DARU, Journal of Pharmaceutical Sciences
Volume:19 Issue: 3, 2011

Achillea L. (Compositae or Asteraceae) is a widely distributed medicinal plant throughout the world and has been used since ancient time. Popular indications of the several species of this genus include treatment of wounds, bleedings, headache, infammation, pains, spasmodic diseases, fatulence and dyspepsia. Phytochemical investigations of Achillea species have revealed that many components from this genus are highly bioactive. There are many reports on the mentioned folk and traditional effects. Although, the medicinal properties of Achillea plants are recognized worldwide, there are only one review article mainly about the structures of the phytochemical constituents of Achillea. The present paper reviews the medicinal properties of various species of Achillea, which have been examined on the basis of the scientifc in vitro, in vivo or clinical evaluations. Various effects of these plants may be due to the presence of a broad range of secondary active metabolites such as favonoids, phenolic acids, coumarins, terpenoids (monoterpenes, sesquiterpenes, diterpenes, triterpenes) and sterols which have been frequently reported from Achillea species.

Background and purpose of the study: Technetium-99m is the major radionuclide used in the world and mainly is provided by fission product. However extensive research has been conducted on the use of accelerators for production of 99mTc. This investigation reports the production of 99mTc radioisotope using cyclotrons followed by the preparation, quality control and biodistribution studies of four major Tc-radiopharmaceuticals. The high purity molybdenum natural target (130mg/cm2) was irradiated in a Cyclone 30 accelerator using 160 µA of 25 MeV proton beam energy for 1000 µA-h. After dissolution, the technetium radionuclides were extracted using methyl ethyl ketone (MEK) followed by preparation of Tc-MIBI, Tc-DTPA, Tc-DMSA and Tc-phytate as radiopharmaceutical samples. The results of quality controls and animal biodistribution studies showed successful production of Tc radionuclides (including 99mTc) in the bombarded target and subsequent labelling of the kit with Tc. The developed high power Mo target if constructed using enriched 100Mo, could be a practical method for large-scale production of 99mTc and promising as an alternative to fission product 99Mo-99mTc generators for local applications near cyclotron facilities.

Background and the purpose of the study: The purpose of the present investigation was to characterize, optimize and evaluate microballoons of Propranolol hydrochloride and to increase its boioavailability by increasing the retention time of the drug in the gastrointestinal tract. Propranolol hydrochloride-loaded microballoons were prepared by the non-aqueous O/O emulsion solvent diffusion evaporation method using Eudragit RSPO as polymer. It was found that preparation temperature determined the formation of cavity inside the microballoon and this in turn determined the buoyancy. Microballoons were subjected to particle size determination, micromeritic properties, buoyancy, entrapment efficiency, drug loading, in vitro drug release and IR study. The correlation between the buoyancy, bulk density and porosity of microballoons were elucidated. The release rate was determined in simulated gastric fluid (SGF) of pH 1.2 at 37±0.5 °C. The microballoons presented spherical and smooth morphologies (SEM) and were porous due to presence of hollow cavity. Microballoons remained buoyant for >12 hrs for the optimized formulation. The formulation demonstrated favorable in vitro floating and release characteristics. The encapsulation efficiency was high. In vitro dissolution kinetics followed the Higuchi model. The drug release from microballoons was mainly controlled by diffusion and showed a biphasic pattern with an initial burst release, followed by sustained release for 12 hrs. The amount of the drug which released up to 12 hrs was 82.05±0.64%. Statistical analysis (ANOVA) showed significant difference (p < 0.05) in the cumulative amount of drug released after 30 min, and up to 12 hrs from optimized formulations. The designed system for propanolol would possibly be advantageous in terms of increased bioavailability and patient compliance.

Background and the purpose of the study: Baclofen, a centrally acting skeletal muscle relaxant, is indicated in the long-term treatment of spasticity. It is difficult to formulate baclofen sustained release dosage forms because its absorption on arrival to colon (or even before) is low or nonexistent. In the present investigation efforts were made to improve the bioavailability of baclofen by increasing the residence time of the drug through sustained-release matrix tablet formulation via gastroretentive mechanism. Tablets were prepared by wet granulation technique. The influence of gas generating and gel forming agents, amount of baclofen and total weight of tablet on physical properties, in vitro buoyancy, floating lag time, drug release, DSC, X-ray studies were investigated. The release mechanisms were explored and explained by applying zero order, first order, Higuchi and Korsmeyer equations. The selected formulations were subjected to stability study for the period of three months. For all formulations, kinetics of drug release from tablet followed Higuchi's square root of time kinetic treatment heralding diffusion as predominant mechanism of drug release. Formulations containing 20 mg and 40 mg (F-1 and F-7) showed similar release profiles. There was no significant change in the selected formulations, when subjected to accelerated stability conditions over a period of three months. X-ray imaging in six healthy human volunteers revealed a mean gastric retention period of 5.50±0.7 hrs for the selected formulation.Stable, sustained release effervescent floating matrix tablets of baclofen could be prepared by wet granulation technique.

Background and the purpose of the study: As a novel drug in the treatment of cardiac diseases, dl-praeruptorin A (Pd-Ia) is the major active component of traditional herbal medicine Peucedanum praeruptorum Dunn and is metabolized primarily via cytochrome P450 isozymes (CYP) 3A1 and 3A2 in rats. In the present study, the influence of liver cirrhosis on pharmacokinetics of Pd-Ia and hepatic mRNA expression of CYP3A1 and 3A2 in rats with experimental liver cirrhosis (LC rats) were evaluated. Pd-Ia was given intravenously (5 mg·kg-1) to LC rats induced by dimethylnitrosamine and pharmacokinetic variables were measured. Enzyme kinetic metabolism of Pd-Ia in rat hepatic microsomes was also investigated and hepatic mRNA expression of CYP3A1 and 3A2 were measured by real-time PCR.Results and major After intravenous administration in LC rats, the area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) was significantly greater than that in control rats, which might be due to slower rate of the hepatic blood flow and significant slower hepatic intrinsic clearance (CLint) in rats. The decreased metabolic clearance of Pd-Ia in LC rats might be at least partly caused by the decreased levels of CYP3A1 and 3A2 responsible for Pd-Ia metabolism. These findings may provide new insights into the inter- and intra-individual pharmacokinetic variability of Pd-Ia.

Background and the purpose of the study:Many factors have been reported that contribute to the wide intra- and inter-patient variability of Busulfan (Bu) disposition. The purpose of this study was to develop a population pharmacokinetic model and to determine the covariates affecting the pharmacokinetics (PK) of Bu in Iranian adult patients who received oral high-dose as a conditioning regimen before Hematopoietic Stem Cell Transplantation (HSCT). A population PK analysis was performed in 30 patients who received an oral Bu and cyclophosphamide regimen before HSCT. Bu was given orally according to the protocol of the institution. In order to prevent seizures caused by Bu, phenytoin was administered orally one hour before each dose of Bu.A total of 180 blood samples were analyzed by HPLC and PK parameters were estimated by the non-linear mixed effect model by MONOLIX 3.1 program. A one-compartment model with an additive error model was used to describe the concentration-time profile of Bu.CL=13.4[1+ (0.141×Disease)],Vd=42.6[1+0.010× (Weight - 63.9)]Patient's disease and weight was found to be the determinant factors for clearance (CL) and the volume of distribution (Vd) according to Monolix analysis. The covariate entered in final model followed by these equations:In this limited study, the age (15-43 years) had no significant effect. For a patient weighting 60 kg, the typical CL and Vd were estimated to be 13.4 l/hr and 42.6 L, respectively. The interindividual variability of CL and Vd were 13.6 and 6.3%, respectively. There was no significant metabolic induction in these four days as is evident by comparing the trough levels of Bu. However it should be mentioned that, one tailed t-test p-values of the days of two and three, two and four and three and four were 0.083, 0.069 and 0.388, respectively.Major Results of this study showed that the type of disease was a determinant of CL and the weight of patient was a determinant of Vd for Bu population PK parameters. A reliable PK parameters and Css, estimated from only one plasma concentrations (5 hrs after the first dose), were validated. Since these methods require few sampling and are easy to be used, the limited sampling methods might be advantageous in the routine clinical practice.

Back ground and the purpose of study: Sumatriptan succinate is a Serotonin 5- HT1 receptor agonist, used in treatment of migraine. It is absorbed rapidly but incompletely when given orally and undergoes first - pass metabolism, resulting in a low absolute bioavailability of about 15%. The aim of this work was to design mucoadhesive bilayered buccal tablets of sumatriptan succinate to improve its bioavailability. Mucoadhesive polymers carbopol 934 (Carbopol), HPMC K4M, HPMC K15M along with ethyl cellulose as an impermeable backing layer were used for the preparation of mucoadhesive bilayered tablets. In vivo bioavailability studies was also conducted in rabbits for optimized formulation using oral solution of sumatriptan succinate as standard.Bilayered buccal tablets (BBT) containing the mixture of Carbopol and HPMC K4M in the ratio 1:1 (T1) had the maximum percentage of in vitro drug release within 6 hrs. The optimized formulation (T1) followed non-Fickian release mechanism. The percentage relative bioavailability of sumatriptan succinate from selected bilayered buccal tablets (T1) was found to be 140.78%. Bilayered buccal tablets of sumatriptan succinate was successfully prepared with improved bioavailability.

Some studies have demonstrated that Reaction Time (RT) is longer in patients with ADHD which in turn may be associated with educational and occupational impairment and increased driving risks. Any alteration on RT which is induced by the treatment in this population may have great consequences positively or negatively. This study was designed to examine the effects of reboxetine on RT in adults with Attention Deficit-Hyperactivity Disorder (ADHD).A total of 30 adult patients with ADHD who did not suffer from any other major psychiatric disorder were eligible to participate in this double blind, placebo controlled study. Patients were randomly assigned to receive either reboxetine (4 mg/day for one week, then 8 mg/day) or placebo for 4 weeks. RT was assessed at baseline and after 4 weeks by validated software which collects and analyses the data for auditory and visual stimulants. Numbers of correct responses, omission and substitution errors for each stimulus were calculated.Regarding visual tasks and in comparison with baseline scores, the number of correct responses increased significantly and the number of omission errors decreased significantly after 4 weeks of treatment (P<0.05) in both groups. However, with regard to auditory tasks scores, no significant differences were found at the end of the study compared to the baseline in each of the two groups. Additionally, no significant differences were noted between the two groups when both visual and auditory tasks were considered.Results of this study showed that reboxetine did not affect the RT of the patients when both visual and auditory tasks were assessed. Further studies with larger number of patients and for a longer period of time are required to confirm the result of this study.

Background and the purpose of the study:Indoleamine 2,3-dioxygenase (IDO) suppresses adaptive immune response. The purpose of this study was to determine the effect of the IDO inhibitor namely 1-methyl-DL-tryptophan (DL-1-MT) on antibody production after vaccination with hepatitis B surface (HBs) antigen.Four groups of BALB/c mice were immunized with a HBs antigen vaccine. In the first group the vaccine had no DL-1-MT, whereas in the other three groups the vaccine contained 1 mg, 10 mg and 20 mg DL-1-MT. Blood samples were collected 5 weeks post-vaccination and anti-HBs antibodies in the serum were measured by ELISA.Compared to the three groups of mice that were immunized with the vaccines containing DL-1-MT, serum anti-HBs level was much higher in the mice that were immunized with the vaccine with out DL-1-MT.Inhibition of IDO at the time of vaccination decreased humoral immune response to HBs antigen vaccine. The idea that IDO activity is simply immunosuppressive may need to be re-evaluated.

Purpose of the study:to determine the efficacy, adverse effects and safety of a new Iranian generic product of deferasirox (Osveral®) in Iranian transfusion dependent major thalassemic (TD-MT) patients.In 9 main thalassemia treatment centers, all of TD-MT patients (aged ≥2 yrs) with serum ferritin (SF) levels≥1000 ng/ml, or >100 ml/kg of RBC transfusion, who could not tolerate parental iron chelating were recruited regardless of their previous iron chelation therapy. Periodical clinical and laboratory evaluations were conducted for adverse effects (AEs). Primary efficacy end point was Mean of Relative Change of Serum Ferritin (MRC-SF) from the baseline level during one year. Analysis of variance (ANOVA), t test, chi-square or Fisher exact test were used for statistic analysis appropriately (P values <0.05 were considered as statistical significant).In 407 cases the male/female ratio was 0.98. Mean age was 11.5±7.4 (2-58) years. The mean of initiating dose of Osveral® and mean usage dose during the study was 23.5±4.9 mg/kg and 24.9 ± 4.9 mg/kg respectively. MRC-SF was -11.44% ±38.92 and it showed significant decline in SF (P value<0.001) one hundred and forty eight patients out of 407 patients experienced at least one. AE, the most common of them were transient increase in serum creatinin (97;24.1%) and > 5 time increase in transaminases (24;5.89%).The causes of discontinuation of treatment were non-satisfactory treatment (24; 5.8%), poor or non-compliance of patients (21;5.1%), and adverse effects (13; 3.1%). A detailed comparison with similar studies on deferasirox (Exjade®) shows a promising efficacy and safety for its Iranian generic product (Osveral ®).