P. Venkata Ramana

Synthesis, characterization, and evaluation of differently sulfonated resins as novel carriers for drug delivery

The 2-methacryloxyacetophenone (MAP) was prepared and subjected to suspension polymerization with divinylbenzene (DVB). The differently sulfonated MAP–DVB cross-linked copolymer cationic exchange resins were prepared by sulfonation with a fixed volume of concentrated sulfuric acid in an oil bath at 70 oC. Several characteristics of the prepared resins were evaluated, i.e. Fourier transform infrared spectra, the ion-exchange capacity, and microscopic morphology. The resin characteristics were altered with degree of sulfonation, providing that differently sulfonated resins could be prepared. The behavior of Fexofenadine hydrochloride loading and in vitro release in the USP stimulated gastric and intestinal fluids of the obtained resins were evaluated. The drug loaded in the resin increased with increasing degree of sulfonic group and hence the drug binding site in resin employed. The drug release was lower from the resins with higher degree of sulfonic group due to the increase in the diffusive path depth. The drug release was a little lower in stimulated gastric fluid (SGF) than stimulated intestinal fluids. The basic group, ionized to a little greater extent in SGF and preferred binding with the resin rather than releasing. Hence, the differently sulfonated resins could be utilized as novel carriers for drug delivery.

Oxidative Amidation of Benzyl Alcohols with Amino Acid Esters Mediated by N-hydroxysuccinimide/phenyliodine Diacetate

ABSTRACT A simple protocol involving metal-free oxidative amidation of benzyl alcohols with amino acid esters has been presented. The amidation proceeds in a radical pathway unlike in conventional metal-mediated extrusion of dihydrogen. The method is advantageous in terms of metal-free conditions, nonexpensive commercial starting substrates. Also various substituents in the starting materials are tolerated and sterically hindered amino acid side chains could provide good yields of amide products. GRAPHICAL ABSTRACT

Controlled Drug Release Studies of Atenolol Using Differently Sulfonated Acryloxyacetophenone and Methyl Methacrylate Copolymer Resins as Drug Carriers

Abstract2-Acryloxyacetophenone (AAP) was prepared and subjected to suspension polymerization with methyl methacrylate (MMA) using azobisisobutyronitrile (AIBN) as free radical initiator. The differently sulfonated AAP-MMA cross-linked copolymer cationic exchange resins were prepared by sulfonation with concentrated sulphuric acid at 70 °C. Several characteristics of the prepared resins were evaluated, i.e. FTIR, the ion-exchange capacity (IEC), thermo gravimetric analysis (TGA), particle size distribution and microscopic morphology. The resin characteristics were altered with degree of sulfonation, providing that differently sulfonated resins could be prepared. The behavior of atenolol (ATL) loading and in vitro release in the USP stimulated gastric and intestinal fluids of the obtained resins were evaluated. The drug loaded in the resin increased with increasing degree of sulfonation and hence the drug binding site in resin employed. The drug release was lower from the resins with higher content of sulfonic group due to the increase in the diffusive path depth. The drug release was a little lower in stimulated gastric fluid (SGF) than in stimulated intestinal fluids (SIF). The basic groups, ionized to a little greater extent in SGF and preferred binding with the resin rather than releasing. Hence, the differently sulfonated resins could be utilized as novel carriers for drug delivery.

Synthesis, characterization and evaluation of antibacterial activity of (E)-N′-(substituted benzylidene)-2-(2-fluorobenzyl)-5-ethyl-2H-1,2,3-triazole-4-carbohydrazides

Triazoles and their derivatives are important precursors in the pharmacological field due to their broad diversity of medicinal and biological deed. In this article, the exploration is to put an effort to produce some novel biologically active triazole 4-carbohydrazide derivatives. The structures of the newly synthesized compounds were characterized and confirmed by spectral data and were screened for anti-bacterial activity. Compounds 5(d-i), 5l and 5m were observed to possess potent anti-microbial activity.

Synthesis, Characterization and Thermal Studies of Polymer–Metal Complexes Derived from Poly(4-Methacryloxybenzaldehyde)-Divinylbenzene Benzoyl Hydrazone Resins

4-Methacryloxybenzaldehyde was prepared and subjected to suspension polymerization with divinylbenzene as a cross-linking agent. The resulting network polymer was ligated with benzoyl hydrazone. The functional polymer was treated with transition metal ions (Cu(II), Ni(II)). The polymer–metal complexes were characterized by elemental analysis, IR, 1H-NMR, solid state 13C cross-polarization magic-angle spinning (CP/MAS) NMR, electron paramagnetic resonance (EPR), thermogravimetric and scanning electron microscopy (SEM) studies.

Peptide Bond Formation via N α -Protected Diacyldiselenides

A simple, straightforward, for the peptide bond formation employing corresponding carboxylic acids and amines derived from amino acids via Nα-protected diacyldiselenide is delineated. The key step of the synthesis is the in situ generation of Nα-protected diacyldiselenide using NaBH2Se3 as selenating reagent, followed by trapping with an amino acid ester leading to the peptide. The formation of Nα-protected diacyldiselenide was confirmed through TLC and HRMS analysis using crude sample. The reaction is clean and all the products were obtained in moderate to good yields, including for sterically hindered amino acids. The protocol is free from racemisation, compatible with Fmoc, Cbz and Boc groups.Graphical Abstract

Development of Novel RP-HPLC Method for Separation and Estimation of Critical Geometric Isomer and Other Related Impurities of Tafluprost Drug Substance and Identification of Major Degradation Compounds by Using LC–MS

A novel, simple, sensitive and stability-indicating reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the quantitative determination of the geometric isomer (Trans) and other related substances in the active pharmaceutical ingredient (API) of Tafluprost (TFL), with their determination by an assay. A chromatographic separation of TFL and its impurities was achieved with a C18 analytical column, using gradient elution with mobile phase A consisting of a mixture of water, methanol and orthophosphoric acid (900:100:1, v/v) and mobile phase B consisting of a mixture of acetonitrile and water (900:100, v/v). The instrumental settings included a flow rate of 1.0 mL/min for related substances and 1.2 mL/min for the assay, a column temperature of 50°C and a detector wavelength of 210 nm, using a photodiode array detector. TFL was exposed to thermal, photolytic, hydrolytic and oxidative stress conditions and the stressed samples were analyzed by the proposed method. Peak homogeneity data of TFL were obtained by using a photodiode array detector in the stressed sample chromatograms, which demonstrated the specificity of the method for estimation in the presence of degradants. The developed method was validated for parameters such as precision, accuracy, linearity, limit of detection, limit of quantification, ruggedness and robustness as per ICH guidelines.

A Rapid Novel HPLC Method for Estimation of Eight Related Compounds in Azilsartan Kamedoxomil and Identification of Degradation Compounds by Using LC-MS

A novel, rapid, specific and stability-indicating reverse-phase high-performance liquid chromatography method was developed for the quantitative determination of related compounds, obtained from two different synthetic routes and degradation products of Azilsartan kamedoxomil (AZL). The method was developed by using a YMC-Pack pro C18 (150 × 4.6 mm, 3 µm) column with a mobile phase containing a gradient mobile phase combination. The eluted compounds were measured at wavelength 220 nm. The developed method run time was 25 min, within which AZL and its eight impurities were well separated with minimum 3.0 resolution. The drug substance was subjected to stress conditions of hydrolysis (acid, base and water), oxidation, photolysis, sunlight, 75% relative humidity and thermal degradation as per International Conference on Harmonization (ICH) prescribed stress conditions to ascertain the stability-indicating power of the method. Significant degradation was observed during acid, base, peroxide, water hydrolysis and 75% relative humidity studies. The mass balance of AZL was close to 100% in all the stress condition. The developed method was validated as per the ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness.

Synthesis of new 5-((2-(substituted phenoxymethyl)-1H-benzo[d]imidazol-1-yl)methyl)-1,3,4-oxadiazole-2-thiol: A novel class of potential antibacterial and antifungal agents

Novel 1,3,4-Oxadiazoles bearing benzimidazole nucleus were designed, synthesized using 2-(2-(substituted phenoxymethyl)-1H-benzo[d]imidazol-1-yl)acetohydrazide and carbon disulfide. These newly synthesized benzimidazolyl oxadiazoles along with benzimidazolyl acetates and benzimidazolyl acetohydrazides were screened for their antibacterial activity against two kinds of strains using the agar disk diffusion method and antifungal activity against Aspergillus niger and Ustilago maydis. The results showed that some of the compounds exhibited moderate activity against both the strains in antibacterial activity and majority of compounds are not active in antifungal activity. The structure-activity relationships were briefly discussed. The studies indicated that compounds of Benzimidazolyl acetohydrazide were the most potent inhibitors compared to the other compounds under investigation.