Research/Original Articles


A Participative Process of Strategy-Making and Firm Performance in Iranian Pharmaceutical Companies

Seyed Abolfazl Abolfazli, Mehdi Mohammadzadeh, Farzad Peiravian, Seyed Hesam Sharifnia

Iranian Journal of Pharmaceutical Sciences, Vol. 14 No. 1 (2018), 15 January 2018, Page 1-14
https://doi.org/10.22037/ijps.v14.40667

Pharmaceutical companies are regarded as principal contributors to national economies all over the world owing to their substantial assistance to public health system; GDP, employment, and market growth. Consequently, pharmaceutical managers must take the necessary steps to improve strategy-making and firm performance. This study investigates the relationship between four conventional modes of strategy-making process and performance in pharmaceutical companies in Iran. This paper argues that small or knowledge-based pharmaceutical companies, similar to large pharmaceutical companies, place differing emphasis on strategy-making and could apply different approaches to strategy-making. Furthermore, the present research offers an explanation of the nature of these processes in pharmaceutical companies and hypothesizes how they are related to firm performance. It then describes the results of an empirical study on the strategy-making processes of pharmaceutical companies in Iran. Analysis of the data obtained from 125 pharmaceutical companies indicates that participative approaches to strategy-making exist in these pharmaceutical companies and could have a significant and strong relationship with firm performance.

Predictive Modeling of Phenylpiperazine Derivatives for Renin Inhibition

Jimish R Patel, Laxman M Prajapati

Iranian Journal of Pharmaceutical Sciences, Vol. 14 No. 1 (2018), 15 January 2018, Page 15-26
https://doi.org/10.22037/ijps.v14.40668

The renin–angiotensin–aldosterone system is the well-established endocrine system having significant role in preserving hemodynamic stability. Renin is secreted from the juxtaglomerular cells of the kidney. Phenylpiperazine derivatives have been reported as human renin inhibitor. To do the study, a predictive QSAR modeling for 27 phenylpiperazine derivatives as renin enzyme inhibitors was used. The IC50 values for purified human renin were taken as biological activity. Physicochemical properties were calculated on Dragon software, version 5.5. Hierarchical Multiple Regression was performed to obtain quantitative structure-activity relationship model which again validated internally and externally. The selected best QSAR model had the correlation coefficient (R2) of 0.843, and predicted correlation coefficient (R2pred) of 0.867. The predictive ability of the selected model was established by leaving one-out cross-validation. Different Rm2 matrices were also calculated to validate the model externally. The quantitative structure activity relationship study indicates that CIC2, BIC2, and R7v descriptors have a very important role in renin enzyme and ligand interaction. The developed model can be applied to design new effective renin enzyme inhibitors.

Phytochemical Screening, Phenolic Content and Antioxidant Activity of Citrus aurantifolia L. Leaves Grown in Two Regions of Oman

Jokha Al Namani, Esra Baqir, Ajwaa Al Abri, Tamadher Al Hubaishi, Asif Husain, Shah Alam Khan

Iranian Journal of Pharmaceutical Sciences, Vol. 14 No. 1 (2018), 15 January 2018, Page 27-34
https://doi.org/10.22037/ijps.v14.40669

Lime or Citrus aurantifolia L., is a small citrus fruit that belongs to the family Rutaceae. The fruit and leaves of C. aurantifolia have been used traditionally for weight loss, skin care, relief from constipation and treatment of scurvy, etc. The purpose of this study was to determine the flavonoid, total phenolic content, and investigation of anti-oxidant potential of Citrus aurantifolia leaves grown in Oman. Lime leaves were collected from Batinah (Nakhal) and Ad-dakhiliya (Nizwa) region of Oman. The leaves were dried, powdered, and extracted with ethanol using a hot extraction method. Standard chemical tests were used to check the presence of secondary plant metabolites in the lime leaves extract. Quantitative analysis of the phenolics and flavonoids were done by colorimeteric methods. The antioxidant activity was assessed by DPPH and phosphomolybdenum in vitro assay methods respectively. Chemical analysis of the lime leaves extract showed the presence of major secondary plant metabolites. The obtained results revealed variation in the content of flavonoid (41.38-64.2 μg of QE/mg of dry extract) and phenolic compounds (96.55-322.57 μg of GAE/mg of dry extract). Both the lime leaves extracts from Nakhal and Nizwa showed concentration dependent moderate anti-oxidant activity (11.79-56.89 and 10.11-51.91%). Lime leaves from Batinah region also exhibited better total antioxidant capacity calculated with reference to the standard gallic acid. The aerial part of C. aurantifolia seems to be a rich source of flavonoids. Further studies are recommended to isolate and quantify the pure phytoconstituents from lime leaves grown in the Batinah (Nakhal) region which might serve as natural antioxidants in food and drug industry.

Effect of Powder Sizes, pH of Water, Ultrasound and Method of Distillation on Extraction of Fennel Essential Oil and Anethole Content

Mahdi Tavakolizadeh, Ghazaleh Hadian, Mohammad Reza Khoshayand, Faraz Mojab

Iranian Journal of Pharmaceutical Sciences, Vol. 14 No. 1 (2018), 15 January 2018, Page 35-44
https://doi.org/10.22037/ijps.v14.40670

The essential oils are frequently used in food processing industry, perfumery, cosmetics, and pharmaceuticals. Most of the oils were obtained by steam distillation and water distillation. It is necessary to specify the best conditions of essential oils production to get much more major compound(s) and higher yield oil. So, fennel oil was selected in this study. The objective of this work was to identify the effect of powder’s particle size, pH of water, method of distillation and using ultrasound on extraction of fennel essential oil (and its major constituent, anethole). We used a statistical method called D-optimal Design that appointed pH, particle size, and method for each assay. First, the seeds powder distillated directly. In the second series, the seeds were placed in an ultrasonic apparatus for 30 minutes. The essential oils were subsequently isolated by two methods, hydro-distillation, and steam-distillation in different sizes and pH in Clevenger apparatus. Gas chromatography was used to determination of major component (E-anethole) in fennel essential oils. Finally, optimum conditions according to the statistical results are as follows: Method: steam distillation, and mesh size: 50. So it shows that steam distillation is more efficiently than water distillation.

Simultaneous Estimation of Amlodipine Besylate and Nebivolol Hydrochloride in Pharmaceutical Tablets Formulation by RP-HPLC Using PDA Detector

Ashutosh Kumar, Manidipa Debnath, Mendeli Sreenu, Mahesh Kumar Singh

Iranian Journal of Pharmaceutical Sciences, Vol. 14 No. 1 (2018), 15 January 2018, Page 45-56
https://doi.org/10.22037/ijps.v14.40671

The present work was undertaken with the aim to develop and validate a rapid and consistent RP-HPLC method in which the peaks will be appear with short period of time as per ICH Guidelines.The separation was achieved on a stainless steel analytical column, Eclipse XDB plus C18 column (4.6 X 150 mm; 5 μm) in an isocratic mode. The mobile phase was composed acetonitrile and 0.01 M ammonium acetate (pH adjusted to 4.5 using glacial acetic acid), which were mixed in the ratio of 50: 50. The flow rate was monitored at 1.0 mL/min. The wavelength selected for detection was 265 nm. The retention time found for amlodipine besylate and nebivolol hydrochloride was 2.967 and 3.510 min, respectively. The % recovery was 100.20- 100.86 for amlodipine and 100.20 - 100.78 for nebivolol. The linearity was established in the range of 5-25 μg/mL for amlodipine and 10-50 μg/mL for nebivolol. The slope, intercept, and correlation coefficient were found to be 314.2x, +162.4, and 0.999 for amlodipine besylate and 248x, -305.7, and 0.9998 for nebivolol hydrochloride, respectively. The limits of detection for amlodipine besylate and nebivolol hydrochloride obtained by the proposed method was 0.07 and 0.20 μg/ml and the limits of quantification for amlodipine besylate and nebivolol hydrochloride obtained by the proposed method was 0.23 and 0.61 μg/mL, respectively. The method was found to be suitable for the quality control test of amlodipine besylate and nebivolol hydrochloride simultaneously in a bulk drugs as well as in a formulations.

This study investigated the water absorption of chitosan, collagen, and chitosan/collagen blend membranes exposed to gamma-ray irradiation. These membranes were produced via the solvent evaporation method. All membranes then underwent irradiation at 15 or 25 kGy gamma-ray doses, while membranes without irradiation were used as controls. After immersing the membranes in distilled water for up to 180 min, water absorption was determined by calculating the percentage weight increase. The results demonstrated some changes in the water absorption curves with differing membranes and irradiation doses. However, after 60 min, all of the water absorption curves plateaued. With respect to membrane type, the chitosan membranes exhibited the highest water absorption; the blend displayed the lowest; and also the collagen was in the mid range. With the use of higher radiation doses, the chitosan membranes displayed lower water absorption, which was also true of the blend but not collagen membranes. To conclude, the water absorption of chitosan, collagen, and chitosan/collagen blend membranes with and without gamma-ray irradiation initially increased steadily and then plateaued. The water absorption values of the irradiated blend membranes were the lowest; however, the values were relatively steady.

Prioritizing the Factors Affecting the Abuse of Pharmaceutical Opioids by Applying Topsis

Farahnaz Zeinali, Mehdi Mohammadzadeh, Jamshid Salamzadeh

Iranian Journal of Pharmaceutical Sciences, Vol. 14 No. 1 (2018), 15 January 2018, Page 67-74
https://doi.org/10.22037/ijps.v14.40673

Human societies have witnessed the phenomenon of ever-increasing use of pharmaceutical opioids for a long time. Moreover, cultural, social, and economic aspects in any community have undergone the negative effects of the growing tendency toward opioids addiction. Since abusing pharmaceutical opioids is a serious problem, it is important to recognize and prioritize the factors influencing this abuse. This paper concentrates on assessing the priorities of variables which have effects on the abuse of pharmaceutical opioids in order to help the policy makers to make correct decisions to reduce the abuse of opioids.Topsis is applied as a method for Multi-Attribute decision making, which prioritizes alternatives in a simple but efficient way. Topsis method identifies the closeness of each alternative to the ideal solution. In this method, each alternative should have the shortest distance from the best solution and the farthest distance from the worst solution. According to the findings, ―family role‖ and ―extra prescription‖ are the most important factors in variables.

Evaluation of Ibuprofen Release from Gelatin /Hydroxyapatite /Polylactic Acid Nanocomposites

Zohre Nabipour, Mohammad Sadegh Nourbakhsh, Mohammad Baniasadi

Iranian Journal of Pharmaceutical Sciences, Vol. 14 No. 1 (2018), 15 January 2018, Page 75-84
https://doi.org/10.22037/ijps.v14.40674

Gelatin-hydroxyapatite-polylactic acid (PLA) nanocomposites were synthesized using five different formulations. The nanocomposites were loaded with ibuprofen and the amount of drug in the carriers was determined. X-ray diffraction (XRD) analysis was conducted before and after drug loading to ensure the presence of ibuprofen on the nanocomposites. Drug delivery was evaluated in phosphate buffered saline (PBS) solution at pH 7.4 and 37°C. The results of XRD analysis showed acceptable synthesis of hydroxyapatite and the composites, confirming the loading of ibuprofen onto the synthesized nanocarriers. The results showed that maximum drug loading (58.2%) was recorded for sample D (30% gelatin, 40% nHA and 30% PLA), and minimum loading was recorded for sample E (30% gelatin, 30% nHA and 40% PLA). The maximum percentage of drug release over the course of 72 h (95.8%) was for nanocomposite D (30% gelatin, 40% nHA and 30% PLA). The minimum percentage of drug delivery (77%) was for nanocomposite E (30% gelatin, 30% nHA, 40% PLA), which contained the maximum PLA content.

Inhibition of Foot-and-Mouth Disease Virus Replication by Hydro-alcoholic and Aqueous-Acetic Acid Extracts of Alhagi maurorum

Yasmin Shakiba, Seyedeh Elham Rezatofighi, Seyyed Mansour Seyyed Nejad, Mohammad Roayaei Ardakani

Iranian Journal of Pharmaceutical Sciences, Vol. 14 No. 1 (2018), 15 January 2018, Page 85-96
https://doi.org/10.22037/ijps.v14.40675

Foot-and-mouth disease (FMD) is a major infectious disease of cloven-hoofed animals that is caused by the FMD virus (FMDV). This disease has significantly adverse economic impacts; therefore, rapid control measures are urgent. Hydro-alcoholic and aqueous-acetic acid extracts of A. maurorum were prepared and their anti-FMDV activity was evaluated. Gas Chromatography–Mass Spectrometry (GC-MS) analysis of methanolic and ethanolic extracts was performed to find the likely active compounds of A. maurorum. The cytotoxicity of the extracts was assayed and the antiviral activity of them was evaluated by measuring the percentage of viable FMDV infected-cells via the MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay at different stages of the virus replication cycle. The results indicated that the plant extracts exhibit antiviral activity against FMDV at all stages of the experiment, although the most significant effects were observed in virucidal and pre-treatment assays. GC-MS of the extracts resulted in the separation of 3 and 2 main peaks for the methanolic and ethanolic extracts respectively. The major compound was found to be 1, 2-Benzenedicarboxylic acid, diisooctyl ester. These findings represent the anti-FMDV activities of A. maurorum extracts at several stages of the virus replication cycle; therefore, it could be considered for the potential development of anti-FMDV therapeutics.

Influence of Chemical Permeation Enhancers on the in vitro Skin Permeation of Minoxidil through Excised Rat Skin: A Mechanistic Study

Eskandar Moghimipour, Anayatollah Salimi, Ali Talebpour Jahromi

Iranian Journal of Pharmaceutical Sciences, Vol. 14 No. 1 (2018), 15 January 2018, Page 97-110
https://doi.org/10.22037/ijps.v14.40676

Minoxidil, a pyrimidine derivative (2, 4-diamino-6-piperidinopyrimidine-3-oxide) is the only topical medical treatment with proven efficacy for the treatment of androgenic alopecia that showed low skin penetration and bioavailability. The main aim of this research was to investigate the effect of some permeation enhancers on the in vitro skin permeability of minoxidil. Minoxidil permeability experiments through rat skin pretreated with some of permeation enhancers namely, Urea, Eucalyptus oil and Menthol were performed in fabricated Franz diffusion cells and compared with hydrated rat skin as control. The permeability parameters evaluated include steady-state flux (Jss), permeability coefficient (Kp), and diffusion coefficient (D). The penetration enhancer’s permeability enhancement mechanisms were investigated by comparing of changes in peak position and their intensities of asymmetric (Asy) and symmetric (Sym) C-H stretching, C=O stretching, C=O stretching (Amide I) and C-N stretching of keratin (Amide II) absorbance using Fourier transform infrared spectroscopy (FTIR), as well as by comparing mean transition temperature (Tm) and their enthalpies (ΔH) using differential scanning calorimetry (DSC). Minoxidil permeability parameters through rat skin, were evaluated with and without chemical enhancers such as Eucalyptus oil, menthol, and urea. The skin showed barrier for minoxidil permeability through whole skin and that diffusion into the skin was the rate-limiting step for drug flux. Urea, Eucalyptus oil, and Menthol were the most effective enhancers as they increased flux 1.86, 2.16, and 1.75 times and diffusion coefficient 3.25, 1.34 and 2.16 folds in comparison with hydrated skin, respectively. FTIR and DSC results showed lipid fluidization, extraction, disruption of lipid structure and irreversible denaturation of proteins in the SC layer of skin by permeation enhancers.