Detailed solvent, structural, quantum chemical study and antimicrobial activity of isatin Schiff base.

The ratios of E/Z isomers of sixteen synthesized 1,3-dihydro-3-(substituted phenylimino)-2H-indol-2-one were studied using experimental and theoretical methodology. Linear solvation energy relationships (LSER) rationalized solvent influence of the solvent-solute interactions on the UV-Vis absorption maxima shifts (νmax) of both geometrical isomers using the Kamlet-Taft equation. Linear free energy relationships (LFER) in the form of single substituent parameter equation (SSP) was used to analyze substituent effect on pKa, NMR chemical shifts and νmax values. Electron charge density was obtained by the use of Quantum Theory of Atoms in Molecules, i.e. Bader's analysis. The substituent and solvent effect on intramolecular charge transfer (ICT) were interpreted with the aid of time-dependent density functional (TD-DFT) method. Additionally, the results of TD-DFT calculations quantified the efficiency of ICT from the calculated charge-transfer distance (DCT) and amount of transferred charge (QCT). The antimicrobial activity was evaluated using broth microdilution method. 3D QSAR modeling was used to demonstrate the influence of substituents effect as well as molecule geometry on antimicrobial activity.

Top-Down and Bottom-Up Approaches in 3D Printing Technologies for Drug Delivery Challenges.

3-Dimensional printing (3DP) constitutes a raft of technologies, based on different physical mechanisms, that generate a 3-dimensional physical object from a digital model. Because of its rapid fabrication and precise geometry, 3DP has gained a prominent focus in biomedical and nanobiomaterials research. Despite advancements in targeted, controlled, and pulsatile drug delivery, the achievement of site-specific and disease-responsive drug release and stringent control over in vivo biodistribution, are still some of the important, challenging areas for pharmaceutical research and development and existing drug delivery techniques. Microelectronic industries are capable of generating nano-/microdrug delivery devices at high throughputs with a highly precise control over design. Successful miniaturizations of micro-pumps with multireservoir architectures for delivery of pharmaceuticals developed by micro-electromechanical systems technology were more acceptable than implantable devices. Inkjet printing technologies, which dispense a precise amount of polymer ink solutions, find applications in controlled drug delivery. Bioelectronic products have revolutionized drug delivery technologies. Designing nanoparticles by nanoimprint lithography showed a controlled drug release pattern, biodistribution, and in vivo transport. This review highlights the "top-down" and "bottom-up" approaches of the most promising 3DP technologies and their broader applications in biomedical and therapeutic drug delivery, with critical assessment of its merits, demerits, and intellectual property rights challenges.

In vitro-in vivo studies of the quantitative effect of calcium, multivitamins and milk on single dose ciprofloxacin bioavailability.

Ciprofloxacin, commonly used in India as an anti-microbial for prolonged use in chronic and non-specific indications, may affect the bioavailability of the drug. The drug prescribed is commonly taken with multivitamins, calcium and milk. A simple and reliable analytical methodology obtaining a correlation with in vivo urinary excretion studies using UV and HPLC and in vitro dissolution studies (IVIVC) has shown a significant increase in elimination rate of ciprofloxacin co-administered with multivitamins, calcium and milk. Appreciable IVIVC results proved that dissolution studies could serve as an alternative to in vivo bioavailability and also support bio-waivers.

An Experimental Design Approach for Impurity Profiling of Valacyclovir-Related Products by RP-HPLC.

Impurity profiling has become an important phase of pharmaceutical research where both spectroscopic and chromatographic methods find applications. The analytical methodology needs to be very sensitive, specific, and precise which will separate and determine the impurity of interest at the 0.1% level. Current research reports a validated RP-HPLC method to detect and separate valacyclovir-related impurities (Imp-E and Imp-G) using the Box-Behnken design approach of response surface methodology. A gradient mobile phase (buffer: acetonitrile as mobile phase A and acetonitrile: methanol as mobile phase B) was used. Linearity was found in the concentration range of 50-150 µg/mL. The mean recovery of impurities was 99.9% and 103.2%, respectively. The %RSD for the peak areas of Imp-E and Imp-G were 0.9 and 0.1, respectively. No blank interferences at the retention times of the impurities suggest the specificity of the method. The LOD values were 0.0024 µg/mL for Imp-E and 0.04 µg/mL for Imp-G and the LOQ values were obtained as 0.0082 µg/mL and 0.136 µg/mL, respectively, for the impurities. The S/N ratios in both cases were within the specification limits. Proper peak shapes and satisfactory resolution with good retention times suggested the suitability of the method for impurity profiling of valacyclovir-related drug substances.