Open Access Short Research Article

Endothelin-1 (1-31) Causes the Migration of Vascular Smooth Muscle Cells through Endothelin ETA Receptor

Yoji Kyotani, Jing Zhao, Kentaro Ozawa, Takahiko Nakagawa, Francesco A. Bolstad, Masanori Yoshizumi

Journal of Pharmaceutical Research International, Page 1-7
DOI: 10.9734/BJPR/2016/29824

Endothelin-1 (ET-1) is predominantly expressed in endothelial cells to modulate physiological actions, such as vasoconstriction and cell proliferation. It acts as an autocrine and paracrine factor, and has been reported to be found in increased levels in the blood of patients with hyperlipidemia and atherosclerosis. The excessive proliferation and migration of vascular smooth muscle cells (VSMCs) characterize the progression of atherosclerosis. Thus, ET-1 is currently believed to be an important factor for atherosclerosis. Endothelin-1 (1-31) is a relatively recently discovered form of ET and is generated from big ET-1 by chymase, which is predominantly expressed in mast cells. Recently, the elevated concentration of circulating ET-1 (1-31) in patients with acute myocardial infarction has been reported. In this study, we investigated whether ET-1 (1-31) could induce VSMC migration and compared its effect with that of ET-1. ET-1 (1-31) significantly stimulated rat aortic vascular smooth muscle cell (RASMC) migration in a concentration dependent manner. ET-1 (1-31) at 100 nM caused a 1.38-fold increase in RASMC migration whereas ET-1 at the same concentration resulted in a 1.60-fold increase. The ET-1 (1-31)-stimulated RASMC migration was significantly inhibited by BQ123, a specific ETA receptor antagonist, but not by BQ788, a specific ETB receptor antagonist. These data suggest that ET-1 (1-31) stimulates the VSMC migration through ETA receptors but not ETB receptors. The findings presented in this paper bring us one step closer to understanding the mechanisms involved in atherosclerosis.

Open Access Original Research Article

Pharmacokinetics and Bioequivalence Study of Two Proton Pump Inhibitor Products

Ehab Ibrahim Taha, Fathy Ibrahim Abd-Alla

Journal of Pharmaceutical Research International, Page 1-8
DOI: 10.9734/BJPR/2016/29952

Omeprazole (OPZ) efficiently suppresses acid secretion in the parietal cells of the stomach. It is widely recommended as proton pump inhibitor (PPI) in Egypt. Presence of many products containing omeprazole available in the Egyptian market raises questions of generic substitution and/or therapeutic equivalence. The aim of the study was to compare the pharmacokinetic parameters and relative bioequivalence properties of two oral omeprazole formulations, Gastroloc® and Pepzol® enteric coated capsules, in healthy subjects. A randomized, two-way crossover study was conducted to study the pharmacokinetic parameters of the OPZ products in 24 healthy human volunteers in compliance with the Declaration of Helsinki and ICH guidelines. After oral administration and at specified time intervals, blood samples were collected and analyzed for plasma OPZ content using a validated HPLC method. The Pharmacokinetic parameters such as AUC0-12, Cmax, Tmax, t1/2 and elimination rate constant were determined from plasma concentration-time profile for both formulations by a non-compartmental method. The statistical analysis of the data obtained in this study showed no significant difference between the tested OPZ products. The results indicated that the tested products have similar bioavailability profiles and therefore can be considered bioequivalent based on the obtained data of AUC, Cmax, and Tmax.

Open Access Original Research Article

Melatonin Improves Metabolic Abnormalities Induced by HAART in Mice

J. B. Borges, T. Sakurada Jr, L. Ciupa, A. R. T. Pupulin

Journal of Pharmaceutical Research International, Page 1-10
DOI: 10.9734/BJPR/2016/29474

Aims: Highly Active Antiretroviral Therapy (HAART) is associated with metabolic complications. An unexpected extension of functional implications of melatonin, the neuro-hormone synthetized during the night, has been reported on the development of type 2 diabetes, sleep disturbances and depression. Melatonin has been shown to reduce the toxicity and increase the efficacy of a large number of drugs.

Objective: Current study evaluated the effect of Melatonin on mice treated with antiretroviral therapy.

Materials and Methods: Animals were divided into experimental groups with 12 animals each: (I) animals treated with antiretroviral therapy for 15 days, (II) animals treated with antiretroviral therapy and melatonin 6 mg/kg/day for 15 days, (III) untreated animals. Body weight, water intake and ration, excretion products and behavior were clinically assessed before and after treatment; further, serum cholesterol, triglycerides, hepatic enzymes (AST, ALT, GGT), creatinine, were evaluated by specific methods. Results were analyzed with GraphPad Prism by Student´s t test.

Results: Animals treated with antiretroviral therapy and melatonin (II) had higher body weight gain, less hepatomegaly, less anxiety, lower levels of triglycerides, cholesterol and hepatic enzymes when compared to animals treated with antiretroviral therapy.

Conclusion: Due to the low toxicity of melatonin and its ability to reduce the side effects and increase the efficacy of drugs its use as a combination therapy with antiretroviral therapy seems important and worthy of pursuit.

Open Access Original Research Article

Anti-inflammatory Effects and Acute Toxicity of Methanol Stem Bark Extract of Morus mesozygia Stapf.

Kudirat O. Oshiomah, Oyinlade A. Odujoko, Abayomi M. Ajayi

Journal of Pharmaceutical Research International, Page 1-9
DOI: 10.9734/BJPR/2016/28746

Aim: Morus mesozygia is a specie of the Morus family in Africa that is traditionally used for the treatment of rheumatism. Until this moment, there is no available literature on the scientific evidence of the in vivo anti-inflammatory effects. The aim is to determine the safety of this extract after acute exposure and evaluate the anti-inflammatory effects in vitro and in vivo.

Methodology: The phytochemical screening of the powdered stem bark was determined following standard procedures. Extraction in methanol yielded a brownish extract, which was subjected to total phenolic and flavonoid contents estimation. Antioxidant activity was determined by DPPH free radical scavenging assay. Acute oral toxicity effects was evaluated in female mice and signs of toxicity was observed for 14 days. Anti-inflammatory activity was evaluated using the carrageenan-induced paw oedema and in vitro membrane stabilizing activity assay in rat erythrocytes.

Results: Preliminary phytochemical analysis revealed the presence of flavonoids, saponins, tannins, alkaloids, anthraquonones, and cardiac glycosides. Ratio of total phenolic to total flavonoid content was determined to be 0.53. MEMm showed strong antioxidant activity comparable to ascorbic acid in DPPH free radical scavenging activity assay. No signs of acute toxicity was observed indicating the LD50 is greater than 5000 mg/kg. MEMm (200 and 400 mg/kg) significantly (p < 0.05) reduced oedema formation in rat paw, and showed concentration dependent membrane stabilizing activities in rat erythrocytes.

Conclusion: The present study shows that stem bark methanol extract of Morus mesozygia is safe and contains bioactive constituents with antioxidant, anti-inflammatory and membrane stabilizing properties.

Open Access Original Research Article

Formulation Development and Optimization of Ibuprofen Poloxamer Melt Granules Using Hydrophilic Excipients

Bhavin Y. Gajera, Rohit P. Dugar, Rutesh H. Dave

Journal of Pharmaceutical Research International, Page 1-19
DOI: 10.9734/BJPR/2016/29048

The focus of this research work was to develop a melt granulation technique to enhance solubility, dissolution rate and associated flowability concerns of Ibuprofen. Hydrophilic excipients like xylitol and lactose anhydrous were added to the binary mixture of conventional low melting surfactant Poloxamer 407 and Ibuprofen. Physical mixtures of Ibuprofen and Poloxamer 407 were prepared in ratios of 1:0.25, 1:0.5 and 1:0.75 using a water-jacketed high shear mixer. For each ratio of Ibuprofen and Poloxamer 407, xylitol and lactose anhydrous were added separately at two levels (75 mg and 150 mg) per unit dose containing 200 mg drug. Phase solubility studies revealed linearity in drug solubility enhancement with Poloxamer 407 concentration. In vitro dissolution studies were carried out for drug, physical mixtures (PM) and melt granules (MG) for all ratios in de-ionized water and 0.1 N HCl (pH=1.2). Solid state characterization was performed using Fourier transform infrared spectroscopy (FTIR), modulated differential scanning calorimetry (mDSC) and powder X-ray diffraction (PXRD) methodologies. Powder rheology studies were performed conventionally by measuring Carr’s index and Hausner’s ratio. Basic flowability energy values were calculated using a powder rheometer to corroborate flowability data measured by conventional methods. Particle morphological studies were done by Scanning electron microscope (SEM) and Fluid imaging technologies. In-vitro dissolution studies showed approximately 7 fold drug release in water and 19 fold drug release in acidic media for MG 1:0.75 at hydrophilic excipient level of 150 mg compared to that of neat Ibuprofen in respective dissolution media. mDSC and PXRD data confirms crystalline nature of drug in the formulations. FTIR data confirms no interactions between drug and excipients used during processing. Particle morphology analysis confirms absence of rhombic Ibuprofen crystals in formulations. Dissolution rate and solubility enhancement was seen due to synergistic effects of Poloxamer 407 and hydrophilic excipients incorporated in formulations.

Open Access Original Research Article

HPLC, Densitometric and Visible-Spectrophotometric Determination of Triclabendazole and Ivermectin

Sawsan A. Abdel Razeq, Asmaa O. El Demerdash, Hoda F. El Sanabary

Journal of Pharmaceutical Research International, Page 1-14
DOI: 10.9734/BJPR/2016/29196

Two methods were developed for simultaneous determination of triclabendazole and ivermectin, in addition to a Vis-spectrophotometric method for the analysis of ivermectin only. The first one was HPLC method in which efficient separation of two drugs was achieved on a C18 column with isocratic elution and a mobile phase composed of acetonitrile-methanol-0.005M KH2PO4 in a ratio of (60:30:10, v/v/v), pH 6. The linearity range was found to be 2.5-50 µg mL-1 for triclabendazole and 1-20 µg mL-1 for ivermectin with mean accuracy of 100.11% ± 0.99 and 100.08% ± 0.53, respectively. The second method was a densitometric evaluation of thin-layer chromatograms of the two drugs using a mobile phase of chloroform-acetone (8: 2, v/v). The plates were visualized under UV lamp at 254 nm where spots appeared at Rf 0.79 and 0.33 for triclabendazole and ivermectin, respectively. The chromatograms of the two drugs were measured densitometrically at 306 nm in the range 2.5-25.0 µg/spot for triclabendazole and at 245 nm in the range of 0.5-5.0 µg/spot for ivermectin with mean accuracy of 100.38% ± 0.52 and 100.05% ± 0.41, respectively. The Vis-spectrophotometric method was applied for the determination of ivermectin depending on its reducing character on tetrazolium red to give highly colored red product absorbing maximally at 485 nm in the range of 10-200 µg mL-1 with mean accuracy of 100.61% ± 0.43. The first two methods provided selective recovery of triclabendazole and ivermectin (100.53% ± 0.97 and 100.03% ± 0.82, 99.94% ± 1.60 and 98.77% ± 0.72; respectively). While the third Vis-spectrophotometric method provided selective recovery of ivermectin (100.86% ± 0.93) in presence of triclabendazole. Successful application of the methods for analyzing triclabendazole and ivermectin in their pharmaceutical formulations was obtained. The validity of the method was evaluated in terms of linear regression analysis, precision, accuracy and selectivity.

Open Access Original Research Article

Evaluation of C. cassia Effectiveness in Behavioral Modulation of Haloperidol Induced Parkinson’s Disease (Mice Model)

Awais Ali Zaidi, Tanveer Ahmed Khan, Lubna Shakir, Mahtab Ahmad Khan, Muhammad Yousaf, Arsalan Ali, Atif Saeed, Zaka-Ur- Rehman, Atta-Ur- Rehman

Journal of Pharmaceutical Research International, Page 1-7
DOI: 10.9734/BJPR/2016/29286

Aims: This study was undertaken to evaluate the effectiveness of behavioral modulation of C. cassia extract against Haloperidol induced Parkinson’s disease (PD) in albino mice.

Study Design: The study used animal models to test the effect of Haloperidol in development of PD and effectiveness of C. cassia extract in behavioral modulation in mice before & after the treatment of PD.

Place and Duration of Study: Pharmacology Lab, Department of Pharmacology, Faculty of Pharmacy, Hajvery University, Lahore-Pakistan.

Methodology: The study was divided into three phases; During Phase I, all subjects were randomly divided into four groups comprising of 7 subjects each through flip of coin method and were trained for wire hanging test, grip strength test, Vertical rod test, and swim test for seven days. During Phase II, PD was induced by intraperitoneally administering 1 mg / kg / day of Haloperidol for 7 days. Animals of Group A (Normal) was served as control, Group B (Diseased, HP) received haloperidol (1 mg/kg / day), Group C (HP+CN-100), and Group D (HP+CN-200) were administered C. cassia extract, 100 mg and 200 mg per kg of body weight orally for 36 days respectively. During Phase III the above mentioned test were performed and effects of C. cassia extracts were recorded. The results of the present study revealed that dose of C. cassia extract 100 mg/kg is more safe and effective than 200 mg/kg. However, in swim test Group D (HP+CIN-200) is more statistically significant as compared to Group B (Diseased, HP) with P = .003.

Conclusion: The current study concludes that oral administration of C. cassia extract modulates haloperidol induced behavioral changes in mice. The present study suggests that extract will be helpful as adjunct therapy along with standard therapy of Levodopa/Carbidopa.