Glucosamine HCl-based solid dispersions to enhance the biopharmaceutical properties of acyclovir

The objective of the work presented here was to assess the feasibility of using glucosamine HCl as a solid-dispersion (SD) carrier to enhance the biopharmaceutical properties of a BCS class III/IV drug, acyclovir (ACV). The solid-dispersions of acyclovir and glucosamine HCl were prepared by an ethanol-based solvent evaporation method. The prepared formulations characterized by photomicroscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transforms infrared spectrophotometry (FTIR), powder x-ray diffractometry (PXRD) and drug content analysis. The functional characterization of ACV-SD was performed by aqueous solubility evaluation, dissolution studies, fasted versus fed state dissolution comparison, ex vivo permeability, and stability studies. Photomicroscopy and SEM analysis showed different surface morphologies for pure ACV, glucosamine HCl and ACV-SD. The physical-chemical characterization studies supported the formation of ACV-SD. A 12-fold enhancement in the aqueous solubility of ACV was observed in the prepared solid dispersions, compared to pure ACV. Results from in vitro dissolution demonstrated a significant increase in the rate and extent of ACV dissolution from the prepared ACV-SD formulations, compared to pure ACV. The rate and extent of ACV permeability across everted rat intestinal membrane were also found to be significantly increased in the ACV-SD formulations. Under fed conditions, the rate and extent of the in vitro dissolution of ACV from the formulation was appreciably greater compared to fasted conditions. Overall, the results from the study suggest the feasibility of utilizing glucosamine HCl as a solid dispersion carrier/excipient for enhancement of biopharmaceutical properties of acyclovir, and similar drugs with low solubility/permeability characteristics

Prediction of peptidoglycan hydrolases- a new class of antibacterial proteins

Comparison of performance of the three approaches using known 250 peptidoglycan hydrolases. (XLSX 8 kb

Novel Psychoactive Substances 14Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs

A feature of human culture is that we can learn to consume chemical compounds, derived from natural plants or synthetic fabrication, for their psychoactive effects. These drugs change the mental state and/or the behavioral performance of an individual and can be instrumentalized for various purposes. After the emergence of a novel psychoactive substance (NPS) and a period of experimental consumption, personal and medical benefits and harm potential of the NPS can be estimated on evidence base. This may lead to a legal classification of the NPS, which may range from limited medical use, controlled availability up to a complete ban of the drug form publically accepted use. With these measures, however, a drug does not disappear, but frequently continues to be used, which eventually allows an even better estimate of the drug 19s properties. Thus, only in rare cases, there is a final verdict that is no more questioned. Instead, the view on a drug can change from tolerable to harmful but may also involve the new establishment of a desired medical application to a previously harmful drug. Here, we provide a summary review on a number of NPS for which the neuropharmacological evaluation has made important progress in recent years. They include mitragynine ( 1CKratom 1D), synthetic cannabinoids (e.g., 1CSpice 1D), dimethyltryptamine and novel serotonergic hallucinogens, the cathinones mephedrone and methylone, ketamine and novel dissociative drugs, ;3-hydroxybutyrate, ;3-butyrolactone, and 1,4-butanediol. This review shows not only emerging harm potentials but also some potential medical applications

A VALIDATED LC-MS/MS METHOD FOR PHARMACOKINETIC STUDY OF CANAGLIFLOZIN IN HEALTHY RABBITS

Objective: A liquid chromatography-tandem mass spectrophotometric (LC-MS/MS) method was developed for quantification of canagliflozin in rabbit plasma employing Liquid-Liquid extraction technique.Methods: Chromatographic separation was achieved on Inertsil ODS 5 µm C18, 50×4.60 mm with 30:70 v/v of 0.01M ammonium acetate: methanol as an isocratic mobile phase with a flow rate of 0.8 ml/min. The developed LC-MS method was applied to assess Cmax, t1/2, AUC0-t, and AUC0-inf of canagliflozin tablet after oral administration in healthy rabbits.Results: The developed method was linear over working range of 5ng/ml to 600ng/ml with a coefficient of correction (r2) = 0.999. The % recovery of the method was found to be 102.05%. The mean intraday and inter-day precision of the method was found to be 0.77 to 3.72%. The Canagliflozin showed Tmax of 1.58±0.2 and mean Cmax, AUC0®t andAUC0®a for Test formulation is 272±13.24, 2571.20±251and 2777.43±276 respectively.Conclusion: The developed method can be applied for routine analysis for quality control and the established LLOQ is sufficiently low to conduct a pharmacokinetic study with any marketing formulation of Canagliflozin in healthy rabbits

A UPLC-MS/MS METHOD DEVELOPMENT AND VALIDATION FOR THE ESTIMATION OF SOFOSBUVIR FROM HUMAN PLASMA

Objective: The present work aimed to develop a simple, rapid, specific and precise ultra-performance liquid chromatography-tandem mass spectrophotometric (LC–MS/MS) validated method for quantification of sofosbuvir and internal standard (ISTD) Sofosbuvir-d3 in human plasma.Methods: Samples prepared by employing liquid-liquid extraction (LLE) using 2.5 ml of ethyl acetate. Chromatographic separation was achieved on Gemini 5µ C18, 50 x 4.6 mm column using a mixture of 0.1% (v/v) formic acid in water to methanol at a ratio of 30:70 v/v as the mobile phase. The flow rate was 0.50 ml/min. The LC eluent was split, and approximately 0.1 ml/min was introduced into Tandem mass spectrometer using turbo Ion Spray interface at 325 °C. Quantitation was performed by transitions of 428.35/279.26 (m/z) for sofosbuvir and 431.38/282.37 (m/z) for sofosbuvir-d3.Results: The concentrations of ten working standards showed linearity between 4.063 to 8000.010ng/ml (r2 ≥ 0.9985). Chromatographic separation was achieved within 2 min. The average extraction recoveries of three quality control concentrations were 75.36% for sofosbuvir and were within the acceptance limits. The coefficient of variation was ≤15% for intra-and inter-batch assays. The %CV of ruggedness ranges 0.35% and 3.09%. The % stability of short term and long term stock solution stability studies was found to be 97.25% and 98.81% respectively.Conclusion: The results obtained for specificity, linearity, accuracy, precision, ruggedness and stability studies were within the acceptance limits. Thus the validated economical method was applied for pharmacokinetic studies of sofosbuvir

A medical student elective promoting humanism, communication skills, complementary and alternative medicine and physician self-care: an evaluation of the HEART program.

ObjectiveIn 2002 the American Medical Student Association (AMSA) created a fourth-year medical student elective known as the Humanistic Elective in alternative medicine, Activism, and Reflective Transformation (HEART) that provided the opportunity for students to explore humanism in medicine, self-care, complementary and alternative medicine modalities, communication, activism, and community building in a four-week immersion experience. The educational effects of this elective, and whether it has met its stated goals, are unknown.MethodThe authors conducted a web-based, cross-sectional survey of the first eight cohorts of HEART graduates in 2010. Survey questions assessed respondents' demographics and perspectives on the educational impact of the elective. Descriptive statistics were used to characterize the sample and qualitative analyses were guided by grounded theory.ResultsOf 168 eligible alumni, 122 (73%) completed the survey. The majority were female (70%), age ≤35 (77%) years, and trained in primary care specialties (66%). Half were attendings in practice. The majority of respondents felt the elective taught professionalism (89%) and communication skills (92%) well or very well. The majority highly agreed that the elective helped them better cope with stress during residency training (80%), taught them self-care skills (75%), and improved their ability to empathize and connect with patients (71%). Qualitative analysis of the personal and professional impact of the elective identified twelve common themes with self-discovery, self-care, and collegial development/community most frequently cited.ConclusionsThe majority of HEART graduates endorse learning important skills and benefiting from the experience both personally and professionally. Aspects of the HEART curriculum may help training programs teach professionalism and improve trainee well-being

Antimicrobial effects of Citrus sinensis peel extracts against dental caries bacteria: an in vitro study

Background: Ethnomedicine is gaining admiration since years but still there is abundant medicinal flora which is unrevealed through research. The study was conducted to assess the in vitro antimicrobial potential and also determine the minimum inhibitory concentration (MIC) of Citrus sinensis peel extracts with a view of searching a novel extract as a remedy for dental caries pathogens. Material and Methods: Aqueous and ethanol (cold and hot) extracts prepared from peel of Citrus sinensis were screened for in vitro antimicrobial activity against Streptococcus mutans and Lactobacillus acidophilus , using agar well diffusion method. The lowest concentration of every extract considered as the minimal inhibitory concentration (MIC) values were determined for both test organisms. One way ANOVA with Post Hoc Bonferroni test was applied for statistical analysis. Confidence level and level of significance were set at 95% and 5% respectively. Results: Dental caries pathogens were inhibited most by hot ethanolic extract of Citrus sinensis peel followed by cold ethanolic extract. Aqueous extracts were effective at very high concentrations. Minimum inhibitory concentration of hot and cold ethanolic extracts of Citrus sinensis peel ranged between 12-15 mg/ml against both the dental caries pathogens. Conclusions: Citrus sinensis peels extract was found to be effective against dental caries pathogens and contain compounds with therapeutic potential. Nevertheless, clinical trials on the effect of these plants are essential before advocating large-scale therap

Pseudomonas septicaemia: in a case of pancytopenia

Pseudomonal infection is a rare condition with multiple systemic complications. A new condition of interest is ecthyma gangrenosum in a patient with pseudomonas septicaemia with pancytopenia and megaloblastic anaemia. So here we present you the case of Ecthyma gangrenosum in a 20-year-old female with pseudomonas septicaemia due to pancytopenia. A high degree of clinical suspicion is required, but a tissue sample is ultimately necessary for definitive diagnosis

The study of outcome in fractures of proximal third of tibia in adults treated by expert tibia nail

This study aims to evaluate the clinical, functional outcome and complications of fracture proximal third of tibia treated with expert tibia nail in terms of radiological union, functional outcomes by short form -36 (SF-36) score, Johner and Wruhs criteria, visual analogue score and patient satisfaction score. Twenty-five patients with fracture proximal third of tibia treated with expert tibia nail in SNMC and HSK hospital and research centre, Bagalkot were enrolled in this study. The radiological union was assessed by plain radiograph and functional outcome by SF-36 score, Johner and Wruhs criteria, visual analogue score and patient satisfaction score. The radiological union was achieved in all the patients between 14 to 26 weeks duration (mean of 19.6±2.82 weeks). The mean SF-36 score was 84.9±4.06 and the mean visual analogue score was 2±1.78 at the 22nd week of follow-up. Results based on Johner and Wruhs criteria, 17 patients had excellent, 6 had good, 1 had fair and 1 had poor results. The average patient satisfaction score was 8.88 out of 10. There were 8 cases of post-operative knee pain, 5 cases of infection, 2 cases of malunion, 1 case of shortening and 1 case of the delayed union in our study. Intramedullary fixation with expert tibia nail for fracture proximal third tibia is a safe and less invasive technique. The radiological union was achieved in all the cases. This technique ensures excellent functional outcomes and a low incidence of complications

Sentiment Analysis on IMDb Movie Reviews Using Hybrid Feature Extraction Method

Social Networking sites have become popular and common places for sharing wide range of emotions through short texts. These emotions include happiness, sadness, anxiety, fear, etc. Analyzing short texts helps in identifying the sentiment expressed by the crowd. Sentiment Analysis on IMDb movie reviews identifies the overall sentiment or opinion expressed by a reviewer towards a movie. Many researchers are working on pruning the sentiment analysis model that clearly identifies and distinguishes between a positive review and a negative review. In the proposed work, we show that the use of Hybrid features obtained by concatenating Machine Learning features (TF, TF-IDF) with Lexicon features (Positive-Negative word count, Connotation) gives better results both in terms of accuracy and complexity when tested against classifiers like SVM, Naïve Bayes, KNN and Maximum Entropy. The proposed model clearly differentiates between a positive review and negative review. Since understanding the context of the reviews plays an important role in classification, using hybrid features helps in capturing the context of the movie reviews and hence increases the accuracy of classification