Iranian Journal of Pharmaceutical Research
Volume:8 Issue: 1, Winter 2009

The aim of this study was to investigate the rheological behavior and mucoadhesive nature of saliva substitutes, by incorporating various mucoadhesive polymers into an artificial saliva pump spray formulation. For this purpose various mucoadhesive polymers including cellulosic polymers in the range of 0.1-1.0% and Carbomers such as C974p, C971, C934p and C971 in the range of 0.01-0.1% were added to a formulated aqueous-based artificial saliva pump spray formulation, containing fixed amounts of some essential electrolytes. The pH of the formulations was between 6.3-7.4. The formulations were examined in terms of appearance, taste, odor, spray-ability, short-term thermal and mechanical stability, pH, viscosity and rheological behavior, particle size distribution, as well as invitro mucoadhesive strength (MS). The mucoadhesivity ratio (MR) was also calculated as follows: MR=MStest/MScontrol, using natural saliva as the control. Natural saliva showed a pseudoplastic rheological behavior, with a viscosity in the range of 12.85-28.15cP. Hence, artificial saliva samples having viscosities within this range were selected. The rheological behavior and viscosity of the test samples as well as the natural saliva were subsequently determined. Similar to that found for the natural saliva, all the prepared formulations showed a pseudoplastic rheological behavior. Among the polymers, C974p had the highest viscosity (25.97±0.11 cP) and mucoadhesive strength (34.84±0.21 mN/cm2) followed by hydroxypropylmethylcellulose which had a viscosity of 25.48±0.11 cP and a mucoadhesive strength of 34.03±0.24 mN/cm2. Furthermore, the mucoadhesivity of C974p containing artificial saliva was 1.186 times greater than natural saliva and 1.387 times more than water. In conclusion, it seems that the presence of mucoadhesive polymers within the artificial saliva pump spray formulations could help to improve the adhesive nature of the formulation to mucosal surfaces, making it even more effective than the natural saliva.

This study was performed to design bilayer regioselective floating tablets of atenolol and lovastatin to give immediate release of lovastatin and sustained release of atenolol. Bilayer floating tablets comprised two layers, i.e immediate release and controlled release layers. The immediate release layer comprised sodium starch glycollate as a super disintegrant and the sustained release layer comprised HPMC K100M and xanthan gum as the release retarding polymers. Sodium bicarbonate was used as a gas generating agent. Direct compression method was used for formulation of the bilayer tablets. Accelerated stability studies were carried out on the prepared tablets inaccordance with ICH guidelines. Roentgenography was carried out to study the in vivo buoyancy of the optimized formulation. All formulations floated for more than 12 h. More than 90% of lovastatin was released within 30 min. HPMC K100M and xanthan gum sustained retarded the release of atenolol from the controlled release layer for 12 h. After stability tests, degradation of both drugs were found but the drugs, contents were found to be within the range. Diffusion exponents (n) were determined for all the formulations (0.53-0.59). The release of atenolol was found to follow a mixed pattern of Korsmeyer-Peppas, Hixson-Crowell and zero order release models. The optimized formulation was found to be buoyant for 8 h in stomach. Therefore, biphasic drug release pattern was successfully achieved through the formulation of floating bilayer tablets inthis study.

Conjugation of methotrexate (MTX) (MW 454) with different molecular weights of polyethylene glycol (PEG) including methoxy-peg (mpeg) 750 D and 5000 D and diol-peg 35000 D led to compounds that are physicochemically highly different from the parent compound, MTX. In this study, an HPLC system consisting of C8 column and UV detector (λ=342 nm), using a mixture of 30:70 v/v phosphate-citrate buffer (pH 4): methanol mobile phase, was validated for quantification of the esters. Three other HPLC methods using three mixture of buffer phosphate-citrate (pH 6): methanol at 30:70, 40:60 and 50:50 v/v, respectively, was set for estimation of partition coefficients the esters. Eight reference standard materials were selected from literature covering the retention times lower and higher than esters. An identical log P (4.3) was obtained for all three esters, despite their different molecular weights (i.e. 1200, 5500 and 35500 D theoretically). In addition the log P obtained differs from that of the parent drug (-1.4). This high difference comes probably from different ability of drug and esters in ionization of carboxylic acid groups.

Magnesium is an essential metal that has important roles in physiological function of the body organs. Ethambutol is an oral antitubercular agent with chelating effects owing to its chemical structure. The aim of present study is to determine whether ethambutol usage can alter serum magnesium concentration in patients with pulmonary tuberculosis. Sixty patients with diagnosis of pulmonary tuberculosis were enrolled in the study. Blood samples were obtained before treatment from patients. Ten days after starting anti tuberculosis therapy, second blood samples were obtained. The amounts of serum magnesium were determined in all samples by spectrophotometric method. Statistical analysis showed that serum magnesium concentrations at baseline (0.61±0.08 mmol/l) and at day 10 (0.62±0.11 mmol/l) were not different. It is possible that ethambotol does not affect magnesium concentration in tuberculosis patients, however further studies about the other cationic trace elements are recommended.

Dose-dependent pharmacokinetic of phenytoin necessitates the estimation of the maximum rate of metabolism (Vm) and the Michaelis-Menten constant (Km) in a concerned population. The aim of this study was to determine the pharmacokinetic parameters of phenytoin in a sample of Iranian patients to optimize the antiepileptic pharmacotherapy. Fourty patients who received a constant dose of phenytoin for at least three weeks were included in the study. Steady-state trough serum concentration has been used to determine the Vm and Km by Vozeh-Sheiner (orbit-graph) method. Mann-Whitney U-test and chi-square test have been used to compare the quantitative and qualitative variables respectively. Only half of the patients were in the therapeutic range. Mean Vm and mean Km were 6.12±1.01 mg/kg/day and 5.90±1.26 mg/l respectivly with significant differences [95% confidence interval of difference with the reported to mean values of 7 mg/Kg/day for Vm and 4 mg/l for Km interval -0.88 (-1.2 to 0.55) and +1.9 (1.49 to 2.31) respectively]. A trend towards higher clearance (CL) and intrinsic clearance (CLint) were observed in patients on polytherapy with phenobarbital compared to those on phenytoin monotherapy. Advanced age was inversely associated with the values of Vm and CLint in the group on monotherapy. Considering the observed lower Vm and higher Km, our population may have a lower metabolic capacity for metabolism of phenytoin, and using the estimates of Vm and Km obtained this study could help the clinicians to individualize antiepileptic therapy. In addition, the results of this study may propose that the expression of CYP2C9 and CYP2C19, as two main pathways of phenytoin metabolism, may be lower in iranians than the other populations, and phenotyping/genotyping studies of these pathways are recommended.

Remifentanil is an ultra short acting opioid that is suitable for many operations and is wildly used for induction and maintenance of anesthesia. In this article we have reported the incidence of abdominal pain after cataract surgery in patients with remifentanil based anesthesia. This study is a randomized single blind clinical trial on 300 patients who were candidates for elective cataract surgery under general anesthesia. Patients were randomly divided into two groups. In the control group (N=150) after routine monitoring, general anesthesia was induced by fentanyl, propofol and atracurium. Anesthesia was maintained by propofol infusion and 60% N2O inhalation. In remifentanil group, general anesthesia was induced by remifentanil, propofol and atracurium. Anesthesia was maintained by remifentanil infusion and 60% N2O inhalation. Abdominal pain was observed in 79 patients (52.6%) of the remifentanil group. Abdominal pain was severe in 10 cases (6.7%), which indicated a therapeutic intervention. Abdominal pain was observed in 3 cases (2%) of control group patients. Abdominal pain incidence was significantly higher in remifentanil group (p=0.0001). Postoperative nausea and vomiting (PNOV) was reported in 7 patients (4.7%) in remifentanil group and in 10 cases (6.7%) of the control group (p=0.454). Briefly, remifentanil based anesthesia caused high incidence of abdominal pain in cataract surgery patients.

Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia. The management of the blood glucose level is a critical strategy in the control of diabetes complications. Inhibitors of carbohydrate hydrolyzing enzymes have been useful as oral hypoglycemic drugs for the control of hyperglycemia especially in patients with type II disables mellitus. The goal of the present study was to investigate the inhibitory effects of six selected Allium species (A. akaka, A. ampeloprasum subsp. iranicum, A. cepa, A. hirtifolium, A. porrum and A. sativum) on α-amylase enzyme using an in vitro model. According to the results, ethanol extracts of A. akaka, A. sativum, A. porrum and A. cepa were found to have a favorable α-amylase inhibitory activity with IC50 values of 16.74, 17.95, 15.73 and 16.36 mg/ml, respectively and they did not reveal any significant differences in their IC50 values (p>0.05). However, the two other Allium species tested (A. ampeloprasum subsp. iranicum and A. hirtifolium) did not show valuable inhibitory activity.

In the present work, the bioassay screening of the essential oil and various extracts of two plants including fruits of Heracleum persicum Desf. and rhizomes of Zingiber officinale Rosc. have been studied with brine shrimp test. There is only one report about cytotoxicity of H. sphondylium in literature and so H. persicum has been used as second selection. At first essentials oil and various extracts of two plants including petroleum ether, chloroform, methanol, ether and aqueous were provided. Then, different concentrations of them were prepared. These fractions were evaluated for toxicity using Brine Shrimp Lethality assay (BSL). Each of fractions was assessed by two methods of disk and solution. Survivors were counted after 24 h. These data were processed in Probit-analysis program to estimate LC50 values (the concentration at which 50% lethality was observed) with 95% confidence intervals for statistically significant comparisons of potencies. In disc method, methanol extract of Z. officinale (LC50=28.3134 µg/ml) showed the most activity in comparison with positive standard of potassium dichromate (LC50=23.2893 µg/ml); but in solution method, essential oil of H. persicum (LC50=0.0071 µl/ml) was the most active fraction in comparison with potassium dichromate (LC50=27.7528 µg/ml). Totally, among tested fractions, essential oil of the H. persicum has been exhibited the most cytotoxicity. The essential oil of H. persicum was analyzed by GC-MS. The major constituents were hexyl butyrate and octyl acetate.

The purpose of the present study was to determine the tropane alkaloid content of four Hyoscyamus species from Iran, i.e. H. pusillus L., H. niger L., H. reticulatus L. and H. kurdicus Bornm. Determination of alkaloids was performed by the HPLC method. Samples were extracted with chloroform-methanol-25% ammonium hydroxide 15:5:1 (V/V/V). HPLC separation was performed on Eurospher C18 reversed phase column. An isocratic mixture of triethylammonium phosphate buffer (30 Mm, pH 6.2) and acetonitrile (75:25), was used as the eluent. Hyoscyamine and scopolamine were determined by the external standard method at 210 nm. All the four mentioned Hyoscyamus species contained hyoscyamine and scopolamine, but in different amounts. Scopolamine was the predominant tropane alkaloid in H. pusillus, H. niger and H. kurdicus, while, H. reticulatus contained a higher amount of hyoscyamine.

From methanolic extract of aerial parts of Peucedanum ruthenicum M. Bieb (Apiaceae) collected from Mazandaran province of Iran, four flavonoids namely Isorhamnetin 3-0-rutinoside 1, rutin 2, quercetin 3, morin 4 and two phenolic acids namely caffeic acid 5 and p-coumaric acid 6 have been isolated by Paper Chromatography (PC) and crystallization. Their structures were elucidated by MS, 1H, 13C NMR spectra