Research/Original Articles

Formulation, Design, and Optimization of Taste Masked Effervescent Tablet Containing Methocarbamol

Somayeh Taymouri, Abolfazl Mostafavi, Hamid Mahmoodi

Iranian Journal of Pharmaceutical Sciences, Vol. 17 No. 4 (2021), 1 Mehr 2021, Page 1-14

Methocarbamol is a skeletal muscle relaxant drug. In this study, we investigated the potential of developing methocarbamol effervescent tablets to facilitate drug administration. Effervescent tablets containing 1000 mg methocarbamol were prepared using the direct compression method. The effect of various formulations parameters such as citric acid, sodium bi-carbonate, PEG 6000, and PVP k30 on different physicochemical properties of tablets was evaluated at two levels. Different formulations with various amounts of mentioned excipients and the constant amount of methocarbamol, sucralose, mannitol, and different flavoring agents were prepared, and their properties included hardness, friability, pH effervescent time, CO2 content, and taste were studied. The optimized formulation was B8, which contained 400 mg of citric acid, 525 mg of sodium bicarbonate, 226.5 mg of PVP k30, 113.2 mg of PEG 6000, 100 mg of mannitol, and 30 mg of sucralose. This formulation had an effervescent time of 112.67± 2.05 seconds, hardness of 71.10± 2.51 N, and pH of 6.01±0.02. Statistical analysis by Design-Expert software showed that the hardness of tablets is mainly affected by the amount of PEG 6000. Volunteers reported that sour cherry had the most pleasant taste to them. In conclusion, current effervescent tablets are shown to be suitable vehicles for methocarbamol with potential for use in patients with swallowing problems and will enhance patient compliance.

Mix vaginitis refers to at least two potential pathogenic microbes in the vagina. Recently, the popularity of nanoparticles is increasing; these materials have been widely used as an antimicrobial agent in the treatment of chronic infections in which silver nanoparticles (AgNPs) are more widely considered. We aimed to establish a mixed vaginitis model in adult mice with Candida albicans and Escherichia coli, then evaluated the effect of AgNPs and L. carnitine (LC) to treat the vaginitis. In our study, the microdilution method and minimum biofilm inhibitory concentration were used for the antimicrobial activity of AgNPs. Vaginitis was made by intra-vaginal inoculation of 107 CFU/ml of both E. coli/C. albicans in adult NMRI mice. Mice were classified into 8 groups: (1) healthy mice without any treatment, (2) mice were infected intravaginally with equal volumes of C. albicans and E. coli suspensions, (3) healthy mice that received daily intraperitoneal injection of 250 mg/kg LC for two weeks, (4) infected mice that treated with a daily injection of 250 mg/kg LC for two weeks, (5) healthy mice that received daily intravaginal inoculation of 250 ppm of AgNPs for two weeks, (6) infected mice treated with daily intravaginal inoculation of 250 ppm AgNPs for two weeks, (7) healthy mice that received daily intravaginal inoculation of 250 ppm AgNPs and a daily injection of 250 mg/kg LC for two weeks, and (8) mice treated with daily intravaginal inoculation of 250 ppm AgNPs and a daily injection of 250 mg/kg LC for two weeks. All treatments with AgNPs and LC were daily for two weeks. A vaginal smear was taken throughout the experiment, and tissue sections were prepared using the hematoxylin-eosin method. The results showed that the 50% inhibitory concentration (IC-50) of AgNPs for E. coli, C. albicans, and their mixture was 96.84, 11.23, and 35.67 ppm, respectively, and their IC- 90 values were 201.77, 105.51, and 173.13 ppm, respectively. MBIC-90 % of AgNPs for E. coli, C. albicans, and the mixture of them were 500, 125, and 250 ppm, respectively. The estrus cycle in treated mice was similar to intact mice, and the order of their vaginal tissue sections confirmed the treatment of mixed vaginitis. In conclusion, co-administration of AgNPs and LC may eliminate the adverse effect of AgNPs and mixed vaginitis.

Antioxidant Activity and Cytotoxic Effects of Hypnea musciformis on MCF7 and MDA-MB-231 Cell Lines

Alireza Moulazadeh, Razieh Ranjbar, Amin Dakhili Ardestani, Sohrab Najafipour

Iranian Journal of Pharmaceutical Sciences, Vol. 17 No. 4 (2021), 1 Mehr 2021, Page 33-46

Free radicals impair the cellular and tissue homeostasis, which can cause to cancer. Hypnea musciformis is a red seaweed and rich source of secondary antioxidant metabolites. These metabolites probably are effective in cancer treatment. In the present study, the phenolic and flavonoid content of the hydro-methanolic extract of Hypnea musciformis were determined respectively by the Folin-Ciocalteu and aluminum-chloride assay. The monovalent reducing power and total radical scavenging activity of the extract were also evaluated respectively by FRAP and DPPH assay. The cytotoxic effects of the extract were evaluated by MTT assay on MDA-MB-231 and MCF7 cell lines. Morphological changes of the cell lines were also examined by invert microscope. Statistical analysis was performed using t-test in GraphPad Prism 8.0.2 software. The results of the study indicate that the phenolic and flavonoid contents of the extract respectively were 14.05± 2.39 μgGAE/mg and 39.08± 8.78 μgQE/mg. The monovalent reducing power of the extract was 243.32± 27.86 μmol Fe2+/g and its total radical scavenging activity (in 1000 μg/mL) was 18.75± 1.51 %. The cytotoxic effects of the extract on MDA-MB-231 were higher than MCF7 cell line,   significantly (P <0.05). The IC50 value of the extract on MDA-MB-231 and MCF7 cells respectively was 634.5 and 826.8 μg/mL, after 72 hours of incubation. The morphological changes of treated cell line include cell granulation, cell contraction and rupture in a concentration and time dependent pattern. The cytotoxic effects of Hypnea musciformis extract were not dependent on estrogen, progesterone and HER2 receptors. Therefore, the hydro-methanolic extract of Hypnea musciformis probably is a favorable option in drug discovery against the triple-negative tumors.

Metal (II) Complexes of some Carboxylic group Drugs: Chelation, Characterization, Antibacterial, Analgesic, and Toxicology Studies

Ikechukwu P. Ejidike, Mercy O. Bamigboye, Chima B. Njoku, Misitura Lawal

Iranian Journal of Pharmaceutical Sciences, Vol. 17 No. 4 (2021), 1 Mehr 2021, Page 47-64

The present work focuses on the synthesis and biological evaluation of metal complexes of mixed acetylsalicylic acid and para-aminobenzoic acid in ratio 1:1:1 to give a complex type: [M(ASA)(PABA)(H2O)n(Cl2)x](Cl2)y (where M = Cu(II), Cd(II), Ni(II), Fe(III), or Mn(II); ASA = Acetylsalicylic acid; PABA = para-aminobenzoic acid; n = 0 or 2; x = 0 or 1; y = 0 or 1). The metal complexes were obtained by a refluxing method and characterized by elemental analysis, melting point, conductivity measurements, ultraviolet-visible absorption, and infrared spectroscopy. The conductance measurement indicates the non-electrolytic nature of the complexes. The octahedral environment has been proposed for the complexes except for Cd (II) complex. The level of toxicity of the synthesized complexes was determined in vivo. [Cu(ASA)(PABA)(H2O)2], [Cd(ASA)(PABA)]Cl2, and [Mn(ASA)(PABA)(H2O)2] exhibited higher enzymatic activities in the serum and kidney homogenates of the Wister rats investigated. The acetic acid-induced writhing model method was used in the evaluation of the analgesic activities of the prepared complexes. Metal complexes of Cu (II), Cd(II), Ni(II), Fe(III), and Mn(II) exhibited percentage writhing inhibition of 67.61, 43.87, 60.42, 70.45, and 52.34 % respectively. The complexes proved to be more effective than their parent-free ligands with Fe (III) possessing the highest analgesic potentials. The in vitro antimicrobial activity against bacterial strains was studied using the agar well diffusion procedure. It was also observed that the complexes exhibited higher bacteriostatic activities than the free ligands.

Melanogenesis Inhibitory Effects of Ethanol Extract of Perilla frutescens’s Leaves on B16 Melanoma Cells

Thuan Van Tran, Quynh-Nhu Nguyen-Ho, Truong-Van Nguyen-Thien, Quang Ton-That, Thuoc Linh Tran, Hieu Tran-Van

Iranian Journal of Pharmaceutical Sciences, Vol. 17 No. 4 (2021), 1 Mehr 2021, Page 65-72

Perilla frutescens (L.) Britt. is a Vietnamese herb containing many polyphenol compounds potential on antioxidants and tyrosinase inhibitors for cosmetic applications. Natural compounds and products have got more attention as they have less undesirable side effects and satisfy the diverse needs of consumers that include anti-melanogenesis, antioxidation, etc. This study evaluated the antioxidant capacity, inhibition of melanin synthesis in B16 melanoma cells of perilla leaves ethanol extract (PEE). PEE showed the high antioxidant properties in vitro by 2, 2′-diphenyl-1-picrylhydrazyl radical assay (DPPH) and Ferric reducing antioxidant power (FRAP). In addition, PEE has inhibitory activities for mushroom tyrosinase (TYR). The results showed that concentrations of 100 - 300 μg/mL of PEE were not affected on B16 cell viability. In B16 cells, melanin content and cellular tyrosinase activity were significantly decreased in PEE-treated cells in a dose-dependent manner. These results suggested that Perilla frutescens (L.) Britt. had a great potential as natural sources which could be used as agents in skincare products.

Evaluating Antibiotics Administration’s Pattern and Its Financial Burden in a Teaching Hospital in Iran

Pouria Esmaeil Soufian, Mahdi Bagheri, Abdol Majid Cheraghali

Iranian Journal of Pharmaceutical Sciences, Vol. 17 No. 4 (2021), 1 Mehr 2021, Page 73-86

Indiscriminate use of antibiotics frequently leads to healthcare complications, including an increase in the number of resistant microorganisms and patient hospitalization period, which subsequently results in a financial disadvantage for the patients and the country's healthcare system. Therefore, researches on causes of such malpractices could shed light on ways to prevent further impacts on health care system. The purpose of this study is to investigate antibiotics administration’s pattern and its financial burden in a teaching hospital in Iran in 2018. This descriptive cross-sectional study is based on data obtained from the hospital medicine statistics unit. The share of antibiotics in the total cost of medicine expenditure has been calculated and the cost burden of top 10 antibiotics and their administration in different hospital departments were also assessed. According to the data obtained, about 12.2% of the total cost of medication expenditure in the hospital in 2018 was attributed to the administered antibiotics. The financial burden due to the use of all medicines and antibiotics in 2018 per patient admitted in the hospital were 4,327,912 Rials (1,030 USD) and 529,400 Rials (126 USD), respectively. The total use of these antibiotics was 56.77 DDD/100Bed-Days. Financial burden of the injectable forms of antibiotics is higher than other pharmaceutical forms and the intensive care unit showed the most use of these antibiotics. The 10 most high-cost administered antibiotics included Meropenem, Ciprofloxacin, Clindamycin, Vancomycin, Teicoplanin, Levofloxacin, Metronidazole, Azithromycin and Ceftriaxone, respectively. Compared to the other published data regarding administration of antibiotics in other hospitals, this study showed that there is a need for more surveillance on rational administration of the antibiotics in this hospital.

Fatty Acid Composition of the Fruits of Four Varieties of Pistacia vera L

Sid Ahmed Boualem, Mohamed Ghrab, Djilali Bouhadi, Abdelkader Elouissi

Iranian Journal of Pharmaceutical Sciences, Vol. 17 No. 4 (2021), 1 Mehr 2021, Page 87-96

The oil content, fatty acid compositions of pistachio nut (Pistacia vera L.) samples corresponding to four different varieties (Achouri, Adjmi, Batouri and Mateur), all cultivated in Algeria were determined. The fatty acid profiles of the oil extracted by the Soxhlet apparatus from four main commercial pistachio varieties, were determined by gas chromatography: palmitic (C16:0), palmitoleic (C16:1), margaric (C17:0), margarolic (C17:1), stearic (C18:0), oleic (C18:1), linoleic (C18:2), and linolenic (C18:3), oleic acid has been found as the most common monounsaturated fatty acid. Linoleic acid has the highest percentage among polyunsaturated fatty acids. There have been significant differences among pistachio cultivars regarding unsaturated fatty acids. Based on the oleic to linoleic acid (O/L) ratio, a quality index was determined for these four varieties: Achouri (3.39)  Batouri (3.12)  Adjmi (2.89)  Mateur (2.88). Principal Component Analysis (PCA) showed the pistachio varieties division into three distinct groups: Adjmi and Mateur (rich in C18.2), Batouri (rich in C16.1, C18.3 and C18.1), Achouri (rich in C16.0, C18.1).

The Pattern of Albumin Consumption in Teaching University Hospitals in Northeastern Iran

Samaneh Mollazadeh, Taraneh Tavanaei Tamanaei, Sahar Oghazian, Sabah Oghazian, Mohammad Bagher Oghazian

Iranian Journal of Pharmaceutical Sciences, Vol. 17 No. 4 (2021), 1 Mehr 2021, Page 97-106

Insufficient information on accurate indications of albumin administrations and the lack of acceptable protocols emphasize the importance of performing further studies on the albumin consumption. So, the current study aimed to explore the albumin administration in the teaching hospitals to not only provide an effective pattern, but also to provide low-cost strategies for rational use of this drug. Herein, one hundred patients were given albumin during the study period, who were randomly selected from hospitals affiliated with a large public university. The collected data were analyzed using IBM SPSS Statistics (version 22). Our findings showed that 46% of the patients finally received albumin in terms of the approved guideline. In total, 777 albumin vials were used for 100 cases, for whom 414 vials (53.2%) were rationally prescribed. The albumin was frequently administrated in the ICU wards with 62% of total vials. In accordance with some previous studies, our results demonstrated that most of the albumins were prescribed inappropriately, which impose high-cost on the patients as well as on health care system. Therefore, long-term monitoring of albumin therapy implemented by trained physicians, is suggested to promote rational albumin consumption.

Some Selected Phytoconstituents from Rhus succedanea as SARS CoV-2 Main Protease and Spike protein (COVID-19) Inhibitors

Prasanth D. S. N. B. K., Suneetha Achanta, Siva Prasad Panda, Lakshmana Rao Atmakuri, Chakravarti Guntupalli, Narayana Rao Alla, Risy Namratha Jamullamudi, Jahasultana Mohammed, Haritha Lanka, Teja Nayudu, Sandhya Tera, Bhargavi Koti, Monika Chigurupati, Likhith Kolla, Praveena Tata, Purnadurganjali Chittiprolu

Iranian Journal of Pharmaceutical Sciences, Vol. 17 No. 4 (2021), 1 Mehr 2021, Page 107-122

Rhus succedanea (Anacardiaceae) was used to treat multiple human afflictions. Literary works demonstrate that it has many biological activities. Today's research aims to recognize Rhus succedanea Phyto-derived anti-viral compounds against the main protease and spike protein of the viral agent of COVID-19 (SARS-CoV-2) gain insight into the molecular interactions. In the current study, ten molecules taken from R. succedanea are analyzed through docking, derived from the PubChem database. Docking experiments with Autodock vina and PyRx tools were conducted. AdmetSAR and DruLito servers were eventually used for drug-like prediction. Our research shows that the phytoconstituents from R. succedanea, namely, Amentoflavone, Rhoifolin, and Agathisflavone acts against SARS CoV-2 main protease with the binding affinity of -9.3, -8.6 and -8.4 Kcal/mol; Hinokiflavone Robustaflavone and Amentoflavone acts against the SARS-CoV-2 receptor-binding domain of spike protein with a binding affinity of -10.5, -10.4 and -10.1 Kcal/mol respectively. These phyto-compounds can use contemporary strategies to develop effective medicines from natural origins. The substances identified potential anti-viral as likely. However, In-vitro studies are even more necessary to assess their effectiveness versus SARS CoV-2.