In patients with NASH, TZDs and Vitamin E improve liver histologic scores but metformin does not. Insulin resistance also improves with both TZDs and metformin. Fibrosis does not improve with any of the agents.

The transdermal drug delivery route is evolving as a potential route due to its advantages of bypassing the hepatic first pass metabolism, decreased side effects and gastrointestinal effects, improve patience compliance as it is a pain-free self-administration for patients, etc. The major setback appearing in this route is the difficulty of the drugs to penetrate through the skin as the stratum corneum (outermost layer of the skin) forms a protective barrier for the underlying tissues from the outer environment. A transdermally delivered drug can only show its action when it can cross the transdermal barrier to reach the systemic circulation and for helping on doing that the penetration enhancer are the agents which increase the permeability of the skin which on return maintains the drug level in the blood. Permeation enhancers can be of a chemical type, natural type, and physical type. The present review describes the natural permeation enhancers can be which be employed for transdermal permeation of drugs.

Objectives Analyses of seasonal variation of manic and depressive symptoms in bipolar disorder in retrospective studies examining admission data have yielded conflicting results. We examined seasonal variation of mood symptoms in a prospective cohort with long-term follow-up: The Collaborative Depression Study (CDS). Methods The CDS included participants from five academic centers with a prospective diagnosis of bipolar I or II disorder. The sample was limited to those who were followed for at least 10 years of annual or semi-annual assessments. Time series analyses and autoregressive integrated moving average (ARIMA) models were used assess seasonal patterns of manic and depressive symptoms. Results A total of 314 individuals were analyzed [bipolar I disorder: (n = 202) and bipolar II disorder: (n = 112)] with both disorders exhibiting the lowest depressive symptoms in summer and highest around the winter solstice, though the winter peak in symptoms was statistically significant only with bipolar I disorder. Variation of manic symptoms was more pronounced in bipolar II disorder, with a significant peak in hypomanic symptomatology in the months surrounding the fall equinox. Conclusions Significant seasonal variation exists in bipolar disorder with manic/hypomanic symptoms peaking around the fall equinox and depressive symptoms peaking in months surrounding the winter solstice in bipolar I disorder.

In this study, we prepared atorvastatin calcium (AVST) loaded chitosan nanoparticles to improve the oral bioavailability of the drug. Nanoparticles were prepared by solvent evaporation technique and evaluated for its particle size, entrapment efficiency, zeta potential, in vitro release and surface morphology by scanning electron microscopy (SEM). In addition, the pharmacokinetics of AVST from the optimized formulation (FT5) was compared with marketed immediate release formulation (Atorva ® ) in rabbits. Particle size of prepared nanoparticles was ranged between 179.3 ± 7.12 to 256.8 ± 8.24 nm with a low polydispersity index (PI) value. Zeta potential study showed that the particles are stable with positive values between 13.03 ± 0.32 to 46.90 ± 0.49 mV. FT-IR studies confirmed the absence of incompatibility of AVST with excipient used in the formulations. In vitro release study showed that the drug release was sustained for 48 h. Results of pharmacokinetics study showed significant changes in the pharmacokinetic parameter (2.2 fold increase in AUC) of the optimized formulation as compared to marketed formulation (Atorva ® ). Thus, the developed nanoparticles evidenced the improvement of oral bioavailability of AVST in rabbit model. Uniterms:Atorvastatin calcium/oral bioavailability/experimental study. Atorvastatin calcium/in vitro release. Atorvastatin calcium/pharmacokinetics. Nanoparticles/drugs bioavailability.No presente estudo, preparamos nanopartículas de quitosana com atorvastatina cálcica (AVST) para melhorar a biodisponibilidade oral do fármaco. As nanopartículas foram preparadas pela técnica de evaporação de solvente, avaliando-se a granulometria, a eficiência de encapsulamento, o potencial zeta, a liberação in vitro e a morfologia da superfície, por meio da microscopia eletrônica de varredura (MEV). Além disso, a farmacocinética da formulação otimizada de AVST (FT5) foi comparada com a formulação comercial, de liberação imediata, comercializada (Atorva®), em coelhos. O tamanho das das nanopartículas variou na faixa de 179,3 a 256,8 ± 7,12 ± 8,24 nm, com baixo índice polidispersibilidade (PI). O estudo do potencial Zeta mostrou que as partículas são estáveis, com valores positivos entre 13,03 ± 0,32 a 46,90 ± 0,49 mV. Os estudos de FT-IR confirmaram a ausência de incompatibilidade de AVST com o excipiente utilizado nas formulações. O estudo de liberação in vitro mostrou que liberação sustentada do fármaco por 48 horas. Os resultados do estudo farmacocinético mostraram alterações significativas nos parâmetros (aumento de 2,2 vezes na ASC) da formulação otimizada em relação à comercializada (Atorva® ). Assim, o desenvolvimento de nanopartículas evidenciou a melhora da biodisponibilidade oral de AVST em coelhos.Uniterms: Atorvastatina cálcica/biodisponibilidade oral/estudo experimental. Atorvastatina cálcica/ liberação in vitro. Atorvastatina cálcica/farmacocinética. Nanopartículas/biodisponibilidade de fármacos.

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Objective: To develop a transdermal patch of Indomethacin using patchouli oil as a natural enhancer to increase transdermal permeation of the drug from the matrix system across rat epidermis. Materials and Methods:The chemical characterization of patchouli oil was done by gas chromatography-mass spectrometry. Transdermal patches of indomethacin were formulated after studying the drug-excipient compatibility studies by differential scanning calorimetry and Fourier transform infrared spectroscopy (FTIR). The transdermal patches were evaluated for various physiochemical properties. In-vitro transdermal permeation was carried using modified Keshary-Chein diffusion cell across rat epidermis. FTIR studies of rat epidermis were done to understand the mechanism of the permeation enhancing effect of the oil from the matrix patch. Result:The results of physiochemical parameters of the transdermal patch were found satisfactory. The transdermal flux obtained of the different concentration of patchouli oil tend to increase with increasing concentration of the oil and the maximum transdermal flux of 61.92 ± 0.89 µg/cm 2 /hr was obtained with formulation F7 (containing 1% w/v of patchouli oil) which is similar to the flux of the formulation F2 containing standard enhancer dimethyl sulphoxide. The skin irritation test did not show any edema and the FTIR data of rat epidermis indicated that patchouli oil enhances transdermal permeation of indomethacin by partial extraction of lipids in the stratum corneum. Conclusion:Thus, the results showed a potential enhancing effect of patchouli oil on the transdermal permeation of the model drug indomethacin and may be used as natural permeation enhancer in transdermal drug delivery systems.

The targeted drug delivery is designed for endeavoring to concentrate the drug in the tissues of curiosity while reducing relative concentration of medication in the remaining tissues. There for drug is localized on the targeted site. Hence, surrounding tissues are not affected by the drug. Controlled drug delivery system can overcome the problems of conventional drug therapy and gives better therapeutic efficacy of a drug. Microspheres are characteristically free flowing powders consisting of proteins or synthetic polymers having a particle size ranging from 1-1000 µm. The range of Techniques for the preparation of microspheres offers a Variety of opportunities to control aspects of drug administration and enhance the therapeutic efficacy of a given drug. There are various approaches in delivering a therapeutic substance to the target site in a sustained controlled release fashion. Microspheres has a drug located centrally within the particle, where it is encased within a unique polymeric membrane. In future various other strategies, microspheres will find the central place in novel drug delivery, particularly in diseased cell sorting, diagnostics, gene and genetic materials, safe, targeted and effective in vivo delivery and supplements as miniature versions of diseased organ and tissues in the body.

In the last 30 years, particle size reduction technologies turned from an exploratory approach into a mature commercial drug delivery platform. Nanonization technologies have gained a special importance due to a steadily increasing number of development compounds showing poor aqueous solubility. Many drug delivery companies and academic research groups have contributed to the currently existing large variety of different technologies to produce drug nanoparticles. These particles consist of pure active pharmaceutical ingredient (API) and are often stabilized with surfactants and/or polymeric stabilizers adsorbed onto their surface. The mean particle size ranges normally from 1 nm up to 1000 nm.Here we review formulation aspects, characteristics and application of nanoparticle as drug delivery system