Introduction:Bromhexine hydrochloride thins and loosens mucus to help clear stubborn chest congestion and breathing difficulties due to excess mucus in cold, flu and respiratory tract infections.The need for its gastro-retention is that it is dissolved in the pH range of 1-4 and after that its dissolution almost ceases because of the low solubility in the lower region of the gastrointestinal tract. The oral bioavailability of Bromhexine HCl is 20%. Thus, the floating drug delivery system may help Bromhexine HCl to stay in the acidic pH for long time and improve its oral bioavailability.Experimental:Floating tablets of Bromhexine HCl were prepared by using Thermoplastic Granulation technique.Different hydrophobic retardants were used namely carnauba wax,Hydrogenated Castor Oil and a hydrophilic polymer HPMC E15V were used in different combinations at different ratios for the preparation of the tablets. They were evaluated for tablet thickness, hardness, weight variation, friability, floating lag time and in-vitro drug release. Compatibility of the drug and polymers was assessed by Fourier transform infrared spectroscopy.Differential scanning calorimetry studies were also conducted.Results and Discussion:The λmax of Bromhexine HCl was found to be 248nm.FT-IR spectroscopy showed no interaction between the drug and polymers. DSC thermogram showed a sharp endothermic peak at 246 ºC which is corresponding to melting point of the drug. The in vitro drug release study of the gastro-retentive floating tablets of Bromhexine HCl was found to be 89.3% at the end of 12 hours for formulation 10.Conclusion:All the 12 formulations remained buoyant and showed drug release up to 12 hours.The use of hydrophobic retardants and hydrophilic polymer in combination had its own advantages of maintaining integrity and buoyancy of tablets. It could be concluded that for the proper floating duration and in vitro release, the hydrophobic retardants and hydrophilic polymer must be used in proper ratio. Formulation 10 was considered as the optimised formulation.

WHO biological expert published it Residual biological host cell DNA should not 10 ng per dose. As per recommendation by WHO Every commercial vaccine batches with compulsory required residual biological impurities specially Host cell DNA and Host cell Protein have mention result in Certificate of analysis and label claim to understand to common user . Because Impurity are critical harmful to human, Regulator have taken seriously Implementation of analysis of impurities for every commercial batch of vaccine ,Practically without analysis vaccine related residual biological impurities specially Host cell DNA and Host cell Protein is release to market . Host cell DNA Biological residual impurity should not 10 ng per dose .practically certificate of analysis vaccine quality control test is not covered ,easily analyst can analyze Host cell protein and DNA ,impurities but Vaccine specification test is not mentioned regulatory body have implement test for vaccine to avoid risk , It is observed chapter USFDA <1132> impurity profile qualification quantification acceptance limit it is pending to implement in 2017 by regulators, As early as possible vaccine specification to be include -USFDA chapter USFDA <1132>-IN FACT very important test Host cell DNA Biological residual impurity is MISSING in certificate of analysis of commercial batch of vaccine.

Doxorubicin (DOX) is a chemotherapeutic drug used for the treatment of a wide variety of cancers. It is known to cause cardiotoxicity. Gemcitabine (GEM) is an anticancer drug, but it has certain limitations like short biological half-life. A new paradigm to improve DOX and GEM therapeutic index is to administer them in nanoparticles (NPs). Nanoemulsions (NEs) are well-characterized NPs drug carriers that have been broadly implemented in the delivery of anticancer therapeutics. In this study, the antitumor activity of the combination formulas of GEM and DOX, either loaded in water (GEM+DOX-Sol) or NEs (GEM+DOX/LNE), were evaluated in Ehrlich ascites carcinoma (EAC) bearing swiss albino mice. The anticancer assessment of the NEs formulas in 200 mice divided into 10 groups included the detection of the change in body weight, hematological and serum biochemical profiles and studying the histopathological alterations of the heart, liver and kidney tissues. Results showed that mice treated with GEM+DOX/LNE, which has z-average 155.38 nm and zeta potential -38.5 mV, recorded a decrease in the mean tumor weight and significant increase in the cumulative mean survival time (MST), which was 60 days, as compared to the EAC control group, which has MST of 28 days. It also showed no significant changes in hematological and serum biochemical profiles compared to the normal group. In conclusion, the present study suggested that GEM treatment may significantly reduce cardiotoxicity induced by DOX in EAC-bearing mice. Also, GEM enhances the antitumor properties of DOX by increasing its inhibitory effect on tumor growth.

Acute myeloid leukemia (AML) is an aggressive disease in which the rapid growth of abnormal leukemic cells in bone marrow inhibits the production of normal blood cells. Genetic mutations, such as FLT3 and c-KIT, play their roles in the stepwise leukemogenesis. The most frequent mutations among AML are FLT3 mutations; however c-KIT mutations account for predicted higher relapse rate and less overall survival. Because development of point mutations or gene amplification of target proteins results in resistance of tyrosine kinase inhibitors, the use of a multi-targeted therapeutic approach is of potential clinical benefit. Several multi-targeted tyrosine kinase inhibitors have been developed toward clinical uses for treating AML, pancreatic cancer, non-small cell lung cancer, …etc. They showed inhibitions of ABL, FLT3, c-KIT, RET, PDGFR, SRC and VEGFRs, and an activity spectrum similar to tyrosine kinases-targeted drugs on the market. In the present study, a novel small molecular multi-targeted tyrosine kinase inhibitor DBPR487 was examined in in vitro kinase inhibition and cytotoxicity assays and evaluated for in vivo tumor growth inhibition efficacies. Furthermore, the plasma samples collected from the rats orally administered with DBPR487 were measured to determine the pharmacokinetic profile of DBPR487. Further preclinical toxicology and safety pharmacology studies are undergoing toward clinical development.

Statement of the Problem: Around 40% of new chemical entities (NCE’s) are poorly water soluble and not well absorbed after oral administration. To overcome the problems associated with oral absorption and bioavailability of these poorly soluble drugs, various strategies have been utilized out of which hydrotropic solubilization has shown promising results. The present study was undertaken on Indomethacin - a water insoluble drug to enhance its solubility using mixed hydrotropic solubilization technique followed by development and validation of UV spectrophotometric method for quantitative estimation of Indomethacin in bulk and pharmaceutical dosage forms. Methodology: Preliminary solubility studies were carried out with different molars of hydrotropic agents and from the solubility studies performed, proper blend (1.5 M Sodium citrate and 1.5 M Sodium benzoate) of hydrotropic agents was selected for further study. UV spectrum and calibration curve of Indomethacin was established in selected blend of hydrotropic agents and it was found to exhibit λmax of 320 nm. Analysis of bulk drug of Indomethacin and marketed samples in chosen blend of hydrotropic agents was done and total drug content was calculated. The developed method was then validated as per ICH guidelines for Linearity and range, Accuracy, Precision, Limit of detection (LOD) and limit of quantification (LOQ). Findings: From the results, it was clear that there was significant increase in solubility of Indomethacin with increase in molarity of hydrotropic agents and a blend of 1.5 M Sodium citrate and 1.5 M Sodium benzoate showed good results. Conclusion and significance: Thus it was concluded mixed hydrotropic solubilisation can be effectively used for solubility enhancement of poorly water soluble drugs and the proposed UV method which is new, simple, accurate and reproducible can be successfully employed for the routine analysis of Indomethacin in bulk samples as well as other pharmaceutical dosage forms.

Alpinia galanga, an important edible plant in Family Zingiberaceae, is commonly used in Asian folk medicinal remedies. The essential oil of A. galanga rhizomes (AGO) has many biological activities e.g. antioxidant, antibacterial, antifungal, and anti-inflammatory actions. However, the poor water miscibility of AGO causes the limitation of its clinical use in both human and animals. The alcohol used to dissolve AGO for fish anesthesia always causes hyperactivity in fish. The aim of this study was to solve this problem by developing self-microemulsifying drug delivery systems (SMEDDS) of AGO. Pseudoternary phase diagrams of AGO were constructed to identify the best AGO-SMEDDS formulation. It was found that the AGO-SMEDDS composed of 20.0% AGO and 53.3% Tween 80 and 26.7% ethanol had a mean droplet size of 82 nm after dispersing in distilled water. The anesthetic activity of the developed AGO-SMEDDS in koi (Cyprinus carpio) was evaluated in comparison with an AGO ethanol solution on the induction time required to reach the surgical anesthetic stage in which the fish stop all swimming activity and show loss of equilibrium and responsiveness. Results showed that the induction times of the fish receiving 200, 300, and 400 mg/L AGO-SMEDDS were 233, 130, and 112 sec, respectively. Importantly, AGO-SMEDDS showed significantly higher anesthetic activity than the AGO ethanol solution which showed the induction times of 303, 207, and 167 sec, with the same dose of AGO, respectively. The transportation pathway of AGO was investigated using a fluorescence microscope. AGO was labeled with nile red. The brain, gills, and skin of fish showed red fluorescent spots without autofluorescence phenomena compared to unlabeled AGO. This result suggests that the AGO entered the fish via gills and skin and was transported to the brain where the anesthetic effect took place.