A SIMPLE AND RUGGED BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF BRIVUDINE IN HUMAN PLASMA BY USING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY

Objective: The current research work focus to simple and rugged bioanalytical method development and validation of brivudine in human plasma using high-performance liquid chromatography. Methods: The analyte (Brivudine) and internal standard (Sofosbuvir) were extracted using the Solid Phase Extraction (SPE) technique. The chromatographic separation was accomplished by using Zorbax eclipse XDB-C18 Column (150×4.6 mm, 5 μm) with a mobile phase consisted of Methanol: 0.5% Ortho-phosphoric acid (65:35%, v/v) respectively, at a flow rate of 0.7 mL/min. The developed method was validated by performing system suitability, carryover effect, linearity, selectivity, sensitivity, precision, accuracy, recovery, ruggedness, and stability studies. The method was validated as per USFDA guidelines. Results: The selected chromatographic condition was found to efficiently separated brivudine (RT-3.55 min) and ISTD (RT-7.87 min). The assay demonstrated a linear dynamic range of 85.205 to 4500.246 ng/ml for brivudine in human plasma with r2>0.99. Demonstrated the lowest limit of detection at 85.205 ng/ml. This method established an intra-run and inter-run precision within the range of 2.99-6.31%CV and 3.67-5.80%CV, respectively. Additional intra-run and inter-run accuracy were within the range of 97.55-105.37% and 99.27-102.15%, respectively. The mean percentage recovery of brivudine and ISTD studies proved good extraction efficiency and the robustness was also evaluated. Conclusion: A simple, accurate, precise, linear and rugged RP-HPLC method was developed and validated for the estimation of brivudine in human plasma with K2EDTA anticoagulant and suitable for conducting BA/BE and TDM

BIOANALYSIS METHOD DEVELOPMENT AND VALIDATION OF SMALL MOLECULES IN PHARMACEUTICAL INDUSTRY: A BIOANALYST REVIEW POINT

The focus of bioanalysis employed for the quantitative determination of an active analyte(s) and their metabolite(s) in the biological matrix such as plasma, serum, blood, cerebrospinal fluid, and tissues. The extraction of analyte and metabolite in the biological fluids is carried out using different separation methods such as protein precipitation, liquid-liquid extraction, and solid phase extraction. Bioanalytical method development and validation in the pharmaceutical industry are to provide an assessment and interpretation of pharmacokinetics, pharmacodynamics, toxicokinetics, bioavailability/bioequivalence, and therapeutic drug monitoring relationships. This review paper aims to provide a simple and accurate scientific background to improve the quality for development and validation of a bioanalytical method for small molecules with industrial technique as per regulatory agency requirements (United States Food and Drug Administration, EMEA, International Council for Harmonisation and ANVISA)

BIO-ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR THE SIMULTANEOUS ESTIMATION OF DECITABINE AND CEDAZURIDINE IN HUMAN PLASMA USING LC-MS/MS

Objective: The present work aimed to develop a novel, reliable and accurate Liquid Chromatography-Mass Spectrometry/Mass spectrometry (LC-MS/MS) method for the simultaneous quantification of Decitabine and Cedazuridine a combined medication used for the treatment of chronic myelomonocytic leukemia in human plasma. Methods: Talazoparib drug is used as an internal standard in the study. Both the analytes and internal standard were isolated from 100 ml plasma samples by liquid-liquid extraction and then chromatographed on Zorbax SB-CN (4.6 mm×75 mm, 3.5 µm) column with a mobile phase consisting of 0.1 % ammonium formate and methanol in the ratio of 65:45 (v/v) pumped at 0.5 ml/min. The method had a chromatographic total run time of 5 min. Results: The developed method gave a symmetric peak at a retention time of 1.7 min for Decitabine, 2.2 min for Cedazuridine, 3.5 min for Talazoparib and satisfied all the peak properties as per USP guidelines. The mass spectral characterization of separated analytes in the LC method was performed using a mass detector operated at Multiple Reaction Monitoring mode with precursor-to-product ion transitions at m/z of 229 to m/z of 114 as MH+ion for Decitabine, m/z of 269 to m/z of 118 as MH+ion for Cedazuridine. A very sensitive limit of detection of 0.3 ng/ml was observed and showed a calibration curve linear over the concentration range of LLOQ (lower limit of quantification) to 500 ng/ml. The other validation parameters were found to have acceptable accuracy, precision, linearity, and selectivity. The mean extraction concentration was acceptable and very high for both the analytes in HQC (high-quality control concentration), MQC (medium quality control concentration) and LLOQ levels. The peak area response ratio of Decitabine and Cedazuridine with the internal standard in freeze-thaw, short term and long term stability studies was found to be acceptable confirms that the method is stable. Conclusion: It can be concluded that the proposed method is specific, accurate, and precise and could be used for the simultaneous estimation of Decitabine and Cedazuridine in human plasma

FORMULATION AND EVALUATION OF MICROEMULSION GEL FOR TRANSDERMAL DELIVERY OF TRAMADOL

Objective: The present work was carried out to design microemulsion gel system for transdermal delivery of the drug to minimize the side effects and to reduce the frequency of administration and for prolonging the duration of action. Methods: Tramadol, an opioid analgesic drug, was mixed with various selected polymers such as sodium alginate (SA), acacia, hydroxypropyl methylcellulose (HPMC), and Eudragit in geometric mixing ratios. The drug, polymer, and other excipients were mixed thoroughly by trituration method and different formulations (F1-F8) were prepared the same quantity of all the ingredients excepting the polymers. Results: The different formulations prepared, studied, and showed that the formulation using SA as polymeric carrier had a better effect on the evaluated parameters. The drug-SA formulation exhibited better drug-polymer compatibility, optimal viscosity (2750 cps), zeta potential (−26.1 Mv), and particle size distribution (262.8 d.nm) values. The in vitro release studies also indicated that the drug-SA formulation was of desirable release pattern, thus indicating that SA to be a better choice in formulating a transdermal delivery gel system. Conclusion: Evaluated microemulsion gel formulation F2 of tramadol with polymeric carriers SA was much stable than other carriers used. Thus, it could be concluded that the gel formulation with SA can be taken as an ideal formulation

Development And Evaluation Of Colon Targeted Drug Delivery For Mesalamine

The main objective of this study was to formulate mesalamine loaded alginate microspheres for local treatment of ulcerative colitis and optimized batch were then filled in capsules coated with Eudragit S 100. The microspheres were prepared by ionic gelation method. Box Behnken design using design expert software was employed in formulating and optimizing the microspheres. Microspheres were evaluated for particle size, shape and entrapment efficiency. The optimized batch was then filled in capsule coated with Eudragit S100.This encapsulated system released alginate microspheres at colon region in a sustained manner. The drug release of microspheres showed a longer residence time in the colon due to better mucoadhesion properties of sodium ALG. Therefore mesalamine-loaded alginate microspheres enteric coated in capsules can be potential delivery system for local treatment of ulcerative coliti

Development and characterization of controlled release mucoadhesive tablets of captopril

El estudio actual trata del desarrollo de los comprimidos mucoadhesivos de captopril, que se diseñaron con el fin de prolongar el tiempo de permanencia gástrica después de la administración oral. Se formularon matrices de comprimidos de captopril mediante diferentes polímeros mucoadhesivos, tales como goma guar, goma xantana, hidroxipropilmetilcelulosa K4M y K15M, a varias concentraciones. Los comprimidos se evaluaron según sus propiedades físicas, uniformidad del contenido, índice de inflamación, fuerza de bioadhesión y liberación farmacológica in vitro. La inflamación se incrementó cuando la concentración y la viscosidad de HPMC aumentaron. Los comprimidos formulados solamente con goma guar y goma xantana se descompusieron con mayor rapidez y se disolvieron completamente en un rango de 5-7 horas, mientras que los comprimidos con HPMC permanecieron intactos y mostraron una liberación lenta de hasta 11-12 horas. Se observó que la formulación F10 con HPMC K15M y goma xantana (1:1) tenía una fuerza bioadhesiva máxima de 31,59±0,05 g y la liberación farmacológica in vitro fue del 91,85%, al final de un periodo de 12 horas con un mecanismo de difusión no de Fick. Los estudios de estabilidad de lotes optimizados mostraron que no hay cambios en la fuerza bioadhesiva y la liberación in vitro cuando se mantiene bajo condiciones de diferentes temperaturas durante 60 días. Se concluyó que la formulación F10 presenta la mejor fuerza bioadhesiva y liberación farmacológica.The present investigation concerns the development of mucoadhesive tablets of Captopril which were designed to prolong the gastric residence time after oral administration. Matrix tablets of Captopril were formulated using different mucoadhesive polymers such as guar gum, xanthan gum, hydroxyl propyl methyl cellulose K4M and K15M in various ratios. The tablets were evaluated for physical properties, content uniformity, swelling index, bioadhesive strength and in-vitro drug release. Swelling was increased as the concentration and viscosity of HPMC increases. Tablets formulated using guar gum and xanthan gum alone were eroded faster and dissolved completely within 5-7 hr, while tablet containing HPMC remain intact and provided slow release up to 11-12 hr. It was evident from the study that the formulation F10 containing HPMC K15M and xanthan gum (1:1) exhibited maximum bioadhesive strength of 31.59±0.05 gm and in vitro drug release was found to be 91.85 % at the end of 12 hr with non-fickian diffusion mechanism. The stability studies of optimized batch showed that there was no change in bioadhesive strength and in-vitro release when stored at different temperature condition for 60 days. It was concluded that formulation F10 shows the better bioadhesive strength and drug release

Adapting federated cyberinfrastructure for shared data collection facilities in structural biology

It has been difficult, historically, to manage and maintain early-stage experimental data collected by structural biologists in synchrotron facilities. This work describes a prototype system that adapts existing federated cyberinfrastructure technology and techniques to manage collected data at synchrotrons and to facilitate the efficient and secure transfer of data to the owner’s home institution

New Signatures of Bio-Molecular Complexity in the Hypervelocity Impact Ejecta of Icy Moon Analogues

Impact delivery of prebiotic compounds to the early Earth from an impacting comet is considered to be one of the possible ways by which prebiotic molecules arrived on the Earth. Given the ubiquity of impact features observed on all planetary bodies, bolide impacts may be a common source of organics on other planetary bodies both in our own and other solar systems. Biomolecules such as amino acids have been detected on comets and are known to be synthesized due to impact-induced shock processing. Here we report the results of a set of hypervelocity impact experiments where we shocked icy mixtures of amino acids mimicking the icy surface of planetary bodies with high-speed projectiles using a two-stage light gas gun and analyzed the ejecta material after impact. Electron microscopic observations of the ejecta have shown the presence of macroscale structures with long polypeptide chains revealed from LCMS analysis. These results suggest a pathway in which impact on cometary ices containing building blocks of life can lead to the synthesis of material architectures that could have played a role in the emergence of life on the Earth and which may be applied to other planetary bodies as well. View Full-Tex

Numerical investigation of hybrid blend design target bullets

In the past few decades, researchers are involved in the studies of high-energy penetrator geometry and also the materials used for causing brutal damages on enemy targets. The highly focused area in this field is the shape of the nose and penetration angle of the penetrator. Hybrid blend design target bullets is one among the best aerodynamic design as it is having two different shapes within the nose. The design of these bullets plays an influential role in terms of aerodynamic characteristics and its dynamic performance capability on hitting the targets. Objective of this research is to perform a comparative analysis of 3 different geometrically varied shapes of these bullets by numerical simulation using CFD, based on its performance characteristics such as aerodynamic co-efficients, shock wave existence, Turbulent dissipation rate and normal drag force on the bullet surface