Synthesis, Characterization and Quantification of Simvastatin Metabolites and Impurities

Simvastatin is used in treatment of hypercholesterolemia because it regulates cholesterol synthesis as a result of its β-hydroxy acid acting as an inhibitor of 3-hydroxy-methylglutaryl coenzyme A (HMG-CoA). The present communication deals with synthesis, characterization and development of accurate, precise and sensitive Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method for simultaneous estimation of simvastatin and its synthetic impurities. The impurities methyl ether and β-hydroxy acid of simvastatin were synthesized in the laboratory and characterized by MS, NMR and FT-IR spectroscopy. The separation of simvastatin and its impurities was carried out on an isocratic JASCO RP-HPLC system using KYA TECH HIQ SIL C18 column (150 × 4.6 mm internal diameter, particle size 5 μm) operating at ambient temperature using acetonitrile:water (80:20 v/v) with 0.1% orthophosphoric acid as mobile phase. The method developed for HPLC analysis of three impurities along with simvastatin was validated using ICH Q2B (R1) guidelines and it complied with these guidelines. The results of analysis were found to be in the range of 98.14% to 101.89% for all analytes with acceptable accuracy and precision. The method can be used for detection and quantification of synthetic impurities in bulk or formulations of simvastatin

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Implications of formulation design on lipid-based nanostructured carrier system for drug delivery to brain

<p><i>Context & Objective</i>: The aim of present investigation was to formulate and develop lipid-based nanostructured carriers (NLCs) containing Idebenone (IDE) for delivery to brain. Attempts have been made to evaluate IDE NLCs for its pharmacokinetic and pharmacodynamic profile through the objective of enhancement in bioavailability and effectivity of drug.</p> <p><i>Methods</i>: Nanoprecipitation technique was used for development of drug loaded NLCs. The components solid lipid Precirol ATO 5, oil Miglyol 840, surfactants Tween 80 and Labrasol have been screened out for formulation development by consideration of preformulation parameters including solubility, Required Hydrophilic lipophilic balance (HLB) of lipids and stability study. Developed IDE NLCs were subjected for particle size, zeta potential, entrapment efficiency (%EE), crystallographic investigation, transmission electron microscopy, <i>in vitro</i> drug release, pharmacokinetics, <i>in vivo</i> and stability study.</p> <p><i>Results</i>: Formulation under investigation has particle size 174.1 ± 2.6 nm, zeta potential −18.65 ± 1.13 mV and% EE 90.68 ± 2.90. Crystallographic studies exemplified for partial amorphization of IDE by molecularly dispersion within lipid crust. IDE NLCs showed drug release 93.56 ± 0.39% at end of 24 h by following Higuchi model which necessitates for appropriate drug delivery with enhancement in bioavailability of drug by 4.6-fold in plasma and 2.8-fold in brain over plain drug loaded aqueous dispersions. <i>In vivo</i> studies revealed that effect of drug was enhanced by prepared lipid nanocarriers.</p> <p><i>Conclusions</i>: IDE lipid-based nanostructured carriers could have potential for efficient drug delivery to brain with enhancement in bioavailability of drug over the conventional formulations.</p

RP-HPLC and Spectrophotometric Estimation of Ambroxol Hydrochloride and Cetirizine Hydrochloride in Combined Dosage Form

Rapid, precise, accurate, specific and sensitive reverse phase liquid chromatographic and absorbance ratio spectrophotometric methods have been developed for the simultaneous analysis of ambroxol hydrochloride and cetirizine hydrochloride in their tablet formulation. The chromatographic methods were standardized using a HIQ SIL-C18 column (250×4.6 mm i.d., 10 μm particle size) with UV detection at 229 nm and mobile phase consisting of methanol-acetonitrile-water (40:40:20, v/v/v). Ambroxol hydrochloride and cetirizine hydrochloride have absorbance maxima at 243 nm and 229 nm, respectively. The isoabsorptive wavelength for both the drugs was 236 nm. For absorbance ratio method developed, wavelengths selected were 243 nm and 236 nm. The proposed methods were successfully applied to the determination of ambroxol hydrochloride and cetirizine hydrochloride in tablets, with high percentage of recovery, good accuracy and acceptable precision. Different analytical performance parameters such as linearity, precision, accuracy, limit of detection, limit of quantitation and robustness were determined according to International Conference on Harmonization ICH Q2B guidelines. Results of analysis of the developed method were compared by performing ANOVA

3D QSAR ANALYSIS OF 2,4-DISUBSTITUTED 1,5-BENZODIAZEPINE DERIVATIVES AS CNS DEPRESSANTS

New 2,4-disubstituted-1,5-benzodiazepine derivatives containing different functional groups have been screened for their CNS depressant activity. The synthesized benzodiazepine derivatives were screened for CNS depressant activity using the actophotometer model for mice. QSAR studies of synthesized derivatives were performed on Vlife MDS 3.5 software. The data set for QSAR studies encompassed activities of 45 molecules and 252 descriptors calculated by Vlife MDS 3.5. The training set comprised of 36 molecules and test set of 9 molecules. QSAR equation revealed that some electronic, steric and liphophillic parameters have correlation with CNS depressant activity. The best equation was selected on basis of correlation coefficient (r 2 ) and predicitivity of equation

Pharmacophore modeling and 3D QSAR studies of aryl amine derivatives as potential lumazine synthase inhibitors

Design and discovery of novel antifungal compounds is the need of time, more than ever before due to the unavailability of effective antifungal therapy to treat resistant fungal infections. Due to morphological and functional similarities of fungi both with plant cell and human cell, the search for effective targets leading to specificity of antifungal drug action becomes all that more difficult. For the design of novel antifungal agents, it is necessary to comprehend the life cycle, morphology, metabolic pathways, etc. of fungi scientifically and systematically to identify critical targets for antifungal drug design. Fungi specific riboflavin metabolism involves lumazine synthase catalyzed synthesis of 6,7-dimethyl-8-D-ribityl lumazine which is converted to riboflavin by a riboflavin synthase. Therefore lumazine synthase has been targeted for the design of newer antifungal agents. The pharmacophore modeling and 3D QSAR studies were carried out on 32 N-substituted aryl amine derivatives as fungal lumazine synthase inhibitors. The selected model of 3D QSAR showed positive correlation of electronic descriptors with antifungal activity while steric and hydrophobic descriptors showed negative correlation with antifungal activity. The resulting model exhibited good q2 and r2 values up to 0.9109 and 0.845 respectively

Expulsion by Ionic Complexation: Benchmark Therapy for Atherosclerosis A Review

Ethylenediamine tetraacetic acid (EDTA) chelation therapy has been practiced since longtime for the treatment of cardiovascular diseases, alone or in combination with other treatments. It has been recommended as a harmless, relatively inexpensive and non-surgical method of restoring blood flow in atherosclerotic vessels. Ability of EDTA to form complex with heavy metals like calcium, lead, copper is used to remove calcium from arthrosclerosis plaques which ultimately improves the condition. It can be concluded that chelation therapy is emerging form of complementary or alternative medicine to surgery and can be used in safe manner. Still there is insufficient evidence to decide on the effectiveness or ineffectiveness of chelation therapy in improving clinical outcomes of patients with atherosclerotic cardiovascular disease