a safe excipient in etoposide formulations may enhance the oral bioavailability of etoposide and result in a predictable oral absorption.

Crystalline arrays of proteinaceous subunits forming surface layers (S-layers) are now recognized as one of the most common outermost cell envelope components of prokaryotic organisms. The surface layer protein of Lactobacillus acidophilus ATCC4356 is composed of a single species of protein of apparent molecular weight of 43-46 KDa. Considering the Lactobacillus acidophilus ATCC4356 having the S-layer is stable in harsh gastrointestinal (GI) conditions, a protective role against destructive GI factors which has been proposed for these nanostructures. It opens interesting perspectives in the using and development of this S-layer as a protective coat for oral administration of unstable drug nanocarriers. To achieve this goal, it is necessary to study the in-vitro stability of the S-layers in the simulated gastrointestinal fluids (SGIF). This study was planned to evaluate the in-vitro stability of the extracted S-layer protein of Lactobacillus acidophilus ATCC4356 in SGIF using it as a protective coat in oral drug delivery. Sodium dodecyl sulfate gel electrophoresis (SDS-PAGE) and circular dichroism (CD) spectroscopy were used to study the stability of the S-layer protein incubated in SGIF. Both the SDS-PAGE and CD spectra results showed that Lactobacillus acidophilus ATCC4356 S-layer protein is stable in simulated gastric fluid (SGF) with pH = 2 up to 5 min. It is stable in SGF pH = 3.2 and above it, with and without pepsin. It is also stable in all the simulated intestinal fluids. This S-layer is also stable in all of the simulated intestinal fluids.

The present study was designed to develop a simple, validated liquid chromatographic method for the analysis of azithromycin in bulk and pharmaceutical dosage forms using ultraviolet detector. The best stationary phase was determined as C18 column, 5 µm, 250 mm × 4.6 mm. Mobile phase was optimized to obtain a fast and selective separation of the drug. Flow rate was 1.5 mL/min, Wavelength was set at 210 nm and the volume of each injection was 500 µL. An isocratic methanol/buffer mobile phase at the ratio of 90:10 v/v gave the best separation and resolution. The proposed method was accurate, precise, sensitive, and linear over a wide range of concentration of azithromycin. The developed method has the advantage of using UV detector compared to the USP method in which electrochemical detector has been used. The validated method was successfully applied to the determination of azithromycin in bulk and pharmaceutical dosage forms

A rapid, sensitive and reproducible HPLC method using amperometric detector was developed and validated for the analysis of clarithromycin in human plasma. The separation was achieved on a monolithic silica column (MZ- C8 125×4.0 mm) using acetonitrile- methanol-potassium dihydrogen phosphate buffer (40:6:54,v/v), with pH of 7.5, as the mobile phase at a flow rate of 1.5 mL/min. The assay enables the measurement of clarithromycin for therapeutic drug monitoring with a minimum quantification limit of 20 ng/mL. The method involves simple, protein precipitation procedure and analytical recovery was complete. The calibration curve was linear over the concentration range of 0.1-6 µg/mL. The coefficients of variation for inter-day and intra-day assay were found to be less than 6%. This method was used in bioequivalency and pharmacokinetic studies of the test (generic) product 2 × 500 mg clarithromycin tablets, with respect to the reference product.

One of the problems encountered in CE separations of basic compounds is the adsorption of analytes onto the negatively charged capillary wall which could lead to poor repeatability of migration time and peak area. Additionally, separation of enantiomers of chiral of basic drugs is commonly carried out in low pH buffer which contributes to strong ionic interaction of the cationic drug ions with negatively charged chiral selectors. The two phenomena results in poor enantioseparations. To overcome the problems associated with chiral separations of basic drugs by CE, the effect of guanidine (GU) on the improvement of chiral separation of a model basic drug, fluoxetine (FLX), was investigated. In the present study, GU was used as a cationic additive to the running buffer containing a chiral selector, sulfated beta cyclodextrine. Better results obtained with GU as the buffer additive in enantioseparation of FLX.

Easily degradating and various isomeric forms of rapamycin (Sirolimus) face the determination of this compound to many challenges. In this study, we developed and validated the isocratic reversed phase high performance liquid chromatographic (RP-HPLC) method for rapamycin. Separation was performed on a C8 column (MZ, 15 × 4.6 mm, 5 µm particle size) using methanol:water (80:20 v/v) as the mobile phase with the flow rate of 1 mL/min. The column temperature was set at 57°C and the detection was carried out at the wavelength of 277 nm. The method was linear over a concentration range of 0.025-2 µg/mL. The coefficient of variation of intra- and inter-day, assessed at three concentration levels of 0.075, 0.3 and 0.900 µg/mL, was less than 2%. Limit of quantification (LOQ) was found 25 ng/mL. The method with high percent recovery and short retention time of rapamycin, was found to be simple, rapid and reproducible.

A high performance liquid chromatographic method was developed for determination of aflatoxin B1 (AFB1) in foods using a monolithic column with sample clean up on an immunoaffinity column. The method was validated for analysis of AFB1 in rice, bread, puffed corn snack, wheat flour and peanut samples. The average recoveries for AFB1 in different foods ranged from 94.4 to 102.5% with the coefficient of variation lower than 10% for all foods. Limit of detection was 0.01 ng/g. A survey of AFB1 was performed on 90 samples collected from Tehran retail market in June 2005. The results showed that none of the bread and wheat flour samples were contaminated with AFB1. The mean AFB1 levels in rice, puffed corn snack and peanut samples were 4.17, 0.11, and 1.97 ng/g, respectively. The level of contamination of 3 samples (one rice sample and two peanuts samples) to AFB1 was found to be higher than 5 ng/g. Although all food samples had mean concentration of AFB1 below the maximum tolerated level in Iran, the mean intake of AFB1 from rice was estimated 3.49 times higher than the guidance value of 1 ng AFB1/Kg body weight/day. Therefore, it is strongly recommended to monitor AFB1 in foods, especially in rice, in Iran. This is the first study on exposure assessment of Iranian population to AFB1.

Electrochemical oxidation of some selected catechol derivatives, using cyclic voltammetry, in the presence of different 2-aryl-1,3-indandiones as nucleophiles, resulted in electrochemical synthesis of new 1,3- indandione derivatives in an undivided cell in good yield and purity. A Michael addition mechanism was proposed for the formation of the analogs based on the reaction conditions which were provided in electrochemical cell. The in-vitro antiplatelet and anticoagulant activity of these compounds was evaluated, using arachidonic acid (AA) and adenosine diphosphate (ADP) as the platelet aggregation inducers. The results show that the incorporation of catechol ring in 1,3-indandione nucleus leads to the emergence of antiplatelet aggregation activity in these compounds. The compounds may exert their antiaggregation activity by interfering with the arachidonic acid pathway.

Benzodiazepines are useful drugs for treatment of sleep disorders, anxiety, seizure cases and skeletal muscle cramps. Some derivatives of 2-(2-Phenoxy) phenyl-1, 3, 4-oxadiazole were synthesized as benzodiazepine receptor agonists. Conformational analysis and superimposition of energy minima conformers of the compounds on estazolam, a known benzodiazepine agonist, reveal that the main proposed benzodiazepine pharmacophores were well matched. Anticonvulsant activity of the synthesized compounds, determined by pentylenetetrazole-induced lethal convulsion test, showed that the introduction of an amino substituent in position 5 of 1,3,4- oxadiazole ring generates compound 9 which has a respectable effect. The results are in agreement with SAR of benzodiazepine receptor ligands since the elimination of electronegative substituent in position 2 of phenoxy ring or position 4 of phenyl ring reduces the anticonvulsant activity.

Four halotolerant fungal isolates originating from the saltwater Lake Urmia in Iran were selected during a screening program for salt resistance and α-amylase activity. The isolates were identified based on sequencing the ITS region and a part of the β-tubulin gene, as Penicillium chrysogenum (isolate U1; CBS 132820), Fusarium incarnatum (isolate U2; CBS 132821), and Penicillium polonicum (isolate U3; CBS 132822, and isolate U4; CBS 132823). The growth of these isolates was determined by measuring the colony diameter and mycelia dry weight in Sabouraud dextrose agar and yeast nitrogen base medium supplemented with NaCl, KCl, and LiCl. Isolate U4 showed a growth up in 15% NaCl and U1 was the only isolate that could grow in 20% KCl. None of the strains grew in a media containing LiCl. The salt supplemented medium did not increase the size of colony diameter in all isolates (p > 0.05). The ability of the selected isolates for amylase production was quantitatively tested and showed that P. polonicum isolate U4 was the most potent producer of amylase with a yield of 260.9 U/L after 60 h, whereas P. polonicum isolate U3 was the lowest one with a production level of 97.9 U/L after 48 h. P. polonicum isolate U4 could be a suitable candidate for production of amylase on an industrial scale after optimization.

Arsenic exposure mainly through food and water has been shown to be associated with increased incidence of numerous cancers and non-cancer harmful health. It is also used in cancer chemotherapy and treatment of several cancer types due to its apoptogenic effects in the various cancer and normal cell lines. We have already reported that liver is the storage site and important target organ in As (III) toxicity and recently, it has been suggested that hepatic toxicity of arsenic could be resulted from impairment of the liver mitochondria. In this study, interaction of As (III) with freshly isolated rat mitochondria was investigated. We determined different mitochondrial toxicity factors as well as mitochondrial sources of ROS formation using specific substrates and inhibitors following addition of As (III) to the mitochondria. Our results showed that arsenic (III) increased mitochondrial ROS formation, lipid peroxidation and mitochondrial membrane potential collapse, cytochrome c release and mitochondrial swelling in a concentration dependent manner. Addition of As (III) in to the isolated mitochondria, inhibited complexes I and II leading to disruption of mitochondrial electron transfer chain, decreased mitochondrial ATP content and ROS formation.

In this research, the survival of probiotic microorganisms in yogurts stored at room temperature (cold chain interruption conditions) was studied. Milk inoculated with yogurt bacteria (mixed culture of Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus) and a single probiotic culture (L. acidophilus LA-5 or Bifidobacterium lactis Bb-12 or L. rhamnosus HN001 or L. paracasei Lpc-37) were incubated till pH of 4.5 was reached. Probiotic yogurts were stored at two different temperatures including cold (control) and room temperatures (5 and 20°C, respectively). Changes in pH decrease, titratable acidity increase and redox potential increase as well as the viability of probiotics per 6 h intervals during an assumptive interrupted cold storage (24 h) were monitored. The survival of probiotics was strongly dependent on the storage temperature and remarkable viability loss occurred in room temperature compared to refrigerated storage. In addition, the survivability was dependent on probiotic strain. Among our experimental strains, B. lactis Bb-12 showed the less resistance to be stored at 20°C (24 h) and referring to the recommended minimum numbers of 107 cfu mL-1, L. rhamnosus HN001 was the most suitable probiotic strain to be used in probiotic yogurts especially in countries having high possibility of cold chain interruption during storage.

Temporary paralysis is a rare manifestation of envenoming following the yellow Iranian scorpion, Odontobuthus doriae (O. doriae). Thus, to elucidate the underlying mechanism, we investigated the neurotoxic effect of venom in the sciatic nerve, the possible mechanism in a mice model. The neurotoxicity and temperature effects in the venom-induced neurotoxicity were examined using the mouse sciatic nerve and mouse phrenic nerve-hemidiaphragm (MHD) preparations. O. doriae venom (1 µg/mL) caused changes in the perineural waveform associated with nerve terminal action potentials. Venom affected on both negative and positive components of the waveform which is known as a compound action potential. The time-response relationship of venom-induced depression of resting membrane potential (RMP) was significant (p < 0.05). No significant difference in augmentation was seen in room temperature in comparison with 37°C. In conclusion, although there was no evidence that the venom had any specific curarizing action at the neuromuscular junction, the results suggest that the venom exerts its neuromuscular transmission on the sciatic nerve through potassium and sodium ionic-currents. Furthermore, the influence of temperature on neurotoxicity was ineffective on blockade of the neuromuscular transmission in-vitro.

Chalcone (1,3-diarylprop-2-en-1-one) derivatives have been introduced as selective cyclooxygenase-2 inhibitors. In the present study, anti-nociceptive and anti-inflammatory effects of eight novel compounds were evaluated in male mice and Wistar rats by using the writhing and formalin-induced paw edema tests respectively. The activities of the compounds were compared with celecoxib as a reference drug. Then, novel compounds were divided into two regioisomeric groups based on the position of the methylsulfonyl substitution. Compounds with substituents such as: 1) H, 2) Me, 3) F and 4) Cl at para position of the phenyl ring of (E)-3-(4-Methanesulfonylphenyl)-1-phenylprop-2-en-1-one were selected in the first group. The regioisomer compounds with 5) H, 6) Me, 7) F and 8) OMe substitutions at C-4 of phenyl ring of (E)-1-(4-Methanesulfonylphenyl)-3-phenylprop-2-en-1-one were chosen as second group. All compounds showed dose-dependent anti-nociceptive activity in writhing test. Interestingly, the potency of anti-nociceptive effect of compounds 1, 2, 5 and 6 were significantly higher than celecoxib. The regioisomeric compounds 1 and 5 with high anti-nociceptive effects, showed a significant dose-dependent anti-inflammatory activity in the paw edema test as well. The results showed that compounds with no substituent or small size substituents at para position of the phenyl ring are the most potent compound in writhing test. Our results revealed that the introduction of a bulky group such as methoxy or chlorine at the vicinal aromatic chain of the derivatives decreases the anti-inflammatory/anti-nociceptive effects. The comparison of estimated ED50 of each pair of the regioisomeric compounds indicates that the relative position of SO2Me to carbonyl moiety did not affect the potency.

Drug Utilization Evaluation (DUE) studies are designed to assess drug usage appropriateness. We aim to evaluate the drug utilization of intravenous ciprofloxacin and imipenem, two of the broad spectrum antibiotics that consume a significant proportion of our hospitals’ outlay, in different wards of a teaching hospital in Zabol. During a 5 months period (December 2010 to May 2011), 263 patients who received imipenem or intravenous ciprofloxacin were assigned to this study. Retrospective review of patient’s records was carried out. Data were converted to Defined Daily Dose (DDD) and the ratio of prescribed daily dose per DDD was calculated. Among these records, 100 patients received either imipenem or ciprofloxacin. The ratio of prescribed daily dose to DDD was 1.5 for both antibiotics. Almost all patients received empiric therapy in both groups. Only 13 patients (26%) in ciprofloxacin group and 4 patients (8%) in imipenem group received their antibiotics consistent with American Hospital Formulary System (AHFS) mentioned indication. Baseline Blood Urea Nitrogen (BUN) and serum Creatinine were ordered for only 37 patients (74%) in both groups with 15 abnormal results but dose adjustment performed just in one case with decreased renal function. In conclusion, the majority of courses with both drugs were empirically selected and continued and required lab tests for drug monitoring and dose adjustments were not performed in most cases. Educational interventions, developing a local formulary and a strict antibiotic prescribing policy for example by prior approval by an infectious disease consultant can help significantly to overcome these problems.

To study the resistance to standard dosage of clopidogrel among Iranian patients following percutaneous coronary intervention measured by platelet aggregation test.Patients undergoing percutaneous coronary intervention in Imam Hussein Medical center, Tehran, Iran, who were under treatment with aspirin, but had no history of clopidogrel usage, entered the study. Patients received standard dosage of clopidogrel (Plavix®, Sanofi, France, 600 mg loading dose and 75 mg/day afterward). Platelet aggregation was measured using light transmission aggregometer. The response to the drug was categorized as complete resistance (platelet aggregation decreased less than 10%), intermediate resistance (platelet aggregation decreased between 10 to 30%) and complete response (platelet aggregation decreased to 30% or more). All patients were evaluated for major adverse cardio vascular events one month after the angioplasty based on MACE criteria by phone contact.Thirty-one patients with a mean age of 59 ± 13 entered the study. Sixty-five percent of patients showed complete response to clopidogrel (95% CI: 45% to 81%), 22% showed intermediate resistance (95% CI: 10-41%) and 13% showed complete resistance (95% CI: 4-30%). One month after the angioplasty, no major adverse cardiovascular event was recorded.Based on our findings, it seems that there is no major difference between Iranian population and other studies regarding the resistance to clopidogrel. Due to the limited number of participants in our study, further investigations with higher number of patients are recommended to more precisely calculate the percentage of resistance among Iranian patients.

Cancer patients are more susceptible to adverse drug-drug interactions (DDIs) due to receiving multiple medications especially chemotherapy medications, hormonal agents and supportive care drugs. The aim of this study is to describe the prevalence of potential DDIs and to identify risk factors for these potential interactions in hospitalized cancer patients in a developing country.A cross-sectional study conducted by reviewing charts of 224 consecutive in hospitalized patients in hematology-oncology ward of a teaching hospital in Tehran, during a 12 month period from July 2009 to July 2010. “Drug Interaction Facts 2008, 2009: The Authority on Drug Interactions” was used for screening the potential drug-drug interactions. Potential interactions were classified by levels of severity and documentation.The median age of patients was 50 years, the length of hospital stay for patient was 5 days and the number of drugs per patient was 8 drugs. Two hundred and twenty-eight potential interactions were detected. Nearly 14% of the interactions were major and 60% were moderate. Approximately 9% and 10% potential interactions were graded as established and probable. In multivariate analysis, being older than 61 years old, suffering from hematologic cancer, source of cancer in different specific organs (esophagus, testis and cervices more than other sources), and number of ordered drugs for patients were independent predictors of having at least one potential DDI in hospital order. Suffering from hematologic cancer, source of cancer in different organs, length of hospital stay and number of ordered drugs for patients were independent predictors for number of interactions per patients.Having a DDI seems to be more likely to occur in patients older than 61 years old. Hematologic cancers, having more medications in physician’s order, longer length of hospital stay, esophageal cancer, testicular cancer and cervical cancer have related to having a DDI and also having more number of interactions.

The aim of this study was to evaluate the satisfaction rate of hospital managerial/clinical teams (HMCTs) including principles (chief executives), managers, supervisor pharmacists and head nurses from services presented by private sectors directing 10 pharmacy departments in hospitals affiliated to Shahid Beheshti University of Medical Sciences.This study is an observational and descriptive study in which a questionnaire containing 16 questions evaluating the satisfaction of the HMCTs from private sectors, and questions about demography of the responders was used for data collection. Collected data was applied to assign a satisfaction score (maximum 64) for each respondent. SPSS 17.0 and Microsoft Office Excel 2007 were used for statistical description and analysis of these information (where applicable).Overall, 97 people in charge of the hospitals (HMCTs) entered the study. The average satisfaction score was 26.38 ± 6.81 with the lowest satisfaction rate observed in Mofid children specialty hospital (19.5%) and the highest rate obtained for Imam Hussein (p.b.u.h) general hospital (65.3%). Generally, 59% of the HMCTs believed that the function of the private sector in the pharmacy of hospitals is satisfactory.Assuming that the satisfaction scores under 75% of the total obtainable score (i.e. 48 out of 64) could not be considered as an indicator of desired pharmacy services, our results revealed that the status of the services offered by private sectors are far behind the desired satisfactory level.

High-dose chemotherapy and autologous stem cell transplantation (SCT) have become an effective care for many patients with hematological malignancies. Harvesting the stem cells is one the most important parts of SCT. The two most commonly used mobilization regimens are the use of granulocyte colony-stimulating factor (G-CSF) or G-CSF plus chemotherapy. However, about 10-30% of patients are unable to collect enough cells to support HSCT due to previous chemotherapies, radiation, marrow involvement or fibrosis. In multiple myeloma patients, it is hard to collect enough stem cells when the bone marrow is extensively involved. Plerixafor has emerged as a novel mobilizing agent and its efficacy has been shown in two phase III studies. Considering the importance of autologous SCT in patients with multiple myeloma, we report the first successful Iranian experience at Tehran Taleghani bone marrow transplantation center using plerixafor to mobilize stem cells in a patient with refractory multiple myeloma with extensive bone marrow involvement who failed mobilization with G-CSF.

Agility is the fundamental characteristic of a supply chain needed for survival in turbulent markets, where environmental forces create additional uncertainty resulting in higher risk in the supply chain management. In addition, agility helps providing the right product, at the right time to the consumer. The main goal of this research is therefore to promote supplier selection in pharmaceutical industry according to the formative basic factors. Moreover, this paper can configure its supply network to achieve the agile supply chain. The present article analyzes the supply part of supply chain based on SCOR model, used to assess agile supply chains by highlighting their specific characteristics and applicability in providing the active pharmaceutical ingredient (API). This methodology provides an analytical modeling; the model enables potential suppliers to be assessed against the multiple criteria using both quantitative and qualitative measures. In addition, for making priority of critical factors, TOPSIS algorithm has been used as a common technique of MADM model. Finally, several factors such as delivery speed, planning and reorder segmentation, trust development and material quantity adjustment are identified and prioritized as critical factors for being agile in supply of API.

To be sure, all the industries try to be involved in globalization with a constant trend to find out ways to increase productivity across different functions within an organization to maintain competitive advantage world. Pharmaceutical industries are not exceptional and further are based on fragmentation. So these kind of companies need to cope with several barriers such as silo mentality that may affect efficiency of their business activity. Due to eliminate a part of resources such as raw materials, new molecule developed, financial and human resources and so on, companies can gradually loss their competitive potentials in the market and increase their expenses.Furthermore, to avoid any business disturbances in financially connected companies due to silo effect, they should arrange their management to integrated organization form. Otherwise, actions taken by one business member of the chain can influence the profitability of all the other members in the chain. That is why recently supply chain has generated much interest in many business units.In this paper, it has been tried to investigate the different aspects of silo effect which can affect integrate supply chain.Finally, a fluent communication, high level of information exchange, fragmentation management, cross-functional control in a supply chain management format are needed to reduce or control silo effect within entire chain of the holding company by Supply chain management.