Iranian Journal of Pharmaceutical Sciences

The aim of this study is to prepare novel sorbitol based extended release tablets by melt dispersion method using carbamazepine as a model drug. Carbamazepine was melted along with sugar alcohol to get melt dispersion granules (MGDs) and was characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (XRD) and solubility study. The physical and chemical parameters of MDGs and tablets were measured while drug release was studied using USP II dissolution apparatus. The release data were subjected to different models to evaluate their release kinetics and mechanisms. Evaluation of MDGs using XRD and DSC indicated that melt dispersion process converted crystalline carbamazepine and sugar alcohol into lower crystallinity with no significant improvement in solubility. The drug release rate was found to be affected by sugar alcohol concentration, particle size of MDGs, the nature of co-excipients, agitation rate and hardness. The kinetics of carbamazepine release from formulation (F3) showed best fit to Higuchi and super case II transport mechanism. It can be concluded that sorbitol is a suitable matrix-forming agent to sustain the release of low soluble drug carbamazepine. Melt dispersion technique using sorbitol is proved to be a promising technique for controlled drug delivery.

Uricase or Urate oxidase (urate:oxygen oxidoreductase, EC 1.7.3.3), a peroxisomal enzyme which is found in many bacteria, catalyzes the oxidative opening of the purine ring of urate to yield allantoin, carbon dioxide, and hydrogen peroxide. In this study, the phylogeny of urate oxidase (uricase) producing bacteria was studied based on gene sequences of 16S rRNA and uricase protein. Representative and type strains (52 strains total) of most of the known species were analyzed. The acquired sequences (rDNA sequences of the 16S rRNA genes and the amino acid sequences of uricase) were aligned with the Clustal W program using MEGA software version 4.0. Phylogenetic trees were constructed with the neighbor-joining method, and were bootstrapped with 500 replications of each sequence. The large congruence of
phylogenetic relationship between the uricase gene and of 16S rRNA gives considerable support to the phylogeny of urate oxidase producing bacteria which was previously suggested on the basis of 16S rRNA sequences. The observed consistency promotes the idea that each of these genes shared a common evolutionary history in uricase producing bacteria we have analyzed.

It has been proposed that organic nitrates such as glyceryl trinitrate (GTN), used in the treatment of cardiovascular diseases, act by producing nitric oxide (NO). However, the biochemical pathway for NO formation from GTN is not well understood. In the present study, we showed that nitrate formation from GTN, by isolated rat hepatocytes, was inhibited about 50% when cellular glutathione was
depleted and about 40% when cytochrome P-450 was inactivated by SKF525A. This suggests that GTN is metabolized and/or NO is formed by three pathways in rat hepatocytes: 1) denitrification of GTN by GSH/GSH transferase system; 2) reduction of GTN by reduced cytochrome P-450; and 3) GTN can directly react with protein thiol groups of cellular macromolecules (transnitrosation). At much higher
concentrations, GTN was toxic towards hepatocytes (LC50= 2 mM for 2 h of incubation) and cytotoxicity was accompanied by GSH and ATP depletion. Depleting GSH and/or inactivating cytochrome P-450 beforehand markedly increased GTN cytotoxicity. The permeable thiol reductant dithioteritol unlike antioxidants was found to be an effective antidote, even if added to the cells an hour after GTN. The results
suggest that GTN-induced cytotoxicity is mediated by transnitrosyllation of mitochondrial, structural and vital protein thiols.

Cancers belong to a group of disorders which are very important for researchers. Because they have several types and cause mortality in human beings. Many investigations are performing in order to introduce cheaper drugs with lower side effects especially with natural sources. Ferula genus grows all over the world but some of them are endemic to Iran. Many investigations have proved different biological activity of these plants. It has been established that some Ferula species have cytotoxic activity. In the present study, cytotoxic effects of F. persica var. persica and F. hezarlalezarica which are endemic to Iran have been evaluated against tumor cell lines MCF7, HepG2, HT29, A549, and a normal cell line MDBK using MTT method. Total extracts of the plants aerial parts were prepared by 80% methanol and maceration method. Different fractions of the plants were obtained using hexane, chloroform, ethyl acetate, pure or 50% methanol. Total extracts and different fractions were used for MTT assay. The results showed that among the
examined samples, only hexane and chloroform fractions of the plants had cytotoxic effects up to concentration of 100 μg/ml. So that, extracts of F. persica var. persica were more cytotoxic than F. hezarlalezarica (IC50s, 22.3-71.8 μg/ml for F. persica var. persica and 76.7-105.3 μg/ml for F. hezarlalehzarica). It seems that both plants are suitable for further investigations in cancer researches.

Electrochemical aptamer-based sensors attract a lot of interest as useful methods because of their low cost, accuracy, sensitivity, and simplicity. An electro-active redox molecule comprises the main part of the electrochemical-based sensors. Ferrocene is one of the most popular redox molecule used in biosensor fabrication. But, instability of ferrocenium ion in strong nucleophilic reagents and chloride containing
solutions is one of the main problems of this redox molecule. In this study, Juglone is used as an effective quinone redox molecule for aptasensor designing in different pH ranges and different concentrations of chloride ion. The voltammetric studies showed that the electrochemical response of sensor increased by raising the buffer ionic concentration and the sensor accuracy in 7.0 to 8.0 pH range as well. According
to the findings, Juglone could be used as an effective redox molecule in high concentrations of chloride containing solutions in the 7.0 pH.

Resonance light scattering (RLS) intensity of silver nanoparticles in the presence of sodium dodecylsulphate was quenched on addition of sulfasalzine. The quenching extent was shown to be proportional to the sulfasalazine concentration. Effect of different parameters such as pH, volume and kind of buffer, silver nanoparticles concentration, sodium dodecylsulphate (SDS) concentration, and waiting time on
RLS quenching were investigated. Calibration curve was linear in the range of 10 to 70 μg ml-1. Detection limit was determined as 0.012 mg.ml-1. The method was successfully applied to the determination of sulfasalazine in different batch numbers of sulfasalazine tablets. The results were compared with those determined by USP method. Reasonable agreements were observed.

Bone is the third most common site of metastatic disease. Bone pain is the major source of morbidity associated bone metastasis. Bone-seeking radiopharmaceuticals have been applied for many years. The ability to simultaneously treat multiple sites of disease with a more probable therapeutic effect in earlier phases of metastatic disease is one of the advantages of radiopharmaceuticals. 175Yb is one
of the radioisotopes with suitable properties for developing various nuclear medicine agents. Some of these proper properties include 4.2 days half-life, gamma-rays emitted, radionuclidic purity. Radiopharmaceuticals capable of targeting bone tumors generally use phosphonic acid functionality as the targeting moiety. In this direction cyclic tetraphosphonate, 1,4,7,10-tetraazacyclododecane-1,4,7,10-
tetraaminomethylenephosphonate (DOTMP) has been labeled with 175YbCl3. Production, quality control and biodistribution studies of 175Yb-DOTMP were targeted in this study. 175Yb chloride with mean specific activity of 31 mCi/mg was obtained by thermal neutron flux (3×1013 n.cm-2.s-1) of a natural Yb2O3 sample (isotopic purity of 31.8% for 174Yb) in the Tehran Research Reactor (TRR). Radiolabeling was completed in one h by the addition of DOTMP at room temperature. The radiochemical purity was determined using ITLC and it was more than 98%. The results of biodistribution animal studies are excellent. It was rapidly taken up in the bone in 2 h after injection (ID/g%=3.92) and reminded after 4 d (ID/g%=3.91).

Todays, the parent company has a great role in managing and monitoring subsidiaries and companies in promoting their industrial activities. But, the main problem for pharmaceutical parent companies is the lack of clarity and confusion of responsibilities between units. Successful parenting needs to create the element of 'fit' between the ways parent operates – parent characteristics – and its business
characteristics. However, the main parent characteristic is the parent structure, and restructuring is the main challenge in unstable pharmaceutical market. In fact, the parent strategy should determine how value can be added to every organizational structure and parent structure should be proportionate to its dominant value creation strategy. The value drivers are very different in pharmaceutical industry regarding the fast changing technology. The aim of this study is to explore an appropriate valuecreating structure for the largest pharmaceutical parent company in Iran, Tamin Pharmaceutical Investment Company (TPICO). This study concentrates on the sources of value in this special domain and restructuring the parent company by considering the dominant value-creating strategy and pharmaceutical value drivers.