فهرست مطالب
Pharmaceutical Sciences
Volume:27 Issue: 3, Sep 2021
- تاریخ انتشار: 1400/06/03
- تعداد عناوین: 15
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Pages 302-312
Trisomy 21 is the most prevalent aneuploidy disorder among live-born children worldwide. Itresults from the presence of an extra copy of chromosome 21 which leads to a wide spectrum ofpathophysiological abnormalities and intellectual disabilities. Nevertheless human chromosome21 (HSA21) possess protein non-coding regions where HAS-21 derived-microRNA genes aretranscribed from. In turn, these HSA21-derived miRNAs curb protein translation of severalgenes which are essential to meet memory and cognitive abilities. From the genetics andmolecular biology standpoints, dissecting the mechanistic relationship between DS pathology/symptoms and five chromosome 21-encoded miRNAs including miR-99a, let-7c, miR-125b-2,miR-155 and miR-802 seems pivotal for unraveling novel therapeutic targets. Recently,several studies have successfully carried out small molecule inhibition of miRNAs function,maturation, and biogenesis. One might assume in the case of DS trisomy, the pharmacologicalinhibition of these five overexpressed miRNAs might open new avenues for amelioration of theDS symptoms and complications. In this review, we primarily elucidated the role of HSA21-encoded miRNAs in the DS pathology which in turn introduced and addressed importanttherapeutic targets. Moreover, we reviewed relevant pharmaceutical efforts that based theirgoals on inhibition of these pathological miRNAs at their different biogenesis steps. We havealso discussed the challenges that undermine and question the reliability of miRNAs as noneinvasivebiomarkers in prenatal diagnosis.
Keywords: Down syndrome, Parthenogenesis, Trisomy 21, microRNAs, Prenatal diagnostic -
Pages 313-325Background
Alzheimer’s disease is the main form of dementia, which affects more than46 million people every year. In the pathogenesis of Alzheimer’s disease, a significant roleplayed mitochondrial dysfunction, which is a promising pharmacotherapeutic target ofneuroprotective therapy. In this regard, this study aimed to evaluate the effect of the 4-hydroxy-3,5-ditretbutyl cinnamic acid on changes of mitochondrial function in experimental Alzheimer’sdisease induced by Aβ injection in rats.
MethodsAlzheimer’s disease was modeled on Wistar rats by injecting a fragment of β-amyloid(Aß 1-42) into the CA1 part of the hippocampus. The test-compound (4-hydroxy-3,5-ditretbutylcinnamic acid, 100 mg/kg, per os) and the reference drugs (resveratrol, 20 mg/kg, per os andEGB671, 100 mg/kg, per os) were administered for 60 days after surgery. The restoration of amemorable trace in animals was evaluated in the Morris water maze test. The concentrationof β -amyloid, Tau-protein, and changes in parameters characterizing mitochondrial function(cellular respiration, concentration of mitochondrial ROS, activity of apoptosis reactions(caspase-3 and apoptosis induced factor) were also determined.
ResultsThis study showed that the administration of 4-hydroxy-3,5-ditretbutyl cinnamic acidat a dose of 100 mg/kg (per os) in rats with reproduced Alzheimer’s disease contributed to thenormalization of mitochondrial respiratory function. It was expressed in the normalizationof aerobic metabolism, increased activity of respiratory complexes and stabilization ofmitochondrial membrane potential. Also, when animals were treated with 4-hydroxy-3,5-ditretbutyl cinnamic acid, there was a decrease in the concentration of intracellular calcium(by 39.7% (p<0.05)), the intensity of apoptosis reactions, and an increase of the latent time ofthe mitochondrial permeability transition pore opening (by 3.8 times (p<0.05)), and decreasesH2O2 concentration (by 21.2% (p<0.05)).
ConclusionIn the course of this study, it was found that 4-hydroxy-3,5-ditretbutyl cinnamicacid exceeds the value of neuroprotective action in compared to the reference agents –resveratrol (20 mg/kg) and Ginkgo biloba extract (EGB671, 100 mg/kg).
Keywords: Alzheimer's disease, Cinnamic acid derivatives, Mitochondrial dysfunction, Neuroprotection -
Pages 326-338Background
4-Aminoquinoline derivatives possess various potential biological properties.The introduction of additional piperazine heterocyclic pharmacophoric moiety tends to haveprofound impact in increasing the activity. The present work was undertaken to investigate thein-vitro and in-vivo anti-inflammatory activity as well as the peripheral and central analgesicactivities of compound 1-(4-(7-chloroquinoline-4-yl)piperazin-1-yl)-2-(4-phenylpiperazin-1-yl)ethanone (5) in experimental models.
MethodsThe percentage inhibition of the lipopolysaccharide induced NO release of 7-chloro-4-(piperazin-1-yl)quinoline derivatives 1-9 was determined in RAW 264.7 murine macrophagemodel. Western blot analysis was performed to evaluate the effect of compound 5 on proteinexpression of inducible nitric oxide synthase (iNOS). Gene expression of inflammatory markerswas evaluated using real-time polymerase chain reaction. The peripheral and central analgesicactivities of compound 5 were evaluated in mice using writhing and hot-plate tests, respectively.Anti-inflammatory activity was assessed using carrageenan-induced paw edema assay in miceand serum NO and COX-2 levels were measured.
ResultsCompound 5 demonstrated the highest NO inhibitory activity that was accompaniedby inhibition of iNOS protein expression and decreased gene expression levels of inflammatorymarkers. It revealed a potential peripheral analgesic effect through inhibition of abdominalwrithing in mice treated with doses of 15 and 30 mg/kg and its effect was comparable to diclofenacsodium. Compound 5 possessed an analgesic activity starting from 15 min post administrationand reached its peak at 45 min which was significantly higher than that of tramadol hydrochloridesuggesting its potential as central analgesic agent. It also showed percentage of inhibition ofedema of 34, 50 and 64% at 1, 2, and 3 h respectively, post carrageenan challenge together with asignificant decrease in serum NO and COX-2 levels.
ConclusionThe remarkable anti-inflammatory and analgesic activities of compound 5 couldbe attributed to the advantageous introduction of the heterocyclic 7-chloro-4-(piperazin1-yl)quinoline scaffold incorporated with N-phenylpiperzine functional groups linked together withthe ethanone pharmacophoric chain.
Keywords: Nitric oxide, Anti-inflammatory, Analgesic, 7-chloro-4-(piperazin-1-yl)quinolines -
Pages 339-344Background
Antioxidant drugs may be useful in preventing morphine-induced dependency bysuppressing oxidative stress. Vitamin E which has many essential roles in the body is a powerfulantioxidant. On the other hand, selenium is an essential trace element that plays a strong rolein various biochemical pathways. The aim of this study was to investigate the effects of sodiumselenite and vitamin E on morphine-induced dependency in mice.
MethodsNinety male mice, weighing 20 to 30 g, were randomly divided into 10 groups and weretreated as follows: a) saline and b) morphine groups were pretreated (for 2 days) with normalsaline (10 ml.kg-1.day-1, ip) then daily doses of normal saline (10 ml.kg-1.day-1, ip) and morphine(50 mg.kg-1.day-1) were added to the injections for the following 4 days, respectively. c, d, e)sodium selenite, f, g, h) vitamin E, i) vitamin E solvent (almond oil) and j) co-administrationgroups were pretreated (for 2 days) with sodium selenite (0.25, 0.5, 1 mg.kg-1.day-1, ip), vitaminE (20, 40, 60 IU.kg-1.day-1, ip), vitamin E solvent (10 ml.kg-1.day-1, ip) and combination of thedrugs respectively, then morphine doses (50 mg.kg-1.day-1, ip) were added to the injections forthe following 4 days. Withdrawal symptoms were evaluated after injecting naloxone (4 mg/kg/day). Biochemical evaluations were also performed.
ResultsThe results showed that co-administration of sodium selenite and vitamin E (at lowdoses) significantly reduced morphine dependency (p < 0.05).
ConclusionThe synergistic effect of sodium selenite and vitamin E can be a suitable andefficient approach to reduce dependency.
Keywords: Morphine, Sodium selenite, Vitamin E, Mice, Withdrawal syndrome -
Pages 345-352Background
Cancer is a major cause of death all over the globe. Controlling cell division byinhibition of mitosis is the most successful clinical strategy for cancer treatment. The developmentof novel anticancer agents is the most important area in medicinal chemistry and drug discoveryresearch. Thiazolidine is the multifunctional nucleus which shows a number of pharmacologicalactivities like anticancer, anti-inflammatory, antioxidant, antibacterial, antifungal, antidiabetic,antihyperlipidemic and antiarthritic.
MethodsIn a present study series of 2-substituted-3-(1H-benzimidazole-2-yl)-thiazolidin-4-ones were designed, synthesized by the microwave-assisted system, and characterized bymelting point, IR, 1H NMR, and mass spectroscopy. All the newly synthesized compoundswere examined for their in vitro anticancer activity against breast cancer cell line MCF-7 bySulforhodamine B (SRB) assay.
ResultsThe compounds AB-12 (GI50: 28.5 μg/ml) and AB-6 (GI50: 50.7 μg/ml) exhibitedsignificant cell growth inhibitory activity.
ConclusionThese results indicate that compound AB-12 and AB-6 as related polo-like kinase1inhibitors compounds could be lead compounds for further development of anticanceragents.
Keywords: Anticancer activity, MCF-7 cell line, Molecular Modelling, Polo like kinase 1 inhibitors, Thiazolidine-4-one, Synthesis -
Pages 353-365Background
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world. The widespread use of NSAIDs is associated with a number of serious side effects and complications observed for both selective and non-selective COX inhibitors. Therefore, the search for new COX inhibitors, which along with their effectiveness will have minimal side effects, is a very important and urgent task.
MethodsThis work studied the synthesis of new 1,4,5,6-tetrahydropyrimidine-2-carboxamides based on the reaction of 2-morpholin-4-yl-N-(het)aryl-2-thioxoacetamides with 1,3-diaminopropane. All obtained compounds were tested for anti-inflammatory activity in vitro and in silico conditions. All synthesized 1,4,5,6-tetrahydropyrimidine-2-carboxamides were tested for influence on the course of the exudative phase of the inflammatory process based on the carrageenan model of paw edema of laboratory nonlinear heterosexual white rats weighing 220-250 g, using Diclofenac as a reference. Optimization of the geometry of the studied structures and molecular docking was carried out using the ArgusLab 4.0.1 software package.
ResultsThe target products were obtained with yields of 71-98% and easily isolated from the reaction mixture. The best anti-inflammatory activity was found in N-(4-chlorophenyl)-1,4,5,6-tetrahydropyrimidine-2-carboxamide and in N-[4-chloro-3-(trifluoromethyl)phenyl]-1,4,5,6-tetrahydropyrimidine-2-carboxamide, suppression of the inflammatory response was 46.7 and 46.4%, respectively. The results of molecular docking with COX-1 and COX-2 enzymes were in good agreement with the experimental data, R2 ˃ 0.92 and R2 ˃ 0.83, respectively.
ConclusionThe compounds under study were shown to be promising as potential anti-inflammatory agents.
Keywords: Tetrahydropyrimidine, COX-1, COX-2, Antiinflammatory activity, SAR analysis, Molecular docking -
Pages 366-377Background
Physicochemical properties play important role in fundamental issues likeabsorption and distribution of pharmaceuticals to the target tissue. This is particularly importantfor drugs acting in central nervous system (CNS). In this study, physicochemical properties ofpreviously synthesized thiazole-pyridinium derivatives with anti-acetylcholinesterase activityand possible anti-Alzheimer effect were studied.
MethodsPartition coefficient (n-octanol/water) and chromatographic Rf values for the studiedcompounds were determined using shake flask and high performance thin layer chromatography(HPTLC) methods, respectively. Different druglikeness properties of the compounds were alsocalculated using available software and web-servers.
ResultsThe experimentally determined logarithm of partition coefficients (log P) for thestudied compounds were in the range of -1.00 to -0.38. The Rf values for the studied compoundsunder the applied chromatographic condition ranged between 0.38 to 0.58. Moreover, calculatedphysicochemical properties, and druglikeness scores of the studied thiazole-pyridiniumderivatives and matching piperidine analogues were predicted. Furthermore, some ADMETfeatures of studied compounds like toxicity and metabolism by CYP450 (2C9, 2D6, 3A4, 1A2and 2C19) enzymes were predicted.
ConclusionThe ranges of experimental and calculated LogP values for the studied thiazolepyridinumswere close. However, the determined Rf values showed relatively better correlationto the predicted LogP values indicating the suitability of used chromatographic method forcomparing the lipophilicity of the positively charged pyridinium derivatives. The studiedcompounds were predicted to pass GI membrane and reach the CNS where they can exerttheir effects. In silico studies indicate that the piperidine counterparts of the studied thiazolepyridiniumsmay represent anti-Alzheimer agents with improved druglikeness properties.
Keywords: Physicochemical property, Partition coefficient, High performance thin layer chromatography, Druglikeness, Thiazole-pyridinium -
Pages 378-384Background
Different Salvia species have demonstrated anti-proliferative effects on various cancer cells. Owing to the poor literature on the anti-proliferative effects of Salvia species on gastric cancer cells, present study was conducted to determine the anticancer effects of a local Iranian Salvia, Salvia chorassanica, on two different gastric cell lines.
MethodsRoot, stem and leaf extract of Salvia chorassanica were prepared through maceration method and were then used to treat the AGS and MKN-45 cell lines in different concentrations. MTT assay was employed to determine the toxicity of all the types of extracts on the two studied cell lines. The expression of Bax, Bcl-2, Caspase3, MMP2 and MMP9 genes were determined through reverse transcription Real time PCR (RT-PCR).
ResultsBunge and shoot extracts demonstrated toxicity in both cell lines which were more considerable in AGS cells treated with root extract. In contrary to AGS cells, Caspase3 gene was up-regulated in all types of treatment while the MMP2 and MMP9 genes were down-regulated (p-value<0.001). Except of the MKN-45 cells treated with leaf extract, Bax/Bcl-2 expression ratio was decreased in the treatment with all types of Salvia chorassanica extracts (p-value<0.001).
ConclusionRemarkable low IC50 concentration of root extract in MKN-45 cell line is indicating the significant cytotoxicity of Salvia chorassanica against gastric cancer cells. Moreover, gene expression analysis in MKN-45 needs further confirmation on the potential anti-metastatic roles of leaf and root extracts in higher grades of gastric cancer.
Keywords: Cytotoxicity, Gene expression, Salvia chorassanica, Tumor cell lines -
Pages 385-392Background
Childhood acute lymphoblastic leukemia (ALL) explains 26% of pediatricmalignancies and is one of the leading causes of disease-related deaths in children. A novelmolecular class of non-coding genes, long non-coding RNAs (lncRNAs) having over 200nucleotides, have been defined as regulators of different cellular processes including pluripotency,oncogenesis, and transcription. It has been demonstrated that lncRNA transcription profilescan distinguish pre B-cell subtype of ALL accurately and act as early diagnostic and prognosticbiomarkers. Hence, the aim of this pilot study was the prior evaluation of expression profileof several lncRNA candidates including RP11-68I18.10, RP11-624C23.1, RP11-446E9, RP11-137H2.4, and RP11-203E8 in patients with ALL.
MethodsIn this study, 80 blood samples were obtained from patients, definitely diagnosed bypathologists with ALL, and from healthy subjects. Total RNA was extracted from blood samples,and cDNA was synthesized. Real-time PCR was applied to determine the expression of lncRNAs.A P-value of 0.010 was considered statistically significant.
ResultsOur findings revealed that the expression levels of lncRNAs RP11-624C23.1, RP11-446E9, RP11-137H2.4, RP11-68I18.10, and RP11-203E8 were significantly decreased in ALLsamples compared to those of healthy samples (P<0.0001, P =0.0616, P =0.0292, P<0.0001, andP = 0.0007). Moreover, the relationship between these five lncRNA expression changes and theimmunophenotype in ALL patients was not significant.
ConclusionThe dysregulation of lncRNAs in ALL samples could provide a novel and interestingpossibility for early diagnosis and prognosis, as well as mastering the treatment of ALL.
Keywords: Long non-coding RNA, Acute lymphoblastic leukemia, Oncogenesis, Immune-phenotype -
Pages 393-398Background
DNA methyltransferase (DNMT) enzymes, encoded by DNMT1, DNMT3A andDNMT3B genes, play a major role in the development of cancers through aberrant promotermethylation. Due to little information about the biological and clinical significance of expressionchanges of these genes in Laryngeal Squamous Cell carcinoma (LSCC), the current study wasdesigned to evaluate the contribution of DNMTs expression as potential diagnostic biomarkersin progression of LSCC.
MethodsDNMT1, DNMT3A and DNMT3B expressions in tumoral and normal tissues fromthirty-three LSCC patients were evaluated by relative comparative real-time PCR, prior toany therapeutic intervention. Relationship between genes expression and clinicopathologicalfeatures were also analyzed.
ResultsThe mRNA expression levels of all three DNMTs (DNMT1, DNMT3A and DNMT3B)were significantly elevated in LSCC tumor specimens compared to that of non-tumor tissues(P<0.0001, P=0.011 and P<0.0001, respectively). The expression of DNMT1 and DNMT3Bwas strongly associated with histopathological tumor grade. Moreover, the mRNA expressionlevels of DNMT3A were significantly correlated with laryngopharyngeal reflux. No significantrelationships existed with other clinicopathological parameters.
ConclusionData showed that the expression levels of DNMT1, DNMT3A and DNMT3Bmarkedly increased in LSCC tissues. DNMT1 and DNMT3B were mainly overexpressed in highgrade LSCC tumors, therefore, they may have a role in LSCC progression. It seems that thesegenes may serve as diagnostic biomarkers in development of LSCC.
Keywords: Laryngeal squamous cell carcinoma, DNA methyltransferase, Expressional analysis, Histopathological grade, Biomarker -
Pages 399-406Background
Excipients are used in the formulation of pharmaceutical dosage forms, but mayinteract with active pharmaceutical ingredients (APIs). Some of these interactions could alterthe physicochemical properties of the APIs which can affect the therapeutic efficacy and safety.Acarbose is an anti-diabetic drug used in this study as an API to investigate its compatibility withcommon excipients in order to development of pharmaceutical controlled release formulations.
MethodsFor this purpose, 15 different excipients were selected. Binary mixtures of drug witheach of the excipients (1:1 mass ratio) were prepared. Mixtures were analyzed immediately aftermixing and also after incubation at stress conditions (adding 20% water and incubated at 40°Cfor 2 months). The thermal analytical investigation like differential scanning calorimetry (DSC),Fourier transform infra-red spectroscopy (FTIR) and high-performance liquid chromatography(HPLC) were employed for physicochemical evaluations of the possible incompatibility.Photodiode-array (PDA) and mass studies were performed to ensure the peak purity of theHPLC peaks of API in stressed samples.
ResultsIncompatible excipients with acarbose were determined as EC (ethyl cellulose),Carbopol 934, Hydroxypropyl cellulose, PEG2000 (Polyethylene Glycol 2000), Mg Stearate, NaAlginate and Poloxamer.
ConclusionResults of this study would be used for the development of controlled releaseformulation of acarbose. It is recommended to avoid the use of incompatible excipients.
Keywords: Acarbose, Compatibility, Controlled release, Excipient, Preformulation -
Pages 407-417Background
Glucocorticoids are employed for their anti-inflammatory effects in treatingglioma, whose cells are known to overexpress the folate receptors. Some glucocorticoids haveshown inhibitory effects, but the efficacy of prednisolone when delivered via folate receptormediateduptake, has not been attempted. The study aimed to assess the efficacy of targeteddelivery of prednisolone on glioma cell lines like C6 and U87 via the folate receptors.
MethodsTargeted delivery of prednisolone was achieved by initially conjugating folic acid (FA)to the di-block copolymer of polylactic acid (PLA) – polyethylene glycol (PEG). This moietycarrying di-block copolymer was incorporated on the surface of the drug-loaded poly lactic-coglycolicacid (PLGA) nanoparticle (NP) by employing the Interfacial Activity Assisted SurfaceFunctionalization (IAASF) technique. The NPs were evaluated for size, zeta potential, and drugloading. It was characterized using particle size analyser, SEM, 1H-NMR, and XRD. cell uptake,cytotoxicity, and anti-inflammatory activities were studied for various formulations.
ResultsThe cytotoxicity assay indicated a high cell growth inhibitory effect of drug encapsulatedNPs with FA moiety as compared to free drug and NPs without the moiety for an incubationperiod of three, five, and six days. The growth-inhibitory effect of the free drug was short-lived,whereas FA functionalized NPs showed higher uptake and sustained inhibitory effect, and werealso able to significantly control the release of pro-inflammatory cytokines like tumour necrosisfactor-alpha (TNF-α) and nitric oxide (NO).
ConclusionUptake, attenuation of pro-inflammatory signals, and the inhibitory effect ofprednisolone on the cells were more effective when targeted with the FA moiety on the surfaceof NPs as compared to free drug and NPs without the moiety.
Keywords: Folate receptor, Folic acid, Glioma, PLGA nanoparticle, Prednisolone, Receptor mediated uptake -
Pages 418-432Background
The clinical outcome of anti-HIV therapy is poor due to the inherent fallouts ofanti-HIV therapy. It is further worsened due to the presence of viral reservoirs in immune cellslike the macrophages. An ideal anti-HIV therapy must reach, deliver the drug and exert itsaction inside macrophages. To address this, we developed novel cationic nanostructured lipidcarriers of efavirenz (cationic EFV-NLC).
MethodsThe developed cationic EFV NLCs were evaluated for particle size, zeta potential,encapsulation efficiency, in-vitro drug release, DSC, XRD, TEM, cytotoxicity, cellular uptakestudies and anti-HIV efficacy in a monocyte-derived macrophage cell line (THP-1).
ResultsCationic EFV-NLCs showed high encapsulation efficiency (90.54 ± 1.7%), uniformparticle size distribution (PDI 0.3-0.5 range) and high colloidal stability with positive zetapotential (+23.86 ± 0.49 mV). DSC and XRD studies confirmed the encapsulation of EFVwithin NLCs. Cytotoxicity studies (MTT assay) revealed excellent cytocompatibility (CC5013.23 ± 0.54 μg/mL). Fluorescence microscopy confirmed the efficient uptake of cationic EFVNLCs,while flow cytometry revealed time and concentration dependant uptake within THP-1cells. Cationic EFV-NLCs showed higher retention and sustained release with 2.32-fold higherpercent inhibition of HIV-1 in infected macrophages as compared to EFV solution at equimolarconcentrations. Interestingly, they demonstrated 1.23-fold superior anti-HIV efficacy over EFVloadedNLCs at equimolar concentrations.
ConclusionCationic NLCs were capable of inhibiting the viral replication at higher limitsconsistently for 6 days suggesting successful prevention of HIV-1 replication in infectedmacrophages and thus can prove to be an attractive tool for promising anti-HIV therapy.
Keywords: Anti-HIV efficacy, Efavirenz, HIV-AIDS infection, Nanostructured lipid carriers, Macrophages, Viral reservoirs -
Pages 433-438Background
Medication errors (MEs) frequently occur in intensive care unit (ICU) admittedpatients. The present study aimed to evaluate the frequency and types of MEs in an open heartsurgery heart ICU and clinical pharmacists’ role in the management of them.
MethodsThis cross-sectional, observational study was performed from October 2016 toMarch 2017 in the Shahid Madani Heart Center. A clinical pharmacist reviewed patients’ files,laboratory data, and physician orders during morning hours. All of the MEs and the clinicalpharmacies’ recommendations for the management of them were analyzed.
ResultsA total of 311 MEs were observed in the medical files of 152 patients. The rate of MEswas 2.04 errors per patient and 0.19 errors per ordered medication. The acceptance rate of MEswas 72.6%. The most type of MEs was ‘forgot to order’ (75 cases, 24.1%) followed by "wrongfrequency" and "adding a drug" in 56 (18%) and 49 (15.8) patients, respectively. Most MEs wereinsignificant.
ConclusionMEs occur at different stages of the therapeutic process in the postoperative cardiacintensive care unit, and clinical pharmacists play an essential role in detecting and managingMEs.
Keywords: Medication error, Clinical pharmacist, Drug-related problems, ICU -
Pages 439-449Background
Supply chain risk management can help companies detect potential hazards,mitigate potential risks, and thereby increase supply chain efficiency. The biopharmaceuticalindustry in Iran has a generic-based pharmerging market. Therefore, identifying risksassociated with the supply chain of those drugs can significantly boost the possibility of successof biopharmaceutical companies. This study is conducted to determine the supply chain riskfactors of biopharmaceuticals companies in Iran.
MethodsThe current research work is a qualitative-quantitative study. A systematic review andinterview with experts (n=14) were conducted to identify potential supply chain risks in thebiopharmaceutical industries. To determine the significance of identified risks, Fuzzy screeningmethod was employed to collect the opinions of experts (n=16) in the biopharmaceuticalindustries.
ResultsBy systematic review and interviews with the biopharmaceutical industry experts, 100potential risks in the biopharmaceutical industry supply chain were identified. These risks weredivided into two general categories namely macro and micro risks. Based on experts’ judgment,77 out of 100 identified risks were eliminated and 23 significant risks were determined. Themost important risks are the Ministry of health (as the regulatory body) conflict of interest, USsanctions, lack of domestic suppliers of essential materials, pseudo-productivity, and moneytransfer related to the bank’s sanctions.
ConclusionDue to the multitude of present risks and the impossibility of controlling all ofthem, it is recommended that managers and producers focus more on controlling the identifiedsignificant risks.
Keywords: Biopharmaceutical, Supply chain, Risk factors, Fuzzy screening, Risk management