IRANIAN JOURNAL OF PHARMACEUTICAL SCIENCES
Year:2011 | Volume:7 | Issue:4|Papers Count:8

Several plant extracts and phytoconstituents, despite having excellent bioactivity in vitro, demonstrate less or no in vivo actions due to their poor lipid solubility or improper molecular size or destruction in gut. Drug delivery system for polyphenolic phytoconstituents (phytosomes) was prepared by complexing polyphenolic phytoconstituents with phospholipid mainly phosphatidylcholine which bind components to each other on a molecular level. Bioavailability is enhanced due to their capacity to cross the lipid rich bio-membranes and to protect the valuable components of the herbal extract from destruction by digestive secretions and gut bacteria. Phytosomes have the capacity to deliver the standardized plant extracts and phytoconstituents through several routes of drug administration. Only a few natural drugs have been formulated and are available in the market as phytosomes. With wide range of applications of phytosomes numerous studies are undergoing and lots more is expected in the forthcoming years. The techniques used for such formulations are patentable and highly profitable.

In this study, the effect of recrystallization of naproxen in the presence of hydroxypropyl cellulose (HPC) on the release rate of drug was investigated. Crystals were generated by the anti-solvent approach using the HPC solution in water as the anti-solvent. The samples were subjected to various physicochemical evaluations such as crystal size, scanning electron microscopy, Fourier transform infrared (FTIR) spectroscopy, solubility, wettability and dissolution studies. Results revealed that HPC play a key role in controlling the primary crystal size, morphology, size and surface properties of naproxen agglomerates. Crystallization of naproxen in the presence of HPC caused a marked modification of its dissolution. The particles obtained in the presence of HPC exhibited slower dissolution rate compared to those produced in the absence of HPC. This was attributed to the adsorption of HPC on the surface of the naproxen crystals. It was shown that the solubility of naproxen increased in solution containing HPC. Moreover, there was a significant difference between the solubility of untreated naproxen and that of samples crystallized in the presence of HPC in water. Contact angle measurements revealed that control crystals obtained in the absence of HPC have a greater contact angle than those produced in the presence of HPC. FT-IR spectroscopy results indicated the absence of any interaction between drug and HPC. This study highlights the influence of polymeric additive on the crystallization process leading to modified performance.

An oral suspension could a suitable dosage form for the geriatric patients. The calcium alginate coated ion exchange resinate of propranolol hydrochloride were prepared using Amber lite IR-120 by solvent evaporation. Microcapsules of propranolol hydrochloride resinate were prepared by solvent evaporation technique, the suspensions were prepared by using deionised water as the vehicle. Methyl cellulose and Tween 80 were used as suspending agents in four different concentrations: 0.5, 1, 1.5 and 2%. The suspensions were evaluated for physical stability, redispersibilty and in vitro release patterns. Microcapsules of propranolol hydrochloride corresponding to drug polymer ratios of 1:1.0, 1:1.5, 1:2.0, 1:2.5 and 1:3.0 were evaluated for physical stability, percentage yield, particle size, and in vitro drug release profile. The drug loading capacity of ion exchange resine was found to be 41% (w/v). The suspensions were prepared with 1.5% Tween 80 had good physical stability and redispersibilty and in vitro release patterns, and were also suitable for sustained release formulation. Therefore, calcium alginate coated propranolol hydrochloride formulation as oral sustained suspension is an effective system, which can be suitable dosage form for geriatric use.

Sirolimus is a potent immunosuppressive agent administered as prophylactic agent to prevent rejection after organ transplantation. Sirolimus must be used within a narrow therapeutic window. Due to inter- and intra-variability, sirolimus blood concentrations may be affected, therefore, there is no possibility of predicting the sirolimus blood concentrations based on the dose patients received. Therapeutic drug monitoring (TDM) of whole blood is an important part of immunosuppressive therapy and is mandatory for sirolimus dosage individualization. The objective of this study was to present a validated method for the analysis of sirolimus in human blood by LC/MS spectrometry and also evaluation of correlation between blood sirolimus concentration and laboratory parameters. We examined a group of 32 patients receiving sirolimus at different stages after organ (kidney, liver or pancreas) transplantation. The mean sirolimus concentration was 10.2 ng/ml (range: 1.3-30.1 ng/ml). The assay was validated for a linear dynamic range of 1-50 ng/ml. The correlation coefficient (r) was 0.995. The within-run imprecision CV (%) for concentrations (1 and 10 ng/ml) were 14.7 and 2.2%, respectively. The between run imprecision CV (%) for the same concentrations were 14.8 and 3.4%, respectively.Limit of quantification (LOQ) and limit of detection (LOD) were defined as 1 and 0.3 ng/ml, respectively. Analytic recovery was 98±2% over a range of 1-50 ng/ml.Statistical results showed no correlation between sirolimus blood concentration and the dosage in patients receiving sirolimus. Also, no relationship between drug concentration in blood and laboratory parameters was seen.

Ricin, the toxic lectin extracted from the castor bean plant (Ricinus communis), consists of an A chain (RTA) and a B chain (RTB). Anti-A chain Abs and anti-B chain Abs can neutralize toxins in vivo and in vitro via blocking the binding of the toxin to the cell. Also, RTB protein is able to serve as an antigen deliver to the mucosal immune system and act as an immunoadjuant. Here, the genomic DNA was extracted from the fresh leave of the castor plant. TheRTB gene was amplified by PCR. The prokaryotic expression vector pET-28a (+) - RTB was constructed, and used to transform E. coli Rosetta (DE3). The expression of recombinant protein induced by IPTG was examined by SDS-PAGE. Western blot were used to determine immunoreactivity of RTB-His by a rabbit monoclonal antibodies against His-tag. The SDS-PAGE profile exhibited the constructed prokaryotic expression efficiently produced RTB at the 1 mmol/L of IPTG. Addition of glycine and Triton X-100 enhanced native extracellular protein excreted into the culture medium. Anti-RTB polyclonal serum was generated by repeated immunization of mice with recombinant RTB protein. Finally, the antigenicity of recombinant RTB was identified by Western blot and indirect ELISA. A relative high titer of anti-RTB antibody was detected after the fourth injection. Western blot analysis was carried out with the polyclonal antibody revealed almost a 32-kDa band which corresponds to RTB protein. In conclusion, we herein report the expression of fully biologically active RTB as a plant lectin by a new strategy. This recombinant Ricin protein could be a promising drug for cancer therapy, vaccine as an immune response enhancement and even viral infected cells.

The study was designed with an aim to evaluate the protective effects of reduced glutathione on cyclophosphamide induced lipid peroxidation and also changes in cholesterol content. Goat liver and white New Zealand rabbit were used as lipid source for the models. Lipid peroxidation study was performed by measuring the malondialdehyde, 4-hydroxy-2-nonenal, reduced glutathione and nitric oxide content of tissue homogenates or rabbit blood. In the cholesterol profile total cholesterol and high density lipoprotein cholesterol content of rabbit blood was determined. The data presented in this work demonstrate the lipid peroxidation induction potential of cyclophosphamide and the antiperoxidative potential of reduced glutathione on cyclophosphamide-induced lipid peroxidation. It was also observed that reduced glutathione has protective effect on cyclophosphamide-induced changes in cholesterol content. A significant correlation was also found between malondialdehyde, 4-hydroxy-2-nonenal with total cholesterol as well as between reduced glutathione and nitric oxide with HDL cholesterol. These findings from both in vitro as well as in vivo models indicate the lipid peroxidation induction potential of cyclophosphamide which may be related to its toxic potential. The results also suggest the antiperoxidative effects of reduced glutathione and demonstrate its potential to reduce cyclophosphamide-induced lipid peroxidation and thus to increase therapeutic index of the drug by way of reducing toxicity that may be mediated through free radical mechanisms.

Ricinus communisLinn. (Euphorbiaceae) is a soft wooded tree widely prevalent throughout tropics regions of the world which have a warm temperature. In the Indian system of medicine, the leaves, roots and seed oil of this plant have been used for the treatment of inflammation and liver disorders for a long time. In the present study, the protective effects of ethanol extract of Ricinus communis L. leaves on carbon tetrachloride-induced liver damage were investigated in rats. Results were compared with those of silymarin, a standard hepatoprotective drug. It was found that an increase in the activities of serum transaminases and the level of liver lipid peroxidation, protein, glycogen and the activities of acid and alkaline phosphatase in liver induced by CCl4 were significantly inhibited by treatment with Ricinus communis ethanolic extract (250.500 mg/kg b.wt). In addition, the depletion of glutathione level and adenosine triphosphatase activity observed in the CCl4-induced rat liver were effectively prevented by treatment with Ricinus communis ethanolic extract (250.500mg/kg b.wt). Histopathological examination further confirmed the hepatoprotective activity of Ricinus communis ethanol extract when compared with the CCl4-induced control rats. In conclusion, these results indicate that the ethanol extract of Ricinus communis ethanolic extract exhibits hepatoprotective action.

Fruits, leaves and tuberous roots of Momordicia diocia are used in India as a folk remedy for treatment of a wide range of disorders. The objective of this study was to evaluate the hepatprotective activity of the fruits of Momordicia diocia by preparing different extracts and the resultant extract were screened for the hepatprotective activity. The ethyl acetate and ethanolic extracts of Momordicia diocia fruits were prepared and subjected for phytochemical screening and tested for their hepatprotective activity in CCl4-induced hepatotoxicity in rats. Phytochemical screening showed positive test for steroids, triterpenoids and glycosides (Etoh extract). The ethyl acetate and ethanolic extracts showed a significant hepatprotective activity at a dose of 200 mg/kg (p.o.). The results suggested that Momordica diociafruits possess potential hepatprotective activity against CCl4 hepatotoxicity possibly by antioxidant activity.