6 billion doses. So far US$600 million has been spent in efforts to develop TB vaccine candidates. Efforts to develop a live attenuated (LA) tetravalent dengue vaccine in partnership with the National Institutes of Allergy and Infectious Diseases – NIH and the Butantan Institute were reported by A. Precioso. Dengue incidence has increased 30-fold over the last 50 years with up to 100 million infections annually in over 100 endemic countries, in tropical and sub-tropical areas. The LA vaccine approach stimulates both cellular and humoral immunity, inducing

a strong memory response and durable immune response. LA vaccines for other related flaviviruses such as yellow fever and Japanese encephalitis virus have been

successfully developed and LA vaccines click here can be very economical to produce, helping to secure vaccine access. Ideally, the vaccine must confer protective immunity against all selleck chemical four dengue virus serotypes. Regarding safety, the attenuated virus must not be transmissible via mosquitoes and must show genetic and potency stability. Six monovalent candidates, developed and tested in pre-clinical and initial clinical studies in the USA, demonstrated that each of monovalent vaccine candidates was attenuated and immunogenic in mice and Rhesus macaques. The monovalent candidate vaccines, evaluated in over 750 volunteers in US, were found to be safe and immunogenic when administered as a single subcutaneous dose of

103 PFU/mL. Subjects did not develop a dengue-like illness and local reactogenicity was minimal. Studies in flavivirus-naïve adults (US) demonstrated that the tetravalent mixtures are safe and viremia remained very low. Immunogenicity measured after 90 days demonstrated multivalent seroconversion rate of 74%. Phase II, stepwise, randomized, double-blind and controlled clinical trial to evaluate the safety and immunogenicity of the lyophilized formulation of the vaccine made at Butantan started in Brazil in October 2013. L. Yang provided an overview of a successful partnership between CNBG and PATH2 for the development and global supply of a live attenuated Japanese encephalitis old (JE) vaccine at the Chengdu Institute for Biological Products (CDIBP) in China. CDIBP has one of the largest development and manufacture capabilities of biological products within CNBG with an annual production capacity for more than 100 million doses and over 950 staff. The JE project’s strategy at CDIBP, focused on improving the GMP level and achieving WHO prequalification. Critical success factors included the use of software tools, the organization of the project team, the teamwork spirit and defining the framework or rules for the project monitoring, measurement and improvement. Key milestones were defined in 2004 with an assessment by PATH, site inspection by WHO in May 2013 and prequalification in October 2013.

The disintegration test revealed that the all the liquisolid tablet were disintegrated within 15 min as shown in Table 5, which is as per specifications given for the uncoated tablets in the IP.12 Surface response graph of disintegration time [Fig. 2(B)] showing that as, as drug: excipient ratio

(R) and as drug conc. in liquid medication increases disintegration time is increased. Regression values of X1 and X2 for disintegration time were as shown in Table 4. Microcrystalline cellulose and sodium starch glycolate accelerates the disintegration of liquisolid compacts and improve dissolution of drug. Uniform drug content was observed for all the formulations (99.43 ± 0.53% to101.54 ± 1.56%), which is as per the IP specification (90–110%) as shown in Table 5. The results of in vitro drug released at different time intervals is plotted against time to obtain the dissolution profiles as shown in Fig. 7. The dissolution profiles of candesartan phosphatase inhibitor library cilexetil from liquisolid tablets (LS 1 to LS 9) produced higher drug dissolution rate in comparison with the conventional tablets (CND) in 0.05 M phosphate buffer PH 6.5. It was apparent

that LS 7 formulation has the highest dissolution rate. The percentage of candesartan cilexetil dissolved from LS 7 reached 101.44% after only 30 min, while the CND had maximum candesartan cilexetil content (35.81%) dissolved after 30 min. While CND had a maximum drug released of 59.33% 60 min. The enhanced dissolution rates of liquisolid compacts

compared to CND may be attributed to the fact that, the drug is already in solution in Tween 80, while at the same time, it is carried by the powder particles (microcrystalline cellulose and BMN 673 silica). Thus, drug release is accelerated due to its markedly increased wettability and surface availability to the dissolution medium which is the proposed mechanisms for explaining the enhanced dissolution rate from the liquisolid compacts. Tween 80 facilitates wetting of drug particles by decreasing interfacial tension between dissolution medium and tablet surface.17 Surface response graph of the percentage drug released at 30 min was shown in Fig. 2(C). From the surface response Thymidine kinase graph it is clear that drug release is decreased with an increase in concentration of drug in liquid medication. Regression values of X1 and X2 for in vitro drug release at 30 min were as shown in Table 4.The drug release properties of liquisolid compacts were improved with increasing powder excipients ratio (R). Therefore, the liquisolid tablets with high R values and lower drug conc. in liquid medication i.e. LS7 showed maximal drug release at 30 min i.e.101.44% while that of LS 3 had minimum of 70.76% drug release at 30 min. One way ANOVA is applied for the angle of repose, disintegration time, and in vitro dissolution. Statistical significance of effect of all these dependent variables was done by comparing the mean square against an estimate of the experimental error.