The aim of the present study was to investigate transfersomes as a transdermal delivery system for the poorly soluble drug, sertraline, in order to overcome the troubles associated with its oral delivery. Different transfersomal formulations were prepared with non-ionic surfactant (span 80), soya lecithin, and carbopol 940 by the rotary evaporation sonication method. The prepared formulations were characterized for light microscopy, particle size analysis, drug entrapment, turbidity, drug content, rheological studies, in vitro release, ex vivo permeation, and stability studies. The optimized formulation was evaluated for in vivo studies using the modified forced swim model test. FTIR studies showed compatibility of the drug with excipients. The result revealed that sertraline in all of the formulations was successfully entrapped with uniform drug content. Transfersomal gel containing 1.6% of the drug and 20% of span 80 was concluded to be the optimized formulation (EL-SP4), as it showed maximum drug entrapment (90.4±0.15%) and cumulative percent drug release(73.8%). The ex vivo permeation profile of EL-SP4 was compared with the transfersomal suspension, control gel, and drug solution. The transfersomal gel showed a significantly higher (p<0.05) cumulative amount of drug permeation and flux along with lower lag time than the drug solution and drug gel. It also owed to better applicability due to the higher viscosity imparted by the gel rather than the transfersomal suspension, and no skin irritation was observed. The modified forced swim test in mice revealed that the transfersomal gel had better antidepressant activity as compared to the control gel. Thus, the study substantiated that the transfersomal gel can be used as a feasible alternative to the conventional formulations of sertraline with advanced permeation characteristics for transdermal application.

The aim of the present study was to investigate the nanoemulgel as transdermal delivery system for poorly water soluble drug, ketoprofen, in order to overcome the troubles associated with its oral delivery. Different nanoemulsion components (oil, surfactant, and cosurfactant) were selected on the basis of solubility and emulsification ability. Pseudoternary phase diagrams were constructed using titration method to figure out the concentration range of components. Carbomer 940 was added as gel matrix to convert nanoemulsion into nanoemulgel. Drug loaded nanoemulsions and nanoemulgels were characterized for particle size, TEM, viscosity, conductivity, spreadability, rheological behavior, and permeation studies using Wistar rat skin and stability studies. Transdermal permeation of ketoprofen from nanoemulgels was determined by using Franz diffusion cell. Nanoemulgel containing 6% oleic acid as oil, 35% Tween 80, and Transcutol P as surfactant cosurfactant mixture, 56.5% water, 2.5% drug, and 0.6% carbomer was concluded as optimized formulation (NG6). Theex vivopermeation profile of optimized formulation was compared with nanoemulsion and marketed formulation (Fastum). Nanoemulgel showed significantly higher (P<0.05) cumulative amount of drug permeated and flux along with lower lag time and skin retention than marketed formulation. Thus, the study substantiated that nanoemulgel formulation can be used as a feasible alternative to conventional formulations of ketoprofen with advanced permeation characteristics for transdermal application.

Lovastatin (LOV) belongs to the class of cholesterol lowering drugs and is the first clinically used statin. It is a prodrug which lowers the cholesterol level through reversible competitive inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, an enzyme involved in biosynthesis of cholesterol. It is available as conventional and extended release tablets, but its low aqueous solubility (4´10 -4 mg mL -1 ) finally escorts it to low oral bioavailability (less than 5 %). In addition, it undergoes extensive first pass metabolism; as a consequence of hepatic extraction it leads to low and variable availability of the drug to the general circulation. Therefore improvement in aqueous solubility of LOV is the foremost aim (1, 2). Self-microemulsifying drug delivery system (SMEDDS) of lovastatin was aimed at overcoming the problems of poor solubility and bioavailability. The formulation strategy included selection of oil phase based on saturated solubility studies and surfactant and co-surfactant screening on the basis of their emulsification ability. Ternary phase diagrams were constructed to identify the self-emulsifying region. Capryol 90 (20 %) as oil, Cremophore RH40 (40 %) as surfactant and Transcutol P (40 %) as co-surfactant were concluded to be optimized components. The prepared SMEDDS was characterized through its droplet size, zeta potential, emulsification time, rheological determination and transmission electron microscopy. The optimized formulation exhibited 94 % in vitro drug release, which was significantly higher than that of the drug solution. In vivo studies using the Triton-induced hyperlipidemia model in Wistar rats revealed considerable reduction in lipid levels compared to pure lovastatin. The study confirmed the potential of lovastatin SMEDDS for oral administration.

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Facilitation of experimental convulsions by reserpine (1) which persisted for several days was found to correspond with depletion of brain amines including 5-hydroxytryp tamine, adrenaline and noradrenaline. Decrease in the concentration of these amines was found to be responsible for such experimental convulsions. It has also been reported that inhibitors of the enzyme monoamine oxidase, responsible for the metabolism of bio genic amines, have pronounced anticonvulsant effect (2) presumably due to an increase in the concentration of brain amines. In the present study some quinazolone hydrazides (3) and quinazolone hydrazines (4) synthesized in this laboratory as monoamine oxidase inhibitors were tested for their ability to protect against convulsions produced in rats by subcutaneous injections of pentylenetetrazol. Attempts were made to investigate if the enzyme inhibition is related to anticonvulsant effects elicited by such 2,3-disubstituted quinazolones which have been shown to possess pronounced hypnotic (5) and anticon vulsant properties (6). METHODSThe synthesis of newer 2,3-disubstituted quinazolones and their in vitro effect on the monoamine oxidase activity of isolated rat liver mitochondria using tyramine as substrate have been reported elsewhere (3,4). In the present study in vivo inhibition of monoamine oxidase by quinazolone hydrazides and quinazolone hydrazines was determined by DOPA (3,4-dihydroxyphenylalanine) response test (7) and reserpine reversal test (8). DOPA response testAlbino mice of either sex weighing between 15-20 g were used. The mice were divided in groups of five and kept in separate cages. A group of 5 mice was used for each dose of these agents. Aqueous solution of DL-DOPA was prepared by first dissolving the powder in 1 N HCl and then adjusting the pH with dilute sodium hydroxide to as close to neutral as possible (6.0) avoiding any precipitate. All injections were made within 1 hour after the preparation of the solution (7). Quinazolone hydrazides and