Iranian Journal of Pharmaceutical Sciences

Acetaminophen is one of the most important antipyretic and analgesic drugs. It has an excellent efficacy when it is used in therapeutic doses, but in unsafe doses it can be resulted in hepatotoxicity and permanent liver failure. Due to disparities that have been reported between the actual and stated concentration of acetaminophen tablets, we aimed to compare the actual quantity of 8 Iranian generic acetaminophen tablets with the stated amount on the label, using HPLC method. Drug concentration has been measured by HPLC. We performed USP procedure for all models such as tablets, capsule, and oral solution assay preparations USP-36 NF31 by standard preparations. Method validation was achieved. For USP guidelines performance we need to concern on standard references. By chromatography equipment, we used HPLC analyzer 1200 degasser, 1200 bin pump, 1200 ALS, and 1200 VWD. Acetaminophen sample solution included 325 mg weighted quantity of the powder that transferred to a 200 ml volumetric flask in addition to 100 ml of mobile phase. A part of this solution was transferred throughout a 0.5 micrometer permeable filter (or finer). By injecting 10 μL of standard solution into the chromatograph, major peaks are measured as a response. As a final point, calculation of the quantity of acetaminophen in each brand was obtained via specific formula. According to the USP, all brands consisted of 90.0– 110.0 % of the labeled amount of active ingredient (p<0.05). Consequently, The USP standards are met for drugs with different lot numbers by a variety of companies. The differences of clinical attributes of Paracetamol overdose between Iran and other countries may be related to pharmacokinetic and pharmacodynamics issues, metabolism, genetic factors or environmental effects. Further studies are recommended.

Brain-Derived Neurotrophic Factor (BDNF) is a neuroprotectant candidate for neurodegenerative diseases. However, there are several clinical concerns about its therapeutic applications. In the current study, we selected BDNF-mimicking small peptides from phage-displayed peptide library as alternative molecules to the clinical challenges. The peptide library was screened against BDNF receptor (Neurotrophic Tyrosine Kinase Receptor Type 2, NTRK2) and evaluated by ELISA. Polyclonal phage ELISA indicated that target populations were enriched round by round and the panning process was truly effective. The results of monoclonal phage-ELISA showed that all clones had principally bound to NTRK2 but fifteen best clones were sequenced, which twelve of them have SGVYKVAYDWQH (peptide 1) sequence, two pairs were GLHTSATNLYLH (peptide 2), and TVLSHPSTATLI (peptide 3) and one sequence was QQRPYVQDLRLI (peptide 4). Alignment of these peptides and BDNF sequence showed that the resulting peptides conformationally mimicked loop 2 (E40-KVPVSKGQLK-Q51) of BDNF. This region of BDNF is responsible for specific receptor binding and biological activity. According to the similarity of these peptides with BDNF, they could be considered as novel peptidomimetics with therapeutic properties. In addition, modeled peptides were submitted to Protein Model Data Base (peptides 1, 2, 3 and 4 as PMDB ID: PM0081104, PM0081105, PM0081106, PM0081107, respectively).

A novel drug delivery system using poly (ε-caprolactone) - poly (ethylene glycol) -poly (ε-caprolactone) (PCL-PEG-PCL) was established in this study. Ceftriaxone (CTX) was encapsulated within PCL-PEG-PCL
nanoparticles by a double emulsion technique (w/o/w), leading to creation of ceftriaxone-loaded PCL-PEG-PCL (CTX/PCL-PEG-PCL) polymersomes. The resulting polymersomes were characterized by various techniques such as dynamic light scattering (DLS). The release profile of the CTX from the polymersomes was evaluated. The findings showed the successful formation of spherical CTX/PCL-PEG-PCL polymersomes. The loading efficiency of CTX was 17.50± 1.17 %. The results of DLS showed that the polymersomes have size of 115.7±0.48 nm. In vitro release of CTX from polymersomes was remarkably sustained. The sustained release of drug was hypothetically due to the encapsulation of CTX in core of polymersomes. The results indicate the successful formulation of CTX loaded PCL-PEG-PCL polymersomes. It can be concluded that polymersomes may be considered as an effective treatment strategy to improve the therapeutic effect of CTX in the future.

Diabetes is an important risk factor for cardiovascular events. Endothelial dysfunction is the main cause of disability and death in diabetic patients. The present study investigates the effects of metformin and glibenclamide on vasoconstrictive and vasodilative responses in the diabetic rat aorta. Rats were divided into four experimental groups (control, STZ-diabetic, metformin and glibenclamide treated diabetic rats). The treated rats received metformin (300 mg/kg) or glibenclamide (5 mg/kg) daily by gavage for 6 weeks.Thoracic aortic rings were mounted in an organ bath system, then contractile and dilatation responses induced by acetylcholine (ACh), phenylephrine (PE), potassium chloride (KCl), and sodium nitroprusside (SNP) were evaluated in different situations.Blood glucose level in glibenclamide group in days 24 and 45 were significantly lower than diabetic group. Metformin and glibenclamide significantly reduced the contractile responses to higher concentrations of PE (10-6 - 10-5 M) compared to diabetic group. Metformin and glibenclamide significantly reduced the contractile responses to concentrations of KCl (50 and 60 mM) compared to diabetic group. The relaxation responses to Ach 10-8 M, was increased in metformin and glibenclamide groups compared to the diabetic group. The relaxation responses to Ach 10-7 - 10-5 M were significantly higher in both treated groups compared to diabetic group. The chronic administration of metformin or glibenclamide has a significant hypoglycemic effect and improves aortic reactivity to vasoconstrictor and vasodilator agents in STZ-induced diabetic rats. No significant difference was found regarding the effects of metformin and glibenclamide on vasoconstrictive and vasodilative responses in aorta.

Liposomes are the most important lipid-based nanocarriers which are used for encapsulation of both hydrophilic and hydrophobic active compounds. The aim of the present study was to investigate the effect of addition of Gammaoryzanol (GO) in the lipid bilayer formulation on the liposomes characteristics prepared by a modified ethanol injection method. GO bearing nanoliposomes were prepared with different phosphatidylcholine (PC): GO molar ratios, which were selected as the independent variables. Subsequently, the particle size (PS), encapsulation efficiency percent (EE%), and drug release over 24 h (D24h), which were considered as dependent variables, were analyzed and optimized by employing response surface methodology (RSM). Graphical response surface and contour plots were drown to understand the interaction effects of different variables. Finally, the optimum points for the variables levels were obtained from the optimization plot. The mean PS, EE% and D24h of Celecoxib-loaded nanoliposomes were found as 102.6 ± 9.5 nm, 67.6 ± 11.2 %, and 53.97 ± 9.6 %, respectively. The results indicated that both PC: GO and PC: Drug ratio were the important contributing variables for PS, and EE% of nanoliposomes; however, only PC: GO had effect on D24h (P<0.05). The optimum formulation of Celecoxib nanoliposomes, where PC: GO and PC: Drug ratio were 4.6 and 3, have PS = 102 nm, EE% = 74.2 % and D24h = 59.9 %. In conclusion, addition of GO and using ethanol injection method besides RSM techniques presented a simple, rapid, and beneficial approaches for preparation of nanoliposomes with optimum characteristics.

Here in this paper, we report a 31-year-old case admitted with symptoms of hyperthyroidism that was then diagnosed with Grave's disease (GD) and underwent treatments with a low dosage of methimazole (10 mg/day). 20 days after treatments initiations, she developed antithyroid arthritis syndrome. This patient experienced arthritis and arthralgia in at least 4 joints. All autoimmune and microbiologic evaluations were negative. She was then completely recovered without any sequelae within 4 days after drug withdrawal. Arthritis as an adverse effect of methimazole is a major and life-threatening adverse effect which requires immediate drug discontinuation and hospitalization. Contrary to what has been thought. We declare that this adverse effect might not be dose dependent as our case developed arthritis following methimazole therapy with a very low dosage (10 mg/day). The aim of the current case report is to help other physicians in order to diagnose and treat possible cases of antithyroid arthritis syndrome.

Arial parts of Primula genus (Primulaceae) are well known to treat various ailments in Iranian Traditional Medicine. Our preliminary studies demonstrated that the medium polar to polar extracts of Primula auriculata had a significant cytotoxic activity and Induction of apoptosis effects on some cancerous cell lines. The current study focused on phytochemical investigation and characterization the compounds from P. auriculata active extracts. Dried and powdered aerial part of plant was macerated with petroleum ether, dichloromethane, and methanol successively, for 24 hours, three times. Dichloromethane and methanolic extracts were separately examined by different chromatographic techniques such as VLC, CC, and TLC to Fractionation and isolation compounds present in the plant extracts. The structures of purified compounds were elucidated on the basis of spectral data, particularly H-NMR and C-NMR experiments. 2-phenylchromone and 3, 4, 5-trihydroxy benzoic acid was identified for the first time from P. auriculata. In this research we have isolated compounds from pharmacological active extracts which is most likely responsible for cytotoxic action of P. auriculata. Further studies are required to determine activity and mechanism of action of isolated compounds.

This study explores the effects of Interferon-β characteristics such as country of origin, injection frequency and method, monthly cost, effectiveness, and side effects on multiple-sclerosis patients’ willingness to pay. For this purpose, MS patients with a history of using Interferon-β were studied from the three major Isfahan MS centers. Choice sets were designed with a combination of attributes and levels. The variables in this experiment included interferon-β with different levels assigned to each of its attribute. Patient preferences and willingness to pay were calculated through Discreet Choice Experiment. The statistical population consisted of 358 patients deemed eligible for the study. They responded to the questionnaire and took part in interviews. Results showed that the highest willingness-to-pay value of US$ 223 as determined by MS patients belonged to a change of effectiveness from moderate to high. Side-effects and ease of use ranked next among patient preferences. Country of origin recorded the lowest value of the willingness-to-pay parameter. Evaluation of MS patients' preferences as reflected in their willingness to pay plays an important role in patient’s adherence to treatment to achieve more effective results. Due to the variety of drugs in this category, it is necessary to identify and prioritize those features that are of interest to patients and that increase their utility relative to IFN-β drugs.

Pramipexole is the mostly prescribed drug in patients with Parkinson disease. The incidence of Parkinson disease is related to aging and mostly developed in elderly people with difficulty in swallowing or dysphagia. In the current study we aimed to develop an orally fast disintegrating tablet (ODT) of pramipexole as a preferable alternative in geriatric patients. Hence, the fast disintegration is a critical for ODTs, the effects of four different superdisintegrants including, crospovidone, croscarmellose, sodium starch glycolate, and agar were evaluated on physical characteristics of the tablets. All of the formulations were prepared through direct compression method using aspartame and mannitol as taste masking agents. The flow properties of all of the mixtures were in the acceptable limits. Croscarmellose and Avicel® were chosen as the best superdisintegrants which resulted in the lowest disintegration time and the least friability. In subsequent studies, a 32 full factorial design was adopted to assess the impact of different amounts of croscarmellose and Avicel®. The overall results suggest that the tablet containing 2.5 mg croscarmellose and 70 mg Avicel® as superdisintegrants is the best formulation. Mean hardness, disintegration time, friability, and the drug release percent during 5 min for the optimized formulation were confirmed 42.05 ± 4.6 Kg/cm2, 24.98 ± 6.8 Sec, 0.13 %, and 95.52 ± 2.23% , respectively.

Although quinolone resistance results mostly from chromosomal mutations in Klebsiella pneumoniae, it may also be mediated by plasmid – encoded qnr determinants. Plasmid-mediated quinolone resistance (PMQR) was increasingly identified in Enterobacteriaceae family worldwide. The aim of this study was to investigate the prevalence of qnr genes in clinical isolates of Klebsiella pneumoniae spp in Zahedan, south-East of Iran. In this sectional-descriptive study which was performed in 2013, clinical isolates of k. pneumoniae (n=184) were collected from patients referred to 3hospitals of Zahedan. The presence of the qnr gene was screened by PCR using specific primers for qnrA, qnrB, qnrS and qnrC in extracted plasmid DNA. Of 184 K. pneumoniae clinical isolates, 45 isolates were positive for the qnr gene. The prevalence of qnrA, qnrB and qnrS clusters among these isolates were 8 (17.7%), 22 (48.8%), 4(8.88%) respectively and qnrC was not identified in any isolate. Another 6(13.33%) possessed both qnrA and qnrB genes and 5(11.11%) possessed both qnrB and qnrS. qnr are widely distributed worldwide. Community-acquired and nosocomial pathogens and the emergence of qnr-mediated quinolone resistance among clinical K.pneumoniae isolates are described for the first time in Iran.