In order to examine the efficacy of paclitaxel (Taxol, Bristol-Myers Squibb) after administration locally at the tumor site, we have developed a thermo-reversible gelling formulation in poloxamer 407 (Pluronic F-127) solution. Paclitaxel was incorporated in poloxamer 407 [20% (w/w)] at 0.5- and 1.0-mg/mL concentrations. The in vitro release studies were carried out in phosphate-buffered saline (pH 7.4) at 37 degrees C. Control and paclitaxel-poloxamer 407 formulations were administered intratumorally at a dose of 20 mg/kg in B16F1 melanoma-bearing mice. The change in tumor volume as a function of time and the survival of treated animals were used as measures of efficacy. Poloxamer 407 solution undergoes a reversible sol-gel transition when the temperature is raised to above 21 degrees C. In vitro paclitaxel release from poloxamer 407 gels was very slow (only 6.1% after 6 hr) probably due to the poor aqueous solubility of the drug. Significant enhancement in the anti-tumor efficacy was noted following intratumoral administration of paclitaxel-poloxamer 407 formulation. The initial tumor growth rate was delayed by 67% and the tumor volume doubling time was increased by 72% relative to saline control. In addition, more than 91% of the tumor-bearing animals that received paclitaxel in poloxamer 407 gel survived on day 15 post-administration as compared to 58% in the control group. The results of this study show significant benefit of paclitaxel for solid tumor when administered locally in an in situ gelling poloxamer 407 formulation.

Rao et al.: Characterization and Ex Vivo studies of ItraconazoleItraconazole, an antifungal drug possess poor solubility, gastrointestinal irritation and first pass effect. Hence in the present work it was initially made as nanoparticles to facilitate absorption and at later stage nanoparticles loaded transdermal patches were developed using promising nanoparticles. Nanoparticles were prepared with Eudragit RL 100 by solvent displacement technique. Formulations F1 to F9 were prepared by using different concentrations of Eudragit RL 100 and polyvinyl alcohol and evaluated for drug content, drug release, entrapment efficiency and mean particle size. The selected formulation was lyophilized to incorporate these formed nanoparticles into transdermal patch by varying concentrations of hydroxy propyl methyl cellulose K100M, polyvinyl alcohol and polyethylene glycol 400. The obtained patches were evaluated for thickness, tensile strength, folding endurance, moisture absorption and moisture content and the drug release showed biphasic release. All the formulations followed first order kinetics, diffusion controlled and fickian release. Flux (ex vivo) studies on rat skin of optimized formulation have high flux of 63.24 µg/cm 2 /h compared with pure drug, prepared itraconazole ointment 39.15 µg/ cm 2 /h and prepared itraconazole gel 40.01 µg/cm 2 /h. The permeability of itraconazole nanoparticle loaded transdermal patch showed 2.63 folds enhancement compared to pure drug. Scanning electron microscopes clearly showed the drug loaded nanoparticle embedment in polymeric transdermal patch. Formulated nanoparticle loaded itraconazole transdermal patch can be successfully used as a carrier for enhancing transdermal permeation and the bioavailability.

Objective: Ramelteon, is a sleep agent that selectively binds to the MT1 and MT2 receptors in the suprachiasmatic nucleus (SCN), instead of binding to GABAA receptors. In the present research work, the formulation of ramelteon targeted to colon by using various polymers developed. Methods: Colon-targeted tablets were prepared in two steps. Initially, core tablets were prepared and then the tablets were coated by using different pH dependent polymers. Ethylcellulose, Eudragit RLPO and L100 were used as enteric coating polymers. The precompression blend of all formulations was subjected to various flow property tests and all the formulations were passed the tests. The tablets were coated by using polymers and the coated tablets were subjected to physical characterization, drug content, in vitro drug release and kinetics of drug release. Results: Among all the formulations, F4 formulation was found to be optimized as it was retarded the drug release up to 18 h and showed maximum of 99.25% drug release. It followed the first-order kinetics mechanism. All the formulations having Korsmeyer-Peppas ‘n’ values are in the range of 0.540 to 0.818. Hence, it was concluded that the prepared formulations followed non-Fickian diffusion. Conclusion: An effective and stable remelteon colon targeted formulation developed for treating insomnia.