A brief review on critical analytical aspects for quantification of ambroxol in biological samples.

Ambroxol (AMB) is a member of the expectorant class, widely used as a secreolytic agent in patients to break up secretions. AMB is rapidly and effectively distributed from blood to tissue. The lungs have the highest concentration of AMB; accumulation of AMB in human lung tissue was detected at concentrations 15- to 20-fold greater than those reported in the circulation. Because of its wide range of actions and therapeutic applications may be worth looking into, particularly for respiratory symptoms, antioxidant, anti-inflammatory, influenza, and rhinovirus infections. Though several analytical methodologies have been established and confirmed for the AMB analysis in matrices of pharmaceutical and biological origins, novel sustainable, and economical methods are still to be choice of protocol to increase its sensitivity, reliability, and repeatability. Therefore, the present review offers an overview of critical analytical aspects regarding the HPLC, LC-MS/MS, HPTLC, capillary electrophoresis, spectrophotometry, and electrochemical methods for quantifying AMB in pharmaceutical and biological samples. Furthermore, this review will thoroughly discuss the physicochemical properties, stability, extraction conditions, instrumentation, and operational parameters of the targeted analyte. As a result, for the first time, this review complies with vital background information and an up-to-date interpretation of research undertaken by anticipated methodologies examined and implemented for the pharmaceutical analysis AMB.

HPLC-PDA identification and resolution of rufinamide forced degradation impurities: A congregated chemometric expedite optimization coupled with factorials and desirability.

Rufinamide is used presently to treat Lenaux-Gastaut syndrome. A full factorial design and desirability approach was investigated for the optimization of hydrolytic stress via response surface curves (RSCs). The degradation impurities were identified and resolved using reversed-phase high-performance liquid chromatography (RP-HPLC) on the Qualisil® BDS C8 column. Acetonitrile-water (29:71, v/v) was optimized for the mobile phase and used at a flow rate of 1.0 ml/min with detection at a wavelength of 230 nm. Rufinamide showed appreciable susceptibility to hydrolysis under acidic and alkaline stress, and substantial degradation in the neutral condition. It degraded much less under oxidative stress. Exposure towards thermal and photolytic stress conditions indicated appreciable stability. The developed method was subjected to validation as per the recommendations of the International Conference on Harmonization. The proposed method showed no influence from the excipients and the degradation products. As well as good precision and accuracy in determination, the method showed a linear response between 2 and 12 µg ml-1 . The method was extended for determination in a human plasma sample, which resulted in excellent recovery without interference from matrix effects. The combined use of desirability and design for the optimization of acidic and alkaline hydrolytic stress led to simple and rapid analysis.

Terahertz Spectroscopy: Encoding the Discovery, Instrumentation, and Applications toward Pharmaceutical Prospectives.

Terahertz (THz) spectroscopy is an emerging field for quality control of pharmaceuticals, which uses T-waves for detection. T-waves fall in between infrared and microwave radiations while possessing some of the characteristics of both. THz spectroscopy reveals its existence in between 0.1 and 10 THz. These radiations have the ability to penetrate a broad range of non-conductive materials and it is nonionizing. The first article stating the use of THz radiations was found in late 1960 for the generation of the astronomical images. This review essentially creates attention toward different forms and instrumentation of THz spectroscopy along with the updates for timely and upbeat pharmaceutical applications. The most frequently used technique is THz-TDS which has profoundly privileged applicability for the pharmaceuticals. The existing literature of THz spectroscopy further created albeit interest to explore the applications for future implementation in concern with the pharmaceuticals. The review critically outlines here all the pharmaceutical applications of THz spectroscopy including protein analyses, crystallinity studies, evaluating tablet films and coats, medicinal aging variations, and detection of illicit drugs, along with the advantages over traditional techniques. The other side of THz spectroscopy stating limitations is also studied and taken into the note to present here. This review is a genuine attempt to quote and crucially assess the possible as well as anticipated prospectives for the pharmaceuticals. The present article will further promote the awareness, opportunities, and scientific exploration of this exciting technology as THz spectroscopy.

Pharmaceutical Analytical Profile for Novel SGL-2 Inhibitor: Dapagliflozin.

Dapagliflozin (DPG) is a novel drug from class of sodium glucose co-transporter 2 (SGL-2) inhibitors which has been evolved as profound treatment option for the type-2diabetes mellitus (T2DM). Considering the severity of the disease the drug is of crucial significance for the therapy and associated research. As a pharmaceutical dosage form DPG has immense importance as an individual drug and with other antidiabetic drugs as combinations. The drugs existing in combination with DPG are Metformin (MET) and Saxagliptin (SXG). The existence of the Dapagliflozin in combinations further created more interest in reviewing its pharmaceutical, analytical and bio-analytical profile. Such estimations are always in need of precise pharmacological and physicochemical information; hence authors have presented it beforehand. Authors hereby wish to present an essential update pertaining to emergence of gliflozins and DPG. The article further presents a simultaneous and comparative assessment of the analytical investigations published in literature for pharmaceutical estimation to assist future analysis. The thorough literature searches revealed fifty three research papers in total till date. A comprehensive presentation of typical; hyphenated and unique methods used for analysis are outlined effectively. The percentile utilization of analytical approaches since appearance of first publication in 2010 is investigated to report trend in determination. The present review explores the pharmaceutical estimation of DPG to scientifically potentiate analytical research and therapeutic future of DPG as a novel SGL-2 Inhibitor antidiabetic.

Hydrotropic Solubilization in Pharmaceutical Analysis: Origin, Evolution, Cumulative Trend and Precise Applications.

The hydrotropy though existing as precisely used scientific approach assisting solubilization for all. It took 66 long years to use the concept in drug analysis since its inception in 1916 and first use for facilitation of drug solubility toward better pharmaceutical analysis in 1982. Considering the unending importance in pharmaceutical sciences and thereby in analysis, it's a necessity to comprehensively outlook the origin, evolution, cumulative trend and precise applications in pharmaceutical analysis. Achieved hereby with chronological and comparative assessment of the studies published pertaining to solubility enhancement of poorly soluble drugs with use of hydrotropic agents alone or in combination for assisting pharmaceutical analysis. The thorough literature searches resulted into 77 references over a span of about 38 years. This comprehensive review critically evaluates existing literature; to our surprise we found Ibuprofen sodium, Lignocaine, Niacinamide and Metformin HCl as atypical hydrotropic agents. We also compared herein mono and mixed approaches which indicated prevalence of mono - hydrotropy over mixed. The possible mechanisms behind solubilization are presented for an additional insight. An essential effort has been made to state arbitrary classification to assist in future applications. The obvious purpose of this study was to collectively evaluate the crucial role of hydrotropic agents in pharmaceutical analyses for better drug delivery. This comprehensive review covers all details since inception to the updates till date which will definitely act as appropriate guideline for pharmaceutical analyst's in need of hydrotropy to assist pharmaceutical analysis for therapies today and tomorrow.

Pharmaceutical analysis combined with in-silico therapeutic and toxicological profiling on zileuton and its impurities to assist in modern drug discovery.

The obligatory testing of drug molecules and their impurities to protect users against toxic compounds seems to provide interesting opportunities for new drug discovery. Impurities, which proved to be non-toxic, may be explored for their own therapeutic potential and thus be a part of future drug discovery. The essential role of pharmaceutical analysis can thus be extended to achieve this purpose. The present study examined these objectives by characterizing the major degradation products of zileuton (ZLT), a 5-lipoxygenase (5-LOX) inhibitor being prevalently used to treat asthma. The drug sample was exposed to forced degradation and found susceptible to hydrolysis and oxidative stress. The obtained Forced Degradation Products (FDP's) were resolved using an earlier developed and validated Ultra-High-Pressure Liquid Chromatography Photo-Diode-Array (UHPLC-PDA) protocol. ZLT, along with acid-and alkali-stressed samples, were subjected to Liquid-chromatography Mass-spectrometry Quadrupole Time-of-flight (LC/MS-QTOF) studies. Major degradation products were isolated using Preparative TLC and characterized using Q-TOF and/or Proton nuclear magnetic resonance (1HNMR) studies. The information obtained was assembled for structural conformation. Toxicity Prediction using Komputer Assisted Technology (TOPKAT) toxicity analyses indicated some FDP's as non-toxic when compared to ZLT. Hence, these non-toxic impurities may have bio-affinity and can be explored to interact with other therapeutic targets, to assist in drug discovery. The drug molecule and the characterized FDP's were subjected to 3-Dimensional Extra Precision (3D-XP)-molecular docking to explore changes in bio-affinity for the 5-LOX enzyme (PDB Id: 3V99). One FDP was found to have a higher binding affinity than the drug itself, indicating it may be a suitable antiasthmatic. The possibility of being active at other sites cannot be neglected and this is evaluated to a reasonable extent by Prediction of Activity Spectra for Substances (PASS). Besides being antiasthmatic, some FDP's were predicted antineoplastic, antiallergic and inhibitors of Complement Factor-D.

Novel 3-substituted-1-aryl-5-phenyl-6-anilinopyrazolo[3,4-d]pyrimidin-4-ones: docking, synthesis and pharmacological evaluation as a potential anti-inflammatory agents.

Novel 3-substituted-1-aryl-5-phenyl-6-anilino-pyrazolo[3,4-d]pyrimidin-4-ones of pharmacological significance were synthesized by the reaction of ethyl-(5-amino-3-methylthio-1-aryl-5-phenyl-2H-pyrazole)-4-carboxylates 3a-c with S-methyl diphenyl thiourea independently to produce 1-aryl-3-thiomethyl-5-phenyl-pyrazolo[3,4-d]pyrimidines 4a-c in DMF with catalytic amount of K(2)CO(3), which on further treatment with different aromatic amines independently under same reaction conditions generated for compounds 5a-l. The compounds were screened for the anti-inflammatory activity and evaluated for ulcerogenic potential. The compounds 5i exhibited superior anti-inflammatory activity in comparison with diclofenac sodium and comparable activity with celecoxib at a dose of 25mg/kg. The other compounds 4c, 5c, 5f and 5l were found as active with inhibition of edema in the range of 35-39 after 3 h of administration of test compounds. The ulcerogenic potential of active compounds was observed to be quite lesser as compared to standard. COX-2 docking score of the active compound 5i was found to be better than standard celecoxib.