Genetic Diversity and Anti-Oxidative Potential of Streptomyces spp. Isolated from Unexplored Niches of Meghalaya, India.

Streptomyces is genetically and functionally diverse genus known to produce a wide array of phenolics and flavonoids with significant biotechnological applications. 52 isolates belonging to 26 species of Streptomyces collected from Meghalaya, India were analyzed for their genetic diversity using BOX-PCR. Significant inter- and intra- generic diversity was observed among the Streptomyces isolates especially those belonging to S. cacaoi, S. lavendulae, S. olivochromogenes, S. aureus, S. flavovirens. During bioactivity screening of the isolates, S. rectiviolaceus MJM72 recorded the highest DPPH activity (77.13 ± 0.91%) whereas S. antimycoticus MSCA162 showed excellent ABTS radical scavenging activity (99.65 ± 0.41%). On the other hand, S. novaecaesareae MJM58 had the highest (756.4 ± 7.38 µg GAE g-1 fresh weight) phenolic content while S. rectiviolaceus MJM72 was recorded with the highest flavonoid content (69.3 ± 0.12 µg QE g-1 fresh weight). As compared to total flavonoid content, total phenolic content had a stronger correlation with antioxidant activities. HPLC analysis of five selected isolates showed presence of gallic acid and pyrocatechol as predominant phenolics. In case of flavonoids, three isolates showed presence of rutin with S. rochei MSCA130 having the highest rutin content (0.95 µg g-1 fresh weight). The results of this study showed high genetic diversity and antioxidant potential among the Streptomyces isolates.

Ramifications of Vorticity on Aggregation and Activation of Platelets in Bi-Leaflet Mechanical Heart Valve: Fluid-Structure-Interaction Study.

Bileaflet mechanical heart valves (BMHV) are widely implanted to replace diseased heart valves. Despite many improvements in design, these valves still suffer from various complications, such as valve dysfunction, tissue overgrowth, hemolysis, and thromboembolism. Thrombosis and thromboembolism are believed to be initiated by platelet activation due to contact with foreign surfaces and nonphysiological flow patterns. The implantation of the valve causes nonphysiological patterns of vortex shedding behind the leaflets. This study signifies the importance of vorticity in platelet activation and aggregation in BMHV implants. A two-phase model with the first Eulerian phase for blood and the second discrete phase for platelets is used here. The generalized cross model of viscosity has been used to simulate the non-Newtonian viscosity of blood. A fluid-structure-interaction model has been used to simulate the motion of leaflets. This study has also estimated the platelet activation state (PAS), which is the mathematical estimation of the degree of activation of platelets due to flow-induced shear stresses that cause thrombus formation. The regions in the fluid domain with a higher vorticity field have been found to contain platelets with relatively higher PAS than regions with relatively lower vorticity fields. Also, this study has quantitatively reported the effect of vorticity on platelet aggregation. Platelet densities in fluid areas with higher vorticity are higher than densities in fluid areas with lower vorticity, indicating that highly activated platelets aggregate in areas with stronger vorticity.

Assessment and visualization of hemodynamic loading in aneurysm sac and neck: Effect of foam insertion.

Shape memory polymer (SMP) foam is often proposed as the future alternative of coils in aneurysm treatment devices. Present work numerically investigates the unsteady, three-dimensional simulation of blood flow in a cerebral aneurysm filled with SMP foam. Simulations are conducted on patient-specific geometries with realistic blood velocity waveform imposed at the inlet while SMP foam is treated as a porous medium. The present study introduces a "loading risk map" that helps to visualize the hemodynamic effect of foam insertion on the aneurysm sac and neck. The loading risk maps suggest that while the SMP foam subdues the flow and wall shear pulsations in the aneurysm sac, the pressure distribution is minimally affected. The maps suggest that while the downstream lip is the most risk-prone site for both geometries, downstream vascular anatomy significantly influences foam efficiency in reducing pressure and wall shear stress loading.

Nose to brain delivery of antiretroviral drugs in the treatment of neuroAIDS.

NeuroAIDS (Neuro Acquired Immunodeficiency Syndrome) or HIV (Human Immunodeficiency Virus) associated neuronal abnormality is continuing to be a significant health issue among AIDS patients even under the treatment of combined antiretroviral therapy (cART). Injury and damage to neurons of the brain are the prime causes of neuroAIDS, which happens due to the ingress of HIV by direct permeation across the blood-brain barrier (BBB) or else via peripherally infected macrophage into the central nervous system (CNS). The BBB performs as a stringent barricade for the delivery of therapeutics drugs. The intranasal route of drug administration exhibits as a non-invasive technique to bypass the BBB for the delivery of antiretroviral drugs and other active pharmaceutical ingredients inside the brain and CNS. This method is fruitful for the drugs that are unable to invade the BBB to show its action in the CNS and thus erase the demand of systemic delivery and thereby shrink systemic side effects. Drug delivery from the nose to the brain/CNS takes very less time through both olfactory and trigeminal nerves. Intranasal delivery does not require the involvement of any receptor as it occurs by an extracellular route. Nose to brain delivery also involves nasal associated lymphatic tissues (NALT) and deep cervical lymph nodes. However, very little research has been done to explore the utility of nose to brain delivery of antiretroviral drugs in the treatment of neuroAIDS. This review focuses on the potential of nasal route for the effective delivery of antiretroviral nanoformulations directly from nose to the brain.

Rutin-phospholipid complex in polymer matrix for long-term delivery of rutin via skin for the treatment of inflammatory diseases.

The drug with poor oral bioavailability necessitates the development of novel carrier for efficient drug delivery. This paper reports the rutin-phospholipid complex in polymer matrix for sustained delivery of rutin via the skin for the treatment of acute and chronic inflammatory diseases. Rutin in phospholipid complex (RNPs) are better soluble and permeable than the free rutin. The RNPs-loaded polymeric matrix patch with moderate adhesiveness was developed for convenient means of long term drug application on the skin. The patch was analysed for physicochemical properties, ex vivo skin permeability and in vivo efficacy in rat paw oedema model. The skin targeting efficacy was analysed by CLSM study. Optimized formulation (F2) showed 31 ± 2.32% and 26.56 ± 5.52% skin permeation at 24 h across excised rat skin and human cadaver skin, respectively. The sustained anti-inflammatory effect of the patch formulation in rat paw oedema model confirmed its unique in vivo efficacy over the conventional diclofenac gel. The CLSM study confirmed the localization of RNPs in the dermis for sustained anti-inflammatory effect. Our results suggest that the developed patch has a potential for long term site specific delivery of rutin in arthritic patients.

Sustained Anti-inflammatory Effect of Resveratrol-Phospholipid Complex Embedded Polymeric Patch.

Resveratrol-phospholipid complex (Phytosome®) (RSVP) was found better aqueous soluble and permeable than free resveratrol (RSV). RSVPs were incorporated in polymeric patch prepared by solvent casting method using Eudragit RL 100, PVP K30, and PEG 400 for application on dermal sites for sustained treating of inflammation. Prepared patches were evaluated for various physicochemical properties, surface morphology by SEM, TEM, and compatibility of patch components by FT-IR and DSC studies. Optimized formulation (F9) gave 95.79 ± 3.02% drug release and 51.36% (4.28 ± 0.48 mg/cm2) skin permeation after 24 h. Skin extract when examined for drug accumulation showed 38.31 ± 2.42% drug content. FE-SEM images of the patch taken after drug release and skin permeation studies showed that RSVPs in polymeric patch are stable and retain their structure after 24 h long exposure to physiologic environment. Sustained anti-inflammatory effect was established in carrageenan-induced paw edema model in which test formulation gave 84.10% inhibition of inflammation at 24 h as compared to 39.58% for standard diclofenac sodium gel. The CLSM study confirmed the localization of RSVPs for a longer period, thus enabling drug targeting to the dermis for sustained effect. Skin irritation test on rabbit revealed that the patches are safe for skin application. Histological observations suggested that after exposure to the permeants, the SC integrity had not altered and no evidence of presence of inflammatory cells found. RSVP (Phytosome®) containing patches abled to give sustained therapeutic effect that may be useful in treating acute and chronic inflammation.

Nano-ART and NeuroAIDS.

Human immunodeficiency virus (HIV) is a neurotropic virus that enters the central nervous system (CNS) early in the course of infection. Although highly active antiretroviral therapy (HAART) has resulted in remarkable decline in the morbidity and mortality in AIDS patients, controlling HIV infections still remains a global health priority. HIV access to the CNS serves as the natural viral preserve because most antiretroviral (ARV) drugs possess inadequate or zero delivery across the brain barriers. The structure of the blood-brain barrier (BBB), the presence of efflux pumps, and the expression of metabolic enzymes pose hurdles for ARV drug-brain entry. Thus, development of target-specific, effective, safe, and controllable drug delivery approach is an important health priority for global elimination of AIDS progression. Nanoformulations can circumvent the BBB to improve CNS-directed drug delivery by affecting such pumps and enzymes. Alternatively, they can be optimized to affect their size, shape, and protein and lipid coatings to facilitate drug uptake, release, and ingress across the barrier. Improved drug delivery to the CNS would affect pharmacokinetic and drug biodistribution properties. This review focuses on how nanotechnology can serve to improve the delivery of antiretroviral medicines, termed NanoART, across the BBB and affect the biodistribution and clinical benefit for NeuroAIDS.

Curcumin-docetaxel co-loaded nanosuspension for enhanced anti-breast cancer activity.

PURPOSE: A curcumin-docetaxel co-loaded nanosuspension with increased anti-breast cancer activity was developed. Curcumin is a potential anticancer agent with p-glycoprotein (p-gp) inhibiting activity may be co-administered with docetaxel as a nanosuspension to enhance its anticancer effect by increasing the oral bioavailability and decreasing drug efflux. METHODS: Nanosuspensions of curcumin and docetaxel were prepared by precipitation-homozenisation technique and evaluated for particle size, polydispersity, zeta potential and drug release. The in vitro MTT assay was conducted using MCF-7 for anti-breast cancer activity. The in vivo biodistribution by radiolabeling and tumor inhibition study was conducted in mice. RESULTS: Homogenous nanosuspensions of 80 ± 20 nm were obtained with increased solubility. The drugs as nanosuspensions showed higher cytotoxicity on MCF-7 cell line compared to their suspensions due to the increased in vitro cellular uptake. Due to this increased solubility, sensitization of tumor cells and inhibition of p-gp the in-vivo results showed greater tumor inhibition rate of up to 70% in MCF-7 treated mice. Histopathological results showed higher apoptotic activity and reduced level of angiogenesis. CONCLUSIONS: The in vitro and in vivo study of the nanosuspensions has shown that Co-administration of Curcumin as a p-gp inhibitor with docetaxel may have the potential to increase the anti-breast cancer efficacy of both drugs.

Genomics and natural products: role of bioinformatics and recent patents.

The post genomic era has promised major breakthroughs in personalized medicine which will improve a patient's health by selecting treatments including diet based on the patient's unique DNA sequence. The post genomic era is allowing scientists and clinicians to examine an individuals' DNA and then recommend the best diet in order to remain healthy and attenuate disease processes which the individual might be predisposed to because of their genetic make-up, e.g., cardiovascular disease. Nutrigenomics and nutrigenetics are related terms to pharmacogenomics and pharmacogenetics with an emphasis on diet or nutrition. There has been an increasing interest in consumers on natural medicines or Nutraceuticals in order to remain healthy. The post genomic era will allow a patient to visit their physician who will screen the patients DNA on a silicon chip. This will indicate which of the patient's genes have polymorphisms, e.g., a single nucleotide polymorphism (SNP) that might lead the patient to be more susceptible to certain diseases and then the physician could prescribe the appropriate dietary supplements to prevent or diminish these potential diseases. Several recently published patents are discussed in the article covering recent developments in the field.

Nanoprecipitation with sonication for enhancement of oral bioavailability of furosemide.

Furosemide is a weakly acidic diuretic indicated for treatment of edema and hypertension. It has very poor solubility but high permeability through stomach and upper gastrointestinal tract (GIT). Due to its limited solubility it has poor and variable oral bioavailibility of 10-90%. The aim of this study was to enhance the oral bioavailibilty of furosemide by preparation of nanosuspensions. The nanosuspensions were prepared by nanoprecipitation with sonication using DMSO (dimethyl sulfoxide) as a solvent and water as an antisolvent (NA). The prepared nanosuspensions were sterically stabilized with polyvinyl acetate (PVA). These were characterized for particle size, zeta potential, polydispersity index, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) pattern and release behavior. The average particle size of furosemide nanoparticles were found to be in the range of 150-300 nm. This was further confirmed by SEM photograph. The particle size varies with an increase in concentration of drug and stabilizer. The preparations showed negative zeta potential and polydispersity index in the range of 0.3 +/- 0.1. DSC and XRD studies indicated that the crystalline furosemide drug was converted to amorphous form upon precipitation into nanoparticles. The saturation solubility of prepared furosemide nanoparticles markedly increased compared to the original drug in simulated gastric fluid. The release profiles of nanosuspension formulation showed up to 81.2% release in 4 h. It may be concluded that the nanoprecipitation with ultrasonication have potential to formulate homogenous nanosuspensions with uniform sized amorphous nanoparticles of furosemide. Polyvinyl acetate can be used as a suitable steric stabilizer to prepare stable furosemide nanosuspensions. The enhanced saturation solubility in simulated gastric fluid may lead to enhanced absorption of furosemide.

Preparation and in vitro/in vivo evaluation of felodipine nanosuspension.

The purpose of this study was to develop a nanosuspension of a poorly soluble drug felodipine by nanoprecipitation to achieve superior in vitro dissolution and high oral absorption in vivo in rats. Felodipine nanosuspensions were prepared by precipitation with ultrasonication method using polyvinyl alcohol (PVA) and hydroxy propyl methyl cellulose (HPMC) as stabilizers. The particle size of nanosuspension with PVA was 60-200 nm, while with HPMC is 300-410 nm. The in vitro dissolution and pharmacokinetics of optimized nanosuspensions were studied after oral administration in male wistar rats. The results showed significant improvement during in vitro dissolution and in vivo plasma level. Dissolution studies of lyophillised nanoparticles showed that up to 93.0 % dissolved in 2 h. In the in vivo evaluation, nanosuspension exhibited significant increase in AUC0-24, C max and decrease in t max. The findings revealed that particle size reduction can influence felodipine absorption in gastrointestinal tract and nanosuspension can enhance oral bioavailability of felodipine in rats.

Ex vivo permeation kinetics of zidovudine from pseudolatex acrylic film across pig ear epidermis.

The permeation of ionic compounds through lipophilic skin membrane can be enhanced by converting the impermeable ionized drug into a more permeable unionized form with pH-adjusting excipients. The osmotic influx of water into the device core, upon application on the human skin, dissolve the drug and pH-adjusting adjuvant allowing the partitioning and subsequent permeation of unionized drug from the transdermal device core. The present investigation was aimed to evaluate the feasibility of water activated pH-controlled pseudolatex films for transdermal delivery of zidovudine by ex vivo tests. The monolithic pseudolatex transdermal film of zidovudine was prepared by solvent change followed by solvent casting technique using Eudragit RL 100 and Eudragit RS 100 in varying proportions with pH 7.4 in the device core. The prepared films were of desired physicochemical properties. The SEM photomicrographs of drug loaded formulations exhibited uniformity with rough surface and no traces of crack or pores. The ex vivo skin permeation study across pig ear epidermis in Keshary-Chien glass diffusion cell showed that the drug permeability was controlled by the osmotic influx of water into the device core and consequent partition of dissolve drug into and diffusion through the skin. The formulation F2a with 10 % w/w of zidovudine dispersed in the polymer matrix composed of Eudragit RL 100 and Eudragit RS 100 at the ratio of 1:2, respectively, showed nearly the desired flux at 239.09 µg/cm(2)/h. A patch area of 117.48 cm(2) would be required for transdermal delivery of zidovudine to obtain therapeutic plasma concentration at 0.3 µg/ml.

Sorbitan ester niosomes for topical delivery of rofecoxib.

The aim of the present investigation is to encapsulate rofecoxib in niosomes and incorporate the prepared niosomes into dermal gel base for sustained therapeutic action. Niosomes were prepared by lipid film hydration technique and were analyzed for size, entrapment efficiency and drug retention capacity. Niosomal vesicles were then incorporated into blank carbopol gel to form niosomal gel. The in vitro permeation study across pig skin was performed using Keshary-Chien glass diffusion cell. The size and entrapment efficiency of the niosomal vesicles increased with gradual increase in HLB value of nonionic surfactants used. Maximum drug entrapment was observed with Span 20 with HLB value of 8.6 and drug leakage from vesicles was less at refrigerated condition than at the room temperature. Higher proportion of cholesterol made the niosomal formulation more stable with high drug retention properties. The niosomal gel showed a prolong drug release behavior compared to plain drug gel. Differential scanning calorimetric study of drug loaded gel and pig skin after permeation study confirmed inertness of carbopol gel base toward rofecoxib and absence of drug metabolism in the skin during permeation study, respectively. The niosomal formulations were successfully prepared by lipid film hydration technique using cholesterol and Span as nonionic surfactant. Presence of cholesterol made niosomes more stable with high drug entrapment efficiency and retention properties. The lower flux value of niosomal gel as compared to plain drug gel across pig skin assured the prolong drug release behavior with sustained action.

Ex vivo and in vivo evaluation of transdermal formulation of trazodone hydrochloride.

The aim of the present investigation is to evaluate the biopharmaceutical behaviors of the matrix patch containing trazodone hydrochloride (TZN) following transdermal administration in rabbits. The ex vivo skin permeation study was performed using Keshary-Chien glass diffusion cell and mouse epidermis with intact stratum corneum as membrane. The phosphate buffer of pH 7.4 was used as receptor solution at 37 degrees C. TZN patch was applied to the inner pinna skin of the rabbit. TZN transdermal absorption from patch was compared to that from peroral TZN solution in rabbit. A steady-state skin permeation rate of 134.09 +/- 2.49 microg/cm2/h was achieved from the matrix patch across mouse epidermis after an initial lag time of approximately 3.5 h. The steady-state transdermal TZN concentration of 2.3 microg/mL was achieved in rabbit from the matrix patch after an initial lag time of approximately 2 h. The Cmax of peroral TZN solution was calculated to be 5.84 microg/mL at a Tmax of 2 h indicating its rapid absorption compared to the transdermal administration with a Tmax of 5 h. The ex vivo and in vivo biopharmaceutical parameters were in good agreement with respect to steady-state plasma TZN concentration and lag time. The plasma level of TZN following transdermal application could be maintained for 24 h. The transdermal dose achieved a much higher steady-state blood concentration in rabbit compared with the effective blood concentration in human. The observed steady-state blood concentration may appear to be within the expected therapeutic range in human with a higher clearance value compared to that in rabbit.

Evaluation of diltiazem hydrochloride-loaded mucoadhesive microspheres prepared by emulsification-internal gelation technique.

The problems of frequent administration and variable low bioavailability (40-60%) after oral administration of conventional dosage forms of diltiazem can be attenuated by designing it in the form of mucoadhesive microspheres which would prolong the residence time at the absorption site to facilitate intimate contact with the absorption surface and thereby improve and enhance the bioavailability. Diltiazem-loaded mucoadhesive microspheres were successfully prepared by emulsification-internal gelation technique with a maximum incorporation efficiency of 93.29 +/- 0.26%. The scanning electron microscopic study indicated that the microspheres were spherical in shape and the drug remained dispersed in the polymer matrix at amorphous state, which was further confirmed by x-ray diffraction analysis. The in vitro wash-off test indicated that the microspheres had good mucoadhesive properties. The wash-off was faster at simulated intestinal fluid (phosphate buffer, pH 7.4) than that at simulated gastric fluid (0.1 M HCl, pH 1.2). The in vitro drug release mechanism was non-fickian type controlled by swelling and relaxation of polymer. There was no significant change in drug content and cumulative drug release of drug-loaded microspheres stored at different storage condition after 8 weeks of study.

Recovery of 99mTc from Na2[99Mo]MoO4 solution obtained from reactor-produced (n,gamma) 99Mo using a tiny Dowex-1 column in tandem with a small alumina column.

A simple separation technique of (99m)Tc from Na(2)[(99)Mo]MoO(4) in sodium hydroxide solution obtained from the (98)Mo(n,gamma)(99)Mo reaction is described. Low to medium specific activity (99)Mo-molybdate solution of 7.4-18.5GBq (200-500mCi) in sodium hydroxide was passed through a tiny Dowex-1 column (25mg) to separate the (99m)Tc from the (99)Mo; subsequently the (99m)Tc was eluted from the Dowex 1 column with tetrabutylammonium bromide (TBAB) solution (1mg/5ml methylene chloride). The TBAB solution was passed through a small alumina column (1.5g) where the (99m)Tc is retained and separated from TBAB and CH(2)Cl(2). Technetium-99m from the alumina column was finally eluted with 5ml saline leaving any traces of (99)Mo on the alumina column. The separation yield was about 90% (n=10). The method has applicability for decontamination of (99g)Tc from spent (99)Mo waste solution and recovery of (99g)Tc for research use. The procedure should also be equally applicable for recovery of (188)ReO(4) from (188)WO(4) in a radioisotope laboratory.

Preparation and evaluation of a new radiopharmaceutical for radiosynovectomy, 111Ag-labelled hydroxyapatite (HA) particles.

Many radionuclides, namely, 166Ho, 90Y, 165Dy, 32P, 198Au, 186Re, etc. have been used for radio-synovectomy. Silver-111 (T 1/2 7.45 d) can be produced in a nuclear reactor and is a potential therapeutic radionuclide decaying by beta(-) emission (92% E beta max=1.037MeV and 8% by beta(-) decay associated with emission of gamma-rays (E gamma=245.4keV, I gamma=1.33%; E gamma=342.1keV, I gamma=6.7%)). Because of the production feasibility and favourable nuclear properties, 111Ag may find use as a suitable radionuclide for radio-synovectomy. Hydroxyapatite (HA), Ca10(PO4)6(OH)2 is one of the preferred particulates for this application. In this work, [111Ag]Ag-HA particulates were successfully prepared with high-labelling yield ( approximately 97%) at various pH values. The radiochemical purity of the [111Ag]Ag-HA particles was 99.9%. Stability studies for 7 days showed that the [111Ag]Ag-HA particles retained their stability. gamma camera images at 15 min, 24h and 5 d after injection of the particles into rabbits revealed the retention of the activity in the synovial joints of the knee, thereby indicating excellent in vivo stability of [111Ag]Ag-HA particles. Therefore, [111Ag]Ag-HA particles would be a potential therapeutic agent in the management of arthritis.

Evaluation of furosemide-loaded alginate microspheres prepared by ionotropic external gelation technique.

Alginate microspheres containing furosemide were prepared by the ionotropic external gelation technique using Ca2+, Al3+ and Ba2+ ions. The incorporation efficiency of the prepared microspheres ranged between 65% and 93%. The effect of sodium alginate concentration, cross-linking ions and drying conditions was evaluated with respect to entrapment efficiency, particle size, surface characteristics and in vitro release behavior. Infrared spectroscopic study confirmed the drug-polymer compatibility. Differential scanning calorimetric analysis revealed that the drug was molecularly dispersed in the alginate microsphere matrices. Scanning electron microscopic study of microspheres showed the rough surface due to higher concentration of drug molecules dispersed at molecular level in the alginate matrices. The mean particle size and entrapment efficiency were found to be varied by changing various formulation parameters. The in vitro release profile could be altered significantly by changing various formulation parameters to give a sustained release of drug from the microspheres. The kinetic modeling of the release data indicate that furosemide release from the alginate microspheres follow anomalous transport mechanism after an initial lag period when the drug release mechanism was found to be Fickian diffusion controlled.

Formulation and ex vivo evaluation of rofecoxib gel for topical application.

The potential gastrointestinal disorders associated with oral administration of rofecoxib can be avoided by delivering the drug to the inflammation site at a sustained, concentrated level over an extended period of time. Hydroxypropylmethylcellulose (HPMC), sodium alginate and Carbopol 940 were used in an attempt to develop topical gel formulations of rofecoxib. The effects of polymer composition on the rate of drug release from the gel formulations were examined through cellulose membrane mounting on a Keshary-Chien diffusion cell. The effects of initial drug concentration and viscosity on the permeation rate of rofecoxib from the gel formulations were evaluated using rat epidermis at 37 +/- 0.5 degrees C. The anti-inflammatory activity of the rofecoxib gel formulation was evaluated using the rat hind paw edema model. The gel formulation consisting of 4% w/w sodium alginate-Carbopol 940 at 3:1 ratio was found to be suitable for topical application based on in vitro evaluation and ex vivo permeation studies. The drug permeation rate increased with an increase of the initial drug concentration in gels up to 25% w/w. An inverse relationship was observed between the in vitro drug release rate/ex vivo permeation rate and viscosity of the gel formulations. The anti-inflammatory activity of 4% w/w sodium alginate-Carbopol 940 gel containing 25% w/w rofecoxib in the rat hind paw edema model reveals that the drug was delivered to the inflammation site at a controlled level over a period of 6 h. These results suggest the feasibility of the topical gel formulation of rofecoxib.

Effect of different terpene-containing essential oils on percutaneous absorption of trazodone hydrochloride through mouse epidermis.

The aim of our study was to investigate the enhancing effect of several essential oils in the percutaneous absorption of trazodone hydrochloride (TZN). For this purpose, fennel oil, eucalyptus oil, citronella oil, and mentha oil were applied on the skin membrane in three different ways: included in the transdermal device, as a pretreatment, or both. To investigate the effect of penetration enhancers used in this study on the percutaneous absorption of TZN through mouse epidermis, Keshary-Chien diffusion cells were employed. The receptor phase was constantly stirring saline phosphate buffer of pH 7.4 at 37 +/- 1 degrees C. Results showed that pretreatment of skin with essential oils increases the flux values of TZN compared with the values obtained when the same essential oils were included in the transdermal devices. The percutaneous penetration flux for TZN was increased with skin pretreatment by 10% essential oils in the following order: fennel oil > eucalyptus oil > citronella oil > mentha oil. The amount of TZN retained in the skin after pretreatment with essential oils was found to be very similar in all cases and much higher than in the experiments without skin pretreatment.