Solubility Enhancement of Ebastine by Formulating Microemulsion Using D-Optimal Mixture Design: Optimization and Characterization.

Ebastine, a histamine H1 antagonist, nonsedating, belonging to BCS class II is used in the treatment of allergic rhinitis and chronic idiopathic urticaria. The current study was intended in augmenting the aqueous solubility and dissolution rate of ebastine, by formulating a microemulsion system using oleic acid, Transcutol® HP, and Tween®80 as oily phase, cosurfactant, and surfactant, respectively, by the phase titration method. A custom mixture design with optimality D was used to design the formulation by using the Design Expert® Software (Version 11; Stat-Ease, Inc., Minneapolis, MN, USA). Optimization of formulation was performed using the numerical optimization technique, where optimization is based upon the desirability. The optimized formulation was evaluated for transmittance, viscosity, globule size, polydispersity index, zeta potential, drug content, morphological studies, and in vitro studies. The optimized formulation displayed percent cumulative drug release, ranging from 82.9% to 90.6% obtained after dissolution studies and the percent cumulative drug release after diffusion studies ranged from 83.3% to 100%. The in vitro release data were subjected to kinetic treatment. The zero-order and first-order plots were linear and showed the highest values for R2, which indicated mixed-order release. The Higuchi plot was linear, indicating diffusion as the mechanism of release. From Peppas plot, it was further confirmed that the release for dissolution studies was anomalous and for diffusion studies it was zero order. Thus, the studies concluded that the microemulsion technique is a very good approach for enhancing the solubility and dissolution rate of the BCS class II drug ebastine.

Correlation of obesity indices with heart rate recovery as a marker of autonomic function in healthy young adults.

INTRODUCTION: Obesity has become a challenge for global public health. The global prevalence of obesity has nearly doubled in the past decades (World Health Organization). Obesity may lead to changes in the sympathetic regulation of cardiovascular function, thus favoring the development of cardiovascular complications. AIM: To find a correlation between various obesity indices (body mass index, waist-height ratio, waist circumference and waist-hip ratio) and heart rate recovery in healthy subjects. MATERIALS AND METHODS: A total of 100 apparently healthy subjects aged 18-30 years were enrolled and were divided into two groups on the absence and presence of a family history of cardiovascular disease. The treadmill testing was done in the exercise lab of the physiology department of the medical institute. Exercise testing of the subjects was conducted according to the standard Bruce protocols. RESULTS: There was a negative correlation between various obesity indices and heart rate recovery but we did not get a statistically signification association between them. CONCLUSION: In our study, we have found no statistically significant association between various obesity indices and heart rate recovery. Thus measuring obesity indices in the younger age group will not lead to much significance in terms of heart rate recovery and may be avoided.

Hit identification and drug repositioning of potential non-nucleoside reverse transcriptase inhibitors by structure-based approach using computational tools (part II).

AIDS is a global infection involving several complications and its increasing prevalence every year has prioritized our study. Therapy associated with HIV has led to emergence of multidrug resistance and toxicity. Thus, the development of a potent, affordable and safe anti-HIV drug is a global concern. Among the different targets developed, inhibition of non-nucleoside reverse transcriptase (NNRT) is found to be effective and promising. Etravirine, efavirenz, nevirapine, rilpivirine and delavirdine are the marketed NNRTIs available. This study is focused on computational prediction of hit molecules as well as repurposing of various FDA-approved drugs as potential NNRTIs. A synthetic database from ZINCpharmer, publicly available natural databases of coumarins, chromones and chalcones, and two databases of FDA-approved drugs for repurposing were screened to check for the possibility of these compounds to possess anti-HIV activity. Study utilizes a structure-based approach with the generated pharmacophore of target protein (PDB ID: 3MEC), screening of selected datasets is carried out using the Phase tool of Schrodinger. The top filtered compounds with good fitness score were proceeded to molecular docking studies to study their binding affinity to the target. Energy-based calculations using Prime MM-GBSA of Schrodinger was performed to determine free binding energy of the complexes. Prediction of pharmacokinetic parameters of top compounds is further carried out and reported. All the results obtained from different databases are compiled, interpreted and five molecules were subjected to molecular dynamic studies to further confirm the prediction and identified hit molecules for in vitro screening as potential NNRTIs.Communicated by Ramaswamy H. Sarma.

Design of metronidazole derivatives and flavonoids as potential non-nucleoside reverse transcriptase inhibitors using combined ligand- and structure-based approaches.

Acquired Immuno Defficiency Syndrome (AIDS) is one of the major global life threatening condition caused by Human Immunodeficiency Virus (HIV) and its prevalence has been increasing every year. Hence, this study has put its emphasis on HIV. Inhibition of Non-Nucleoside Reverse Transcriptase (NNRT) is considered as a well-developed target for HIV. Structure-based pharmacophore model was generated using the Phase tool of Schrodinger and screened database of metronidazole derivatives, flavonoids and metronidazole-flavonoid hybrid molecules. Compounds having good fitness score with similar pharmacophoric features as that of the Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) in market or clinical trials and metronidazole derivatives with reported anti-HIV activity are taken for molecular docking and rescoring by Glide and Prime tools. Hybrid molecules demonstrated good docking score and similar binding interactions as that of reference drugs. From Prime MM-GBSA rescoring, free binding energy was found less and protein-ligand complexes were stabilized with van der Waals free energy and nonpolar solvation terms. Further, atom-based QSAR model of reported metronidazole derivatives as NNRTIs was developed with good statistical values to further refine the database. Pharmacokinetic and toxicity prediction of the top compounds using some free wares like pkCSM and SwissADME reported that identified top compounds have good ADMET profile for oral administration, safe excretion and less toxicity. Study suggests that metronidazole-flavonoid hybrid molecules can be taken as lead molecule for further biological screening and has scope in future drug discovery as safe and potential NNRTIs.Communicated by Ramaswamy H. Sarma.

Metabolic flux network analysis of hydrogen production from crude glycerol by Clostridium pasteurianum.

The present study has attempted to get insight into ultrasound induced enhancement in biohydrogen production from glycerol fermentation using metabolic flux analysis (MFA). A pseudo steady state metabolic flux network model was constructed and analyzed using experimentally measured glycerol uptake rate and fluxes of four metabolites, viz. acetate, butyrate, succinate and 1,3-PDO. Glycerol consumption increased by ∼50% under sonication. Biohydrogen yield showed marked rise of ∼40% with application of ultrasound. Butyrate and 1,3-PDO were the major products of glycerol metabolism. Sonication had major influence on carbon fluxes at the acetyl-CoA node. MFA results revealed enhanced flux towards butyrate under sonication, which was manifested in higher butyrate to acetate (B/A) ratio in products and greater H2 generation. Biohydrogen production was also a microbial growth associated process. Finally, two theoretical alternatives for further enhancement of biohydrogen production were assessed with MFA, viz. enhancement of glycerol uptake and blocking of butyrate pathway.