فهرست مطالب

DARU, Journal of Pharmaceutical Sciences - Volume:18 Issue: 3, Autumn 2010

DARU, Journal of Pharmaceutical Sciences
Volume:18 Issue: 3, Autumn 2010

  • تاریخ انتشار: 1389/07/05
  • تعداد عناوین: 12
|
  • T. Binesh Marvasti, Kh Adeli Page 146
    Obesity epidemic has been spread all over the world in the past few decades and has caused a major public health concern due to its increasing global prevalence. Obese individuals are at higher risks of developing dyslipidemic characteristics resulting in increased triglyceride and LDL-cholesterol content and reduced HDL-cholesterol levels. This disorder has profound implications as afflicted individuals have been demonstrated to be at increased risk of development of hypertension, atherosclerosis, type 2 diabetes and cardiovascular diseases. Today, this phenotype is designated as metabolic syndrome. According to the criteria set by the International Diabetes Federation (IDF), for a patient to be diagnosed with metabolic syndrome, the person must have central obesity plus any two of the following conditions: raised TG, reduced HDL-cholesterol, raised blood pressure, and increased fasting plasma glucose. Current National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines for the treatment of patients with the metabolic syndrome encourage therapies that lower LDL cholesterol and TG and raise HDL-cholesterol. Primary intervention often involves treatment with statins to improve the lipid profiles of these patients. However, recent studies suggest the potential of newly identified drugs including thiazolidinediones, GLP-1 agonists, and DPP-4 inhibitors that seem to be promising in reducing the level of progression of metabolic syndrome related disorders. This review discusses the current pharmacological treatments of the metabolic syndrome with the above mentioned drugs.
  • H. Hamishehkar, M.T. Beigmohammadi, M. Abdollahi, A. Ahmadi, A. Mahmoodpour, M.R. Mirjalili, R. Abrishami, M.R. Khoshayand, K. Eslami, M. Kanani, M. Baeeri, M. Mojtahedzadeh Page 155
    Background and the purpose of the study: sepsis is one of the most widespread and lethal disease in Intensive Care Units (ICU). Based on pathophisyology of sepsis, it seems that routine laboratory tests combined with analysis of pro-inflammatory cytokines plasma levels, help clinicians to have more information about disease progress and its correct management.
    Methods
    This was a prospective observational study to determine the predictive role of Tumor Necrosis Factor alpha (TNF-α), Interleukin (IL)-1β and IL-6 as three main pro-inflammatory cytokines and Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment (SOFA) as two scoring systems in mortality of critically ill patients with severe sepsis. Fifty and five patients with criteria of severe sepsis were included in this study. An exclusion criterion was post Cardiopulmonary Resuscitation (CPR) status. Cytokines (TNF-α, IL-1β and IL-6) were assayed in the first, third and seventh days in blood of patients.Results and major
    Conclusion
    Among three measured cytokines, sequential levels of TNF-α and IL-6 showed significant differences between survivors and nonsurvivors. IL-6 had a good correlation with outcome and scoring systems during the period of this study. The areas under the receiver operating characteristic (AUROC) curve indicated that APACHE II (0.858, 0.848, 0.861) and IL-6 (0.797, 0.799, 0.899) had discriminative power in prediction of mortality during sequental measured days. Multiple logestic regression analysis identified that evaluation of APACHE II and TNF-α in the first day and APACHE II and IL-6 in the third and seventh days of severe septic patients are independent outcome predictors. Results of this study suggest that IL-6 and APACHE II are useful cytokine and scoring systems respectively in prediction of mortality and clinical evaluation of severe septic patients.
  • S. Barezi, N. Fahham, M. Seyedabadi, S.N. Ostad, M.H. Ghahremani Page 163
    Background and the purpose of the study:Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) is involved in inflammation, apoptosis/survival and tumorigenesis as well as resistance to chemotherapy. NAG-1 protein is synthesized as pro-peptide, cleaved and secreted as mature protein. Regulation of NAG-1 is not completely discovered and increased level of NAG-1 has been reported in many cancers. The expression of NAG-1 in cancer cells could affect the progression of tumor growth. In addition the secretion of full length and mature forms of NAG-1 can influence cell proliferation in other cells. In this study the role of full length and mature forms of NAG-1 on viability of HT-1080 and MCF-7 cells were evaluated, and the cytotoxicity of celecoxib, indomethacin, tamoxifen and doxorubicin in HT1080 cells stably expressing NAG-1 were also tested.
    Methods
    Full length and mature NAG-1 was cloned from cDNA library of HCT116 cells and stably transfected in HT1080 cells. Cells were treated with different concentrations of indomethacin, celecoxib, tamoxifen and doxorubicin and viability was assessed by MTT assay. The effect of conditioned medium of NAG-1 expressing cells on proliferation of MCF-7 and HT1080 cells were also tested.
    Results
    The growth curves of HT1080 cells expressing full length and mature NAG-1 were not different. The viability of HT1080 cells expressing NAG-1 in the presence of indomethacin, doxorubicin and tamoxifen compared to untransfected cells was higher. The proliferation of HT1080 and MCF-7 cells were inhibited by conditioned medium of NAG-1 expressing cells in 24 and 48 hrs.Major
    Conclusion
    NAG-1 expression enhances drug resistance to tamoxifen, indomethacin and doxorubicin in HT1080. In addition, condition medium of NAG-1 expression cells inhibits proliferation in MCF-7 and HT1080 cells. Thus, NAG-1 expression can induce drug resistance in NAG-1 expressing cells and inhibition of viability in non expressing cells. Thus, NAG-1 is suggested as a marker for effective cancer chemotherapy and tumor progression.
  • S. Kheybari, N. Samadi, S.V. Hosseini, A. Fazeli, M.R. Fazeli Page 168
    Background and the purpose of the study:The most prominent nanoparticles for medical uses are nanosilver particles which are famous for their high anti-microbial activity. Silver ion has been known as a metal ion that exhibit anti-mold, anti-microbial and anti-algal properties for a long time. In particular, it is widely used as silver nitrate aqueous solution which has disinfecting and sterilizing actions. The purpose of this study was to evaluate the antimicrobial activity as well as physical properties of the silver nanoparticles prepared by chemical reduction method.
    Methods
    Silver nanoparticles (NPs) were prepared by reduction of silver nitrate in the presence of a reducing agent and also poly [N-vinylpyrolidone] (PVP) as a stabilizer. Two kinds of NPs were synthesized by ethylene glycol (EG) and glucose as reducing agent. The nanostructure and particle size of silver NPs were confirmed by scanning electron microscopy (SEM) and laser particle analyzer (LPA). The formations of the silver NPs were monitored using ultraviolet-visible spectroscopy. The anti-bacterial activity of silver NPs were assessed by determination of their minimum inhibitory concentrations (MIC) against the Gram positive (Staphylococcus aureus and Staphylococcus epidermidis) as well as Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. Results and
    Conclusion
    The silver nanoparticles were spherical with particle size between 10 to 250 nm. Analysis of the theoretical (Mie light scattering theory) and experimental results showed that the silver NPs in colloidal solution had a diameter of approximately 50 nm.Both colloidal silver NPs showed high anti-bacterial activity against Gram positive and Gram negative bacteria. Glucose nanosilver colloids showed a shorter killing time against most of the tested bacteria which could be due to their nanostructures and uniform size distribution patterns.
  • M. Ansari, Kh Rafiee, N. Yasa, S. Vardasbi, S.M. Naimi, A. Nowrouzi Page 173
    Background and the purpose of the study:Melatonin has recently been found in several plant tissues. Some reports show that the majority of the herbs containing the high level of melatonin have been used traditionally to treat neurological disorders or diseases associated with the generation of free radicals. Current study was undertaken to screen some medicinal plant species with historical evidence of efficacy in the treatment of neurological and antioxidant deficiency related disorders for their melatonin content. The melatonin content of boiled and alcoholic extracts were also compared.
    Methods
    In this study, three medicinal herbs, Tanacetum parthenium (L.) Schultz. Bip. (Asteraceae), Tripleurospermum disciforme (C.A.Mey) Schultz. Bip. (Asteraceae) and Viola odorata (L.) (Violaceae) were analyzed using high performance liquid chromatography with ultraviolet detector (HPLC-UV), enzyme linked immunosorbent assay (ELISA) and thin layer chromatography (TLC).
    Results
    Melatonin content in the dry plant powders differed with different assay methods (p < 0.001). For example, the melatonin content in T. disciforme was determined as 3.073 μg/g and 2.906 μg/g by the HPLC and the ELISA methods, respectively.Major
    Conclusion
    The results demonstrated that a hydroalcoholic solution could extract more melatonin from flowers of the herbs than hot water (p < 0.001). The presence of melatonin in these plant tissues may provide some explanation for the anecdotal evidence of their physiological effects in humans.
  • F. Rasoulzadeh, D. Asgari, A. Naseri, M.R. Rashidi Page 179
    Background and the purpose of the study: The binding ability of a drug to serum albumin has influence on the pharmacokinetics of a drug. In the present study, the mutual interaction of anticancer drug erlotinib hydrochloride with bovine serum albumin (BSA) using fluorescence and UV/vis spectroscopy was investigated.
    Methods
    The BSA solution (0.1 mM) was prepared daily in Tris buffer (0.05 mol l-1, pH =7.4) and treated at final concentration of 1.67×10-5 M with different amounts of erlotinib hydrochloride to obtain final concentrations of 0, 0.2, 0.4, 0.8, 1, 2, 4, 6, 8, 20 and 42 μM receptively. The mixture was allowed to stand for 5 min and the fluorescence quenching spectra were recorded at 298, 303, 308 and 313 K.
    Results
    It was found that erlotinib hydrochloride caused the fluorescence quenching of BSA by the formation of a BSA-erlotinib hydrochloride complex. The mechanism of the complex formation was then analyzed by determination of the number of binding sites, apparent binding constant Ka, and calculation of the corresponding thermodynamic parameters such as the free energy (ΔG), enthalpy (ΔH) and entropy changes (ΔS) at different temperatures. Results showed that binding of erlotinib hydrochloride to BSA was spontaneous, and the hydrophobic forces played a major role in the complex formation. The distance, r, between donor (BSA) and acceptor (erlotinib hydrochloride) was found to be less than 8 nm suggesting the occurrence of non-radiative energy transferring and static quenching between these two molecules.
    Conclusion
    The results provided preliminary information on the binding of erlotinib hydrochloride to BSA and the presence of a single binding site on BSA and Ka values for the association of BSA with erlotinib hydrochloride increased by the increase in temperature.
  • A. Rezaei Mokarram, A. Kebriaee Zadeh, M. Keshavarz, A. Ahmadi, B. Mohtat Page 185
    Background and the purpose of the study: During the last two decades one of the most important problems in drug formulations has been low aqueous solubility of new molecules. However, numerous techniques, such as milling, co-solvent solubilization and solid dispersion have been used conventionally for aqueous solubility enhancement and the rate of solubility. Recently, nanoparticle engineering processes have been developed and reported for pharmaceutical applications to increase the dissolution rate of low-soluble drugs which in turn may leads to substantial increases in bioavailability. In this study, a controlled precipitation method was used to produce indomethacin nano-solid suspension in a polymeric matrix (as a model), in order to increase the solubility and rate of the dissolution of poorly soluble model drug.
    Methods
    Nano-solid suspension of indomethacin in polyvinyl pyrrolidine (PVP) was prepared by controlled precipitation technique, characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and evaluated for in vitro solubility and dissolution rate.Results and major
    Conclusion
    Absence of thermal and diffractional peaks in DSC and XRD studies indicated that indomethacin interacts with PVP in solid phase. The solubility of indomethacin in nano-solid suspension compared to crystalline form was increased to about four-fold. It was found that particle size distribution depend to the polymer MW and drug: polymer ratios. Spectroscopy methods and Transmission Electron Microscopy (TEM) images showed that indomethacin dispersed as amorphous nanosize particles in freeze dried powder. Enhanced solubility and dissolution rate of indomethacin compared to physical mixtures and crystalline form of indomethacin (polymorph I), demonstrated that it interacts with PVP via hydrogen bond and probably forming eutectic mixture.
  • J. Emami Page 193
    Background and the purpose of the study:The relative in vivo bioavailability and in vitro dissolution studies of three chemically equivalent amiodarone generic products in healthy volunteers was evaluated in three separate occasions. The possibility of a correlation between in vitro and in vivo performances of these tablet formulations was also evaluated.
    Methods
    The bioequivalence studies were conducted based on a single dose, two-sequence, cross over randomized design. The bioavailability was compared using AUC0-72, AUC0-∞, Cmax and Tmax. Similarity factor, dissolution efficiency (DE), and mean dissolution time (MDT) was used to compare the dissolution profiles. Polynomial linear correlation models were tested using either MDT vs mean residence time (MRT) or fraction of the drug dissolved (FRD) vs fraction of the drug absorbed (FRA).
    Results
    Significant differences were found in the dissolution performances of the tested formulations and therefore they were included in the development of the correlation. The 90% confidence intervals of the log-transformed AUC0-72, AUC0-∞, and Cmax of each two formulations in each bioequivalence studies were within the acceptable range of 80-125%. Differences were not observed between the untransformed Tmax values. Poor correlation was found between MRT and MDT of the products. A point-to-point correlation which is essential for a reliable correlation was not obtained between pooled FRD and FRA. The dissolution condition which was used for amiodarone tablets failed for formulations which were bioequivalent in vivo and significant difference between the dissolution characteristics of products (f2<50) did not reflect their in vivo properties.Major
    Conclusions
    Bioequivalence studies should be considered as the only acceptable way to ensure the interchangeability and in vivo equivalence of amiodarone generic drug products. The dissolution conditions used of the present study could be used for routine and in-process quality control of amiodarone tablet formulations.
  • N. Vishal Gupta, H.G. Shivakumar Page 200
    Background and the purpose of the study: Many drugs which have narrow therapeutic window and are absorbed mainly in stomach have been developed as gastroretentive delivery system. Rosiglitazone maleate, an anti-diabetic, is highly unstable at basic pH and is extensively absorbed from the stomach. Hence there is a need to develop a gastroretentive system. In this study a superporous hydrogel was developed as a gastroretentive drug delivery system.
    Methods
    Chitosan/poly(vinyl alcohol) interpenetrating polymer network type superporous hydrogels were prepared using a gas foaming method employing glyoxal as the crosslinking agent for Rosiglitazone maleate. Sodium bicarbonate was applied as a foaming agent to introduce the porous structure. Swelling behaviors of superporous hydrogel in acidic solution were studied to investigate their applications for gastric retention device. The optimum preparation condition of superporous hydrogels was obtained from the gelation kinetics. FT-IR, scanning electron microscopy, porosity and swelling ratio studies were used to characterize these polymers. In vitro drug release studies were also carried out.
    Results
    The introduction of a small amount of Poly(Vinyl Alcohol) enhanced the mechanical strength but slightly reduced the swelling ratio. The prepared superporous hydrogels were highly sensitive to pH of swelling media, and showed reversible swelling and de-swelling behaviors maintaining their mechanical stability. The degradation kinetics in simulated gastric fluid showed that it had biodegradability. Swelling was dependent on the amount of chitosan and crosslinker. The drug release from superporous hydrogels was sustained for 6 hrs.Major
    Conclusion
    The studies showed that chitosan-based superporous hydrogels could be used as a gastroretentive drug delivery system for rosiglitazone maleate in view of their swelling and prolonged drug release characteristics in acidic pH.
  • J. Kawadkar, K. Chauhan Meenakshi, A. Ram Page 211
    Background and the purpose of the study:Pectin derivatives have been utilized for colonic drug delivery (CDD). In this study the effects of different formulation variables upon the characteristics of pectinate microparticles (MPs) prepared by ionotropic gelation technique for colonic delivery of mesalazine was investigated.
    Methods
    In-vitro drug release of MPs was studied using USP XXIV dissolution apparatus type I, in different fluids e.g. simulated gastric fluid (SGF: pH 1.2), simulated intestinal fluid (SIF: pH 7.4), and simulated colonic fluid (SCF: pH 6.8) of volume 900 ml, at 100 rpm maintained at 37 ± 0.2 °C. This study was also performed in the presence of 4% w/v rat caecal content (RCC) using phosphate buffer saline (pH 6.8) as SCF. Gamma scintigraphy study was performed on New Zealand rabbit animal model using 99m Tc.
    Results
    The results showed that maximum entrapment of mesalazine (86.1 ± 1.7 %) and strength of gel network zinc pectinate gel microparticles (ZPGD2) was achieved in cross-linking solution of pH 1.6. Batch of ZPGD2 showed least swelling ratio and drug release. In RCC medium the t50% value of CPG-MPs was 3-4 folds greater than ZPG-MPs. Scintigram showed the residence of ZPG-MPs (filled in enteric coated capsule) in colon more than 9 hrs and delivery of almost all the drug loading dose in colon.Major
    Conclusion
    The results of this study suggest the designed formulation of ZPG-MPs has the potential to serve as a colonic drug delivery system.
  • S.K. Madishetti, C.R. Palem, R. Gannu, R.P. Thatipamula, P.K. Panakanti, M.R. Yamsani Page 221
    Background and the purpose of the study: Domperidone (DOM) is a dopamine- receptor (D2) antagonist, which is widely used in the treatment of motion-sickness. The pharmacokinetic parameters make DOM a suitable candidate for transdermal delivery. The purpose of the present investigation was to develop transdermal delivery systems for DOM and to evaluate their physicochemical characteristics, in vitro release an ex vivo permeation through rat abdominal skin and their mechanical properties.
    Methods
    Bilayered matrix type transdermal drug delivery systems (TDDS) of DOM were prepared by film casting technique using hydroxypropyl methyl cellulose as primary and Eudragit RL 100 as secondary layers. Brij-35 was incorporated as a solubilizer, d-limonene and propylene glycol were employed as permeation enhancer and plasticizer respectively. The prepared TDDS were extensively evaluated for in vitro release, moisture absorption, moisture content, water vapor transmission, ex vivo permeation through rat abdominal skin, mechanical properties and stability studies. The physicochemical interaction between DOM and polymers were investigated by Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR).
    Results
    All the formulations exhibited satisfactory physicochemical and mechanical characteristics. The optimized formulation F6 showed maximum cumulative percentage of drug release (90.7%), permeation (6806.64 μg) in 24 hrs, flux (86.02 μg /hr/cm2) and permeation coefficient of 0.86x10-2 cm/hr. Values of tensile strength (4.34 kg/mm2) and elastic modulus (5.89 kg/cm2) revealed that formulation F6 was strong but not brittle. DSC and FTIR studies showed no evidence of interaction between the drug and polymers. A shelf life of 2 years is predicted for the TDDS.
    Conclusions
    Domperidone bilayered matrix type transdermal therapeutic systems could be prepared with the required flux and suitable mechanical properties.
  • N.M. Bhatia, K.R. Mahadik Bhatia Page 230
    Background and the purpose of the study: Various compounds from natural and synthetic origins containing the 1,3-diarylpropenone structure have been reported to produce a variety of biological activities like anti-microbial, anti-inflammatory, vascular muscle relaxant, etc. A systematic analysis of the structural features responsible for anti-inflammatory activity and a possible mode of their actions were proposed to be evaluated by synthesizing a set of compounds, screening them for anti-inflammatory activity and developing a QSAR model.
    Methods
    Two types of 1,3-diarylpropenone derivatives were synthesized employing the Claisen-Schmidt condensation. These compounds were then screened for their in vivo anti-inflammatory activity by the carrageenin induced rat paw edema method and also for in vitro cyclooxygenase-2 (COX-2) inhibition activity using a colorimetric kit for COX (ovine) inhibitor screening assay. These derivatives and their anti-inflammatory activity data were employed for QSAR analysis on Vlife MDS 3.5 software. The molecules were divided into training and test sets based on observed activity and QSAR models were generated for the training set and validated. The activity of the molecules of the test set was predicted according to the QSAR equation fit. Possible correlation between observed anti-inflammatory activity and in vitro cyclooxygenase-2 inhibition was also studied.Results and
    Conclusion
    Insignificant difference between the observed and predicted biological activity revealed that the selected electronic, steric and lipophilic parameters have a significant correlation (r2 = 0.85) with anti-inflammatory activity of the selected class of compounds. On the basis of results it may be suggested that the 1,3-diaryl-2-propen-1-ones framework is an attractive template for structural optimization to achieve better potency of anti-inflammatory activity. Similarly, the relatively low correlation between anti-inflammatory activity and cyclooxygenase-2 inhibition indicates that other modes of actions may also be responsible for the anti-inflammatory activity of the tested compounds.