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Lenalidomide (LND) is an analogue of thalidomide that is second generation immunomodulatory drugs (IMiDs). LND contains asymmetric carbon atom and exist R and S enantiomer. S (-) form of enantiomer are considered to be more potent and biologically active in tumor cell. It is available in racemic form for clinical use. The study aims to develop and validate enantiomer separation of LND in human plasma. The chromatographic enantiomeric separation was achieved on a Daicel-CSP, Chiralpack IA 4.6 × 250 mm_5 μm. The mobile phase was constituted in combination of methanol:glacial acetic acid at a concentration of 499.50 ml: 50 μl. UV wavelength detection was 220 nm. The RSD% for all validation parameters was found to be within the acceptable limit. The chiral chromatographic (chiral stationary phase-high-performance liquid chromatography [CSP-HPLC]) method developed and validated for the quantitative estimation of LND enantiomers S (-) and R (+) in human plasma sample is accurate, precise, robust, stable and selective.

A simple, rapid, sensitive and specific gas chromatography–tandem mass spectrometry (GC–MS/MS) method was developed for quantitation of salbutamol in human urine using salbutamol-d3 as the internal standard. The processing of urines samples includes deconjugation with enzymatic hydrolysis, solid phase extraction procedure utilizing XAD2 column and liquid–liquid extraction accompanied by the derivatization by means of MSTFA/IODO–TMS/DTE mixture. The GC column was a HP Ultra-1 (17 m × 0.22 mm × 0.11 μm) used to separate the peak of interest. The data for GC–MS/MS were acquired and processed utilizing GC Labs Solution and Insight GCMS Software. The detection of spectra was performed on TQ 8050. This method included a chromatographic run of 13.67 min and the linearity was found over the concentration range of 250–2000 ng/mL with a regression coefficient (r2) of 0.99. The coefficient of variation for intra and interday assay precision was between 1.85 and 2.85% and the accuracy was between 95.50 and 107.04% for low quality control (QC), medium QC and high QC. The recovery was adequate to reliable detect the analyte at or below the level recommended by the World Anti-Doping Agency i.e., threshold 1000 ng/mL. The limit of detection and limit of quantification were found to be 10 and 100 ng/mL, respectively. The expanded measurement uncertainty (Uexp%) was found to be 8.28%.

Nanomedicine combination therapy, a strategy to delivery multiple drugs via a single nanosystem has opened new avenues to treat cancer and prevent side effects and overcome chemoresistance. The present work utilizes a chemotherapeutic agent topotecan hydrochlorideand a natural chemosensitizer (thymoquinone, TQ) incorporated into poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) to target tumor. The objective of the present work is to develop a reversed phase HPLC method for simultaneous estimation of TQ along with the pH dependent lactone and carboxylate forms of topotecan and validate its applicability. Chromatographic separation was obtained on Agilent 1200 Infinity series C18 analytical column using gradient elution with acetonitrile and 1% triethylamine acetate (TEAA) buffer (pH 5.5) as mobile phase and a flow rate of 0.8 mL/min. Analytical detection was done at 253 nm. Validation was performed as per ICH guidelines and characterization and stability of the optimized nanoparticles were evaluated. The retention time of 5.93, 8.73, and 19.76 min was obtained for lactone, carboxylate and TQ, respectively. Linearity response was established in the range of 5‒45 µg/mL. The limits of detection and quantification were found to be 15 and 50 ng/mL for lactone, 18 and 59 ng/mL for carboxylate, and 5 and 18 ng/mL for TQ, respectively. The method was validated in terms of robustness, precision, accuracy, specificity and percent loading, entrapment efficiency, and in vitro drug release. The stability of the nanoparticles was determined using the above validated method. The method was successfully validated and applied for routine analyses indicating its use as a suitable analytical tool to determine efficiency of the proposed therapy.

The aim of the present work was to optimize processing parameters for the preparation of Ficus religiosa L. extract loaded solid lipid nanoparticles (SLN) using central composite design. Optimization was carried out using four factors such as homogenization speed, homogenization time, sonication time and sonication intensity and three responses studied were particle size, polydispersity index (PDI) and zeta potential to obtain a SLN batch with lesser particle size, optimum PDI and higher zeta potential. Further, optimized batch was characterized for entrapment efficiency, surface morphology, in-vitro release and kinetics, fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder Xray diffraction (PXRD) and stability over 6 months. From the results, it was observed that increase in homogenization speed and time decreased particle size and PDI with increase in zeta potential value. Increase in sonication time up to 5 min decreased particle size and further increase had no effect on particle size. Sonication intensity had very little effect. DSC and PXRD showed reduced crystallinity of extract in SLN form. Also, the optimized batch had stability over 6 months. Further, SLN significantly reduced diabetes induced higher levels of blood glucose and increased diabetes induced lower level of plasma insulin.

The aim of this work was to evaluate the quantitative characterization and pharmaceutical compatibility study of teneligliptin (TNG) with the commonly used excipients for solid dosage form employing thermogravimetric analysis, differential scanning calorimetry, liquid chromatography–mass spectrometer, powder X-ray diffraction, isothermal stress testing, optical microscopy and Fourier transform infrared spectroscopy as a supporting technique to contribute to the interpretation of results. The selected excipients were magnesium stearate (MS), sodium starch glycolate (SSG), croscarmellose sodium (CCS), pregelatinized starch (PS) and microcrystalline cellulose (MCC). On the basis of the DSC results, some interactions were found with TNG–CCS, TNG–MCC, TNG–MS, TNG–SSG and TNG–PS. However, during IST studies less than 3% change in TNG content was observed in all stressed binary mixtures except TNG–CCS, TNG–SSG (

In spite of wide applications of herbal drugs as phytochemicals or extracts, their application is limited because of their poor bioavailability. The aim of the present work was to enhance the poor bioavailability of lupeol present in Ficus religiosa L. extract through solid lipid nanoparticles (SLN). Ficus religiosa L. extract loaded SLN were prepared and administered orally to male Wistar rats for bioavailability studies. Developed SLN were characterized for particle size, PDI, zeta potential, entrapment efficiency, in vitro drug release and stability studies. Further, interaction studies were carried out. Bioavailability studies were performed for Ficus religiosa L. extract in suspension form and SLN form. AUC of lupeol was increased by 9.2 - folds in rats treated with SLN compared to suspension. Also, C max of lupeol was increased by 3.9 - folds in rats treated with SLN compared to suspension. t 1/2 of lupeol was found to be 7.3 ± 1.0 h in suspension and 15.3 ± 1.3 h in SLN. SLN enhanced AUC and C max and prolonged t 1/2 of lupeol in Ficus religiosa L. extract which in turn may lead to dose reduction, prolonged duration of action and also enhanced therapeutic efficacy.

Roflumilast (RFL), a newly approved and highly selective phosphodiesterase 4 inhibitor for the treatment of severe chronic obstructive pulmonary disease, associated with chronic bronchitis and a history of numerous exacerbations. The main objective of this work was to evaluate the simultaneous (TG/DSC) thermoanalytical characterization and compatibility of roflumilast with the widely used excipients for solid dosage form employing differential scanning calorimetry (DSC), thermogravimetric analysis (TG), optical microscopy, isothermal stress testing (IST) by HPLC and liquid chromatography–mass spectrometer techniques with Fourier transform infrared spectroscopy (FT-IR) as a complimentary technique to contribute in the interpretation of results. The selected excipients were pregelatinized starch (PS), magnesium stearate, croscarmellose sodium (CCS), microcrystalline cellulose (MCC) and sodium starch glycolate (SSG). The DSC curve showed a sharp endothermic melting peak at 160.43 °C for roflumilast. On the basis of the DSC results, some interactions were found with RFL–CCS, RFL–MCC, RFL–SSG and RFL–PS. However, during IST studies less than 2% change in roflumilast content was observed in all stressed physical mixtures except RFL–SSG (

One-pot condensation of 4-hydroxy coumarins, aldehydes and urea/thiourea to build C–C and C–N bonds is described. Fused pyrimidines have been synthesized under mild reaction conditions using L-proline. The protocol has been performed rapidly and efficiently in water under metal free conditions. Heterocyclic derivatives have been synthesized using the present methodology and avoid the use of hazardous solvents over conventional organic solvents. A proposed mechanism could be established for three component reactions. The present study reveals the first case in which L-proline has been explored as a homogeneous catalyst in the synthesis of fused pyrimidines in water under microwave irradiation. This synthesis involves simple workup and acceptable efficiency. The most notable feature of this protocol is the ability of the catalyst to influence asymmetric induction in the reaction.