Current Issue : 5 Volume : 2011 Issue Number : 1-2 Articles : 5 Articles
The purpose of the present study was to prepare a novel domperidone hydrogel. The domperidone dispersion was prepared by the solvent evaporation method. The characteristics of domperidone dispersion were measured by dynamic light scattering (DLS), scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffractometry, and solubility test, respectively. Domperidone hydrogel was prepared by directly incorporating the domperidone dispersion in Carbopol hydrogel to increase its mucoadhesive properties to gastrointestinal tract (GIT). The in vivo pharmacokinetic and pharmacodynamic studies were investigated to evaluate the relative oral bioavailability and the propulsion efficacy of domperidone hydrogel as compared with market domperidone tablet (Motilium tablet). The particle size of domperidone dispersion in distilled water was 454.0?nm. The results of DSC and X-ray indicated that domperidone in dispersion was in amorphous state. The solubility of domperidone in the dispersion in distilled water, pH of 1, 5, and 7 buffer solution was 45.7-, 63.9-, 13.1-, and 3.7-fold higher than that of raw domperidone, respectively. The area under the plasma concentration curve (AUC0ââ?¬â??24) in domperidone hydrogel was 2.2-fold higher than that of tablet. The prolonged propulsion efficacy in the domperidone hydrogel group compared to that in tablet group was observed in the pharmacodynamic test....
Background: Flurbiprofen is a non-selective cyclo-oxygenase inhibitor, member of series of alkanoic acid derivatives, has anti-inflammatory, analgesic activity. Also used to treat gout, osteoarthritis, rheumatoid arthritis and is effective in inhibiting surgically induced miosis in human eyes while cataract extraction. Oral sustained release formulation as a novel matrix system of flurbiprofen tablets were prepared using Carboxy methylcellulose as release retardant.\r\nObjective: The aim of present study was comparative bioavailability assessment of newly developed flurbiprofen matrix tablets for sustained delivery, with commercially available Froben SR.\r\nMethods: Randomized, open-label, 2-periods, cross-over study conducted on 24 male healthy volunteers in Pakistan. Small batch of flurbiprofen matrix tablets were manufactured and evaluated according to Pharmacopoeial specifications. Each volunteer received a 200-mg tablet of the test and reference formulations, separated by a 7-day washout period. Blood samples were obtained before dosing 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours after drug administration. Safety monitoring was performed which includes adverse events. Plasma concentrations of the 2 formulations were determined, and pharmacokinetic parameters were compared using noncompartmental analysis. In-vivo disposition kinetics was evaluated using single dose, cross over, complete two period of treatment design in twenty four healthy male human volunteers; the drug was assayed in plasma using HPLC-UV detection, and results were compared. Various pharmacokinetic parameters (Cmax, Tmax, area under the curve [AUC0-24], mean residence time) and relative bioavailability were compared.\r\nResults: No significant differences were found for Cmax, Tmax,AUC and other parameters. The rate and extent of drug release from matrix tablets was not significantly different from commercially available Froben SR tablets. An in vivo result indicates prolonged blood levels with delayed peak and comparable bioavailability.\r\nConclusions: The matrix tablets could also provide, sustained, gastrointestinal environmentalindependent release that may result in an improved therapeutic efficacy....
Background\nDue to their nanometric scale (50 nm) along with their biomimetic properties, lipid nanocapsules loaded with Rhenium-188 (LNC188Re-SSS) constitute a promising radiopharmaceutical carrier for hepatocellular carcinoma treatment as its size may improve tumor penetration in comparison with microspheres devices. This study was conducted to confirm the feasibility and to assess the efficacy of internal radiation with LNC188Re-SSS in a chemically induced hepatocellular carcinoma rat model.\nMethodology/Principal Findings\nAnimals were treated with an injection of LNC188Re-SSS (80 MBq or 120 MBq). The treated animals (80 MBq, n = 12; 120 MBq, n = 11) were compared with sham (n = 12), blank LNC (n = 7) and 188Re-perrhenate (n = 4) animals. The evaluation criteria included rat survival, tumor volume assessment, and vascular endothelial growth factor quantification. Following treatment with LNC188Re-SSS (80 MBq) therapeutic efficiency was demonstrated by an increase in the median survival from 54 to 107% compared with control groups with up to 7 long-term survivors in the LNC188Re-SSS group. Decreased vascular endothelial growth factor expression in the treated rats could indicate alterations in the angiogenesis process.\nConclusions/Significance\nOverall, these results demonstrate that internal radiation with LNC188Re-SSS is a promising new strategy for hepatocellular carcinoma treatment....
Cytotoxic chemotherapy of cancer is limited by serious, sometimes life-threatening, side effects that arise from toxicities to sensitive normal cells because the therapies are not selective for malignant cells. So how can they be selectively improved? Alternative pharmaceutical formulations of anti-cancer agents have been investigated in order to improve conventional chemotherapy treatment. These formulations are associated with problems like severe toxic side effects on healthy organs, drug resistance and limited access of the drug to the tumor sites suggested the need to focus on site-specific controlled drug delivery systems. In response to these concerns, we have developed a new drug delivery system based on magnetic erythrocytes engineered with a viral spike fusion protein. This new erythrocyte-based drug delivery system has the potential for magnetic-controlled site-specific localization and highly efficient fusion capability with the targeted cells. Here we show that the erythro-magneto-HA virosomes drug delivery system is able to attach and fuse with the...
Background\r\nTargeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System) neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy and limit clinical utility for many classes of pharmaceuticals. Axonal transport from the periphery offers a possible selective route, but there has been little progress towards design of agents that can accomplish targeted delivery via this intraneural route. To achieve this goal, we developed a tripartite molecular construction concept involving an axonal transport facilitator molecule, a polymer linker, and a large number of drug molecules conjugated to the linker, then sought to evaluate its neurobiology and pharmacological behavior.\r\nResults\r\nWe developed chemical synthesis methodologies for assembling these tripartite complexes using a variety of axonal transport facilitators including nerve growth factor, wheat germ agglutinin, and synthetic facilitators derived from phage display work. Loading of up to 100 drug molecules per complex was achieved. Conjugation methods were used that allowed the drugs to be released in active form inside the cell body after transport. Intramuscular and intradermal injection proved effective for introducing pharmacologically effective doses into selected populations of CNS neurons. Pharmacological efficacy with gabapentin in a paw withdrawal latency model revealed a ten fold increase in half life and a 300 fold decrease in necessary dose relative to systemic administration for gabapentin when the drug was delivered by axonal transport using the tripartite vehicle.\r\nConclusion\r\nSpecific targeting of selected subpopulations of CNS neurons for drug delivery by axonal transport holds great promise. The data shown here provide a basic framework for the intraneural pharmacology of this tripartite complex. The pharmacologically efficacious drug delivery demonstrated here verify the fundamental feasibility of using axonal transport for targeted drug delivery....
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