DARU Journal of Pharmaceutical Sciences
Year:2009 | Volume:17 | Issue:4|Papers Count:12

Dr.Sarbolouki was a distinguished Iranian Biophysics and Polymer Chemist who had numerous publications and patent on Dendrosome ( a DNA vehicle), Structural Biology, Biomaterials, Membranes and Chromatography. He was born in 1949 and obtained B.S degree in Chemistry from Tehran University in 1966 and Ph.D degree in Macromolecular Physical Chemistry from Polytechnic University of New York in 1972. He then spent two years at Michigan State University as a postdoctoral fellow before joining to NASA where he worked as a group leader until 1981.

Background and the purpose of the study: This investigation deals with risperidone cyclodextrin (CD) complexation for parenteral administration to improve its aqueous solubility which would be beneficial over immediate and sustained release formulations available in market especially for agitated and non-cooperative psychotic patients. Methods: The phase solubility study of the drug with b-CD, hydroxypropyl (HP)- b-CD and g-CD was conducted and CDs with higher stability constants were selected for complexation. The complexes of Risperidone with b-CD and HP-b-CD were prepared by precipitation and vacuum drying methods, respectively. Fourier transform-infrared, X-ray diffraction and differential scanning calorimetry techniques were used for characterization of complexes. Drug precipitation study of complex’s solution in water for injection and 100 ml of 0.1 M pH 7.4 phosphate buffer saline and stability study in accelerated condition were also carried out.Results: The stability constants of the CD were in the following order: b-CD (341.953±11.87 M-1) > HP-b-CD (170.817± 5.93 M-1) > g-CD (93.716 ± 3.25 M-1). CDs with high stability constants were selected to prepare the drug CD complex. The complexation efficiencies of b-CD and HP-b-CD were 95.23 ± 2.27% and 97.59 ±1.97%, respectively. Both types of CDs exhibited complexation at 1:2 molar stoichiometric ratio. The drug precipitation study indicated complete solubility (100% drug dissolution) without a trace of precipitate within 5 mins. The complexes were found to be stable for a period of 3 months under accelerated stability conditions. Major conclusion: Stable complexes of risperidone were successfully formulated using both b-CD and HP-b-CD by simple and highly efficient methods of complexation for parenteral administration.

Background and the Purpose of the study: The purpose of the study was formulate and systemsystematic evaluation in-vitro and in-vivo behaviour of Glipizide mucoadhesive microspheres using 32 full factorial design.  Methods: Concentration of Polycarbophil and Sodium Alginate were selected as independent variables and the effects were checked on dependent variables like swelling index, mucoadhesion, drug entrapment efficiency and T75. In vivo studies were also performed to determine hypoglycemic activity of the mucoadhesive microspheres. Results: The best batch exhibited drug entrapment efficiency of 75%, swelling index of 1.8 and mucoadhesion was 100%. The drug release from the microspheres was also sustained for more than 9 hrs.  Conclusion: The concentration of polycarbophil and sodium alginate had highly significant effects on dependent variables. In-vivo testing demonstrated a significant hypoglycemic effect of glipizide.

Background and the purpose of the study: Pharmacokinetic parameters of tramadol and its three metabolites in plasma, saliva and urine following administration of 100 mg single oral dose were investigated in 24 healthy volunteers.Materials and Methods: 12 male and 12 female healthy volunteers received a single oral dose of tramadol and Plasma, mixed saliva -secreted samples without any stimulation and urine were analyzed for Tramadol and its main metabolites by HPLC method.Results and Disscusion: Almost 16.2% of tramadol and 11.2, 1.1 and 5.0% of O-desmethyltramadol (M1), N-desmethyltramadol (M2) and N,O-didesmethyltramadol (M5) respectively were recovered in 30 hrs collected urine. Renal clearance of tramadol, M1, M2 and M5 were 114.7 ± 44.5, 193.9 ± 67.6, 116.1 ± 61.8 and 252.0±91.5 (mL/min) respectively. The maximum plasma concentration of tramadol, M1, M2 and M5 were 349.3 ± 76.7, 88.7±30.3, 23.1 ±11.4 and 30.0 ± 11.7 (ng/mL) at 1.6 ± 0.4, 2.4 ± 0.7, 2.8 ± 1.0 and 2.7 ± 1.4 hrs after drug administration respectively. Tramadol and its metabolites appeared in a significant amount in saliva with the saliva/plasma ratios of 9.0, 1.6, 12.3 and 2.8 for tramadol, M1, M2 and M5 according to AUC(0-24) respectively. Conclusion: Conclusion Strong correlations were found between plasma and saliva concentrations for all studied compounds and a dissection to pre and post absorption components improved these correlations. Results o f this study suggests that saliva is a suitable alternative to plasma for clinical and toxicological studies of tramadol and in addition to passive diffusion, a possible active transport is also suggested to describe the elevated saliva/plasma ratios for these compounds.

Background and purpose of the study. 3(2H)-Isothiazolones have shown antimicrobial activity and have been used as preservative in different products. However, reports on their structure-antimicrobial activity relationship are scanty. The aim of this study was to determine the relationship between lipophilicity and antimicrobial activity of several 2- (4-substituted phenyl) -3(2H)-isothiazolones of which some have shown antibacterial activities similar or higher than gentamycin, ceftazidime, ceftriaxone, ciprofloxacin , and antifungal activites similar or higher than itraconazole and ketoconazole as reference drugs.Methods. Partition coefficient (log Po/w) of the tested compounds was determined experimentally by a reversed- phase high performance liquid chromatography method using octadecyl-poly(vinyl alcohol) (ODP) column and methanol-water gradient as mobile phase and theoretically by Clog P and ALOGPS computer programs. Results. The HPLC and theoretical log Po/wvalues showed potential correlations which indicate that both experimental and theoretical methods are equally suitable to predict lipophilicity of 3(2H)-isothiazolones. There were also significant correlations between MICs (minimum inhibitory concentrations) of 5-chloro substituted 3(2H)- isothiazolnes against Salmonella typhimurium and Escherichia coli and experimentally determined log Po/w values, as well as MICs of 5-unsubstituted 3(2H)- isothiazolnes against E. coli and ALOGPS values. The antifungal activity of the tested compounds against Tricophyton. mentagrophytes and M.canis increased with increase in the experimental and theoretical log P values , but this increase was only significant for the activity against Microsporum. canis.v

Background and the Purpose of the Study: The aim of this study was development and validation of a simple, rapid and sensitive spectrofluorimetric method for determination of total flavonoids in two topical formulations of Calendula officinalis, Ziziphus Spina-christi and an oral drop of Hypiran perforatum L. The proposed method is based on the formation of terbium (Tb3+)-flavonoids (quercetin as a reference standard) complex at pH 7.0, which has fluorescence intensely with maximum emission at 545 nm when excited at 310 nm. Method: For ointments masses of topical formulations were weighed and added to ethanol-aqueous buffer (pH 10.0) and the resulting mixtures were shaken and then two phases were separated by centrifugation. Aqueous phases were filtered and then diluted with water. For Hypiran drops an appropriate portion was diluted with ethanol and then aliquots of sample or standard solutions were determined according to the experimental procedure.Results: Under the optimum conditions, total concentrations of flavonoids (as quercetin equivalent) in three tested formulations were found to be 0.204 mg/g (for Dermatin cream), 0.476 mg/g (for Calendula ointment) and 13.50mg/ml (for Hypiran drops). Analytical recoveries from samples spiked with different amounts of quercetin were 96.1-104.0 % with RSD % of less than 3.5.Conclusion: The proposed method which requires a simple dissolution step without any matrix interferences provided high sensitivity and selectivity and was easily applied to determine total flavonoids in real samples of three investigated formulations with excellent reproducibility.

Background and the purpose of the study: The use of highly sulfated cyclodextrins (HS-CDs) as chiral selectors in capillary electrophoresis (CE) has been examined for rapid and reproducible enantioseparation of the model drug amlodipine, a calcium channel blocker. Materials and Methods: Fused silica capillaries with an inner diameter of 50 mm, and a total length of 45.5 cm (8.5 cm to the detector) were used. Capillaries were rinsed with polyethylene oxide (PEO) once daily. A systematic method development approach was conducted by modifying selected parameters such as the type and concentration of the chiral selector, the buffer pH and concentration of the background electrolyte.Results: Baseline separation was achieved at low (i.e. 0.05%w/v) concentrations of HS-aCD, but migration time and peak area repeatability were more than 4% and 25% of the relative standard deviation (RSD), respectively. At higher concentrations (>0.3%) of HS-aCD, amlodipine was transported to the anode by the carrier ability of HS-aCD. In carrier mode, the migration order of enantiomers was reversed, the migration time was reduced and the peak area repeatability of analysis was improved. The optimum electrophoretic conditions for the stereoselective analysis of amlodipine were obtained in carrier mode with 25 mM sodium phosphate buffer containing 1.25% w/v of HS-aCD at pH 2.5 with an applied voltage of +15 kV. Under these conditions migration time was less than 3 min and within-day migration time and peak area repeatability, were less than 0.4% and 2.1% RSD, respectively. Conclusions: Rapid enantioseparation was achieved with minimum variation in quantitative analysis. These optimized conditions are appropriate for the enantioselective analysis of amlodipine.

Background and the purpose of the study: Following the phase I clinical trial of the herbal drug IMOD™ in HIV/AIDS patients, further studies were required to assess the drug efficacy and side effects. Therefore its safety and efficacy in HIV infected patients in a phase II were examined, and clinical trial phase III were designed. Methods: This study was conducted in three stages. In the first stage six patients who were resistant to highly active anti retroviral therapy (HAART) regimen were chosen and offered therapy with Setarud. Subsequently another group of 27 patients with CD4 count less than 350 but without AIDS defining criteria were enrolled to the study and randomly assigned to intervention. In the third stage a double-center randomized clinical trial was conducted at two independent research centers and universities of Iran. Seventy patients were recruited and randomly allocated into groups, called “control” and Setarud groups, using a balanced block randomization method. The main outcome measure was CD4 count. Patients were observed and thoroughly examined (Clinical and laboratory) for six months. Results: In stages I and II, the mean CD4 count gradually increased within 3 and 6 months intervals. In the stage III the baseline of CD4 counts and other characteristics between two groups were quite similar. The mean increase in CD4 count in Setarud group was about 2-3 fold higher than controls. This effect was much more pronounced in a subgroup of patients with a baseline CD4 count of 200-400 (168 vs. 65, 203 vs. 58, 299 vs. 143 and 285 vs. 109, for time intervals of follow-up, respectively) (p<0.001).Conclusion: There was a significant improvement in the immune system of HIV patients receiving Setarud therapy by increase in the CD4 count to the higher and more protective level in most subjects. Considering results of the safety tests and reports of the durability of the Setarud effects the use this drug in HIV patients, especially at the pre-AIDS period, as a therapeutic vaccine to slow down the progression of the disease, is recommended.

Background and the purpose of the study: This study was designed to evaluate the effectiveness of different concentrations of Nanosilver solution against Iranian strain of Leishmania major (MRHO/IR/75/ER) both in vitro and in vivo on BALB/c mice model for the first time. Methods: this is an interventional study which was conducted on the infected macrophages by L. major amastigotes in vitro. In order to confirm the in vitro results, various concentration of Nanosilver solution were administered topically on skin lesions caused by L.major in 78 inbred BALB/c mice as test or interventional and 52 mice as control groups once or twice daily for 14 days.Results and major conclusion: Results of this study showed that different concentration of Nanosilver reduced proliferation of L. major amastigotes compared with the control wells but the differences were not statistically significant. Also, different concentrations of Nanosilver did not decrease the lesion sizes and amastigote counts in the BALB/c mice significantly. Secondary infection was significantly decreased in Nanosilver- treated groups compared with control groups (p<0.01). In conclusion, Nanosilver seems to be effective for control of secondary infection of localized cutaneous leishmaniasis.

Background and propose of the study: As there is no significant work on O. persica, a phytochemical investigation of this species was carried out in this study. Methods: The structures of the compounds 1-4 were established by their spectral data and their relative configuration was determined by 2D NMR. Results and major conclusion: Four known diterpenoids belonging to the clerodane and tetracyclic diterpene types were isolated for the first time from Otostegia persica (Burm.) Boiss. These compounds are known to occur only in genus Otostegia.

Background: Current treatment of hemophilia which is one of the most common bleeding disorders, involves replacement therapy using concentrates of FVIII and FIX .However, these concentrates have been associated with viral infections and thromboembolic complications and development of antibodies. The use of recombinant human factor VII (rhFVII) is effective for the treatment of patients with hemophilia A or B, who develop antibodies ( referred as inhibitors) against replacement therapy, because it induces coagulation independent of FVIII and FIX. However, its short half-life and high cost have limited its use. One potential solution to this problem may be the use of FVIIa gene transfer, which would attain continuing therapeutic levels of expression from a single injection. The aim of this study was to engineer a novel hFVII (human FVII) gene containing a cleavage site for the intracellular protease and furin, by PCR mutagenesis.Methods: The sequence encoding light and heavy chains of hFVII, were amplified by using hFVII/pTZ57R and specific primers, separately. The PCR products were cloned in pTZ57R vector. Results and discussion: Cloning was confirmed by restriction analysis or PCR amplification using specific primers and plasmid universal primers. Mutagenesis of sequence encoding light and heavy chain was confirmed by restriction enzyme.Conclusion: In the present study, it was provided recombinant plasmids based on mutant form of DNA encoding light and heavy chains. Joining mutant form of DNA encoding light chain with mutant heavy chain led to a new variant of hFVII. This variant can be activated by furin and an increase in the proportion of activated form of FVII. This mutant form of hFVII may be used for gene therapy of hemophilia.

Introduction: The human EP1 (hEP1) prostanoid receptor is a G-Protein Coupled Receptor (GPCR) which plays important physiological roles in some systems in the body like cardiovascular and immune systems and could be a very important target for drug design.Materials and methods: To understand the molecular structure of hEP1 receptor, a homology model of the receptor was constructed from the 2.4 Å resolution crystal structure of human b2-adrenergic receptor (PDB code: 2RH1), using three different sequence alignments. The model including PGE2 inside the active site was subjected to molecular dynamics simulation. Docking studies were performed for PGE2 and 10 prostanoid analogs in the active site of the modeled receptor. Results and Discussion: The structure of modeled receptor remained stable during the 10 nanosecond(ns) simulation. In the docking simulations a correlation of r2=0.74 was observed between the Ki values and the docking scores of the prostanoid compounds. The structure which was modeled in the present study can be used in the structure-based drug design, helping the rational design of novel ligands for the hEP1 receptor.