Preparation and characterization of cyclodextrin complexes of doxycycline hyclate for improved photostability in aqueous solution

Doxycycline hyclate is Biopharmaceutical Classification System, class I drug (high solubility and high permeability), but it is associated with poor photostability. It is in the class of tetracycline antibiotic, which is used to treat various infections, but its bioavailability is compromised due to its sensitivity to light and aqueous instability. In this paper, the influence of inclusion complexation with different cyclodextrins, i.e., αCD, γCD, HPβCD and RMβCD, on the photostability of doxycycline hyclate in aqueous media was investigated. Host–guest inclusion complexes were prepared by freeze- drying method. The prepared complexes were characterized for drug content, SEM, XRPD, in vitro permeation studies and photostability studies. XRPD showed diffused peaks for most of the complexes, while SEM showed irregularly shaped particles. The formulation D20 (Drug: γCD in 1:20 molar ratio) showed the highest % drug content (83.72?±?1.2%), and the formulations D1 (Drug: αCD in 1: 2 molar ratio) showed the lowest % drug content among all the CD complexes. It was found that the photodegradation of the drug was reduced significantly upon complexation. For Drug: CD complexes, the photostability of the aqueous solution of drug/CD complexes was found to be in the order of γCD?>?RMβCD?>?HPβCD?>?αCD with maximum photostability shown by Drug: γCD (1:20 molar ratio) complex. The obtained results suggested that cyclodextrin complexation can be used as an alternative approach for increasing the photostability of doxycycline hyclate.

     

Green synthesis and anticancer activity of tetrahydrodipyrazolo[3,4-b:4′,3′-e]pyridines catalyzed by phospho sulfonic acid

Biologically portent/significant tetrahydrodipyrazolo[3,4-b:4′,3′-e]pyridines are synthesized by an efficient green synthesis of various aldehydes with 3-methyl-1H-pyrazol-5(4H)-one in ammonium acetate using phospho sulfonic acid as a solid catalyst under microwave-assisted interaction under solvent-free conditions at 70°C. This methodology is easy to handle and get good to excellent yields. Later the potential in vitro antiproliferation of the titled compounds is evaluated. Among all the titled compounds, 4s and 4t showed the most potent anticancer potentiality on the used cancer cell lines of SK-BR-3 and HeLa (IC₅₀ = 10.70 ± 0.27 and 12.58 ± 0.38, and 19.38 ± 0.32 and 21.55 ± 0.41 μg/mL for SK-BR-3 cells lines and HeLa cells lines, respectively), which were comparable to the positive control.     

New Measurements of Internal Conversion Coefficients in $${}^{{111}}$$ Cd

Physics of Atomic Nuclei - The 7.5-day beta decay of $${}^{111}$$ Ag is studied with a 60 cc HPGe gamma spectrometer system and a high transmission Mini-Orange magnetic spectrometer. Precise gamma...     

Significance of Satellite DNA Revealed by Conservation of a Widespread Repeat DNA Sequence Among Angiosperms

The analysis of plant genome structure and evolution requires comprehensive characterization of repetitive sequences that make up the majority of plant nuclear DNA. In the present study, we analyzed the nature of pCtKpnI-I and pCtKpnI-II tandem repeated sequences, reported earlier in Carthamus tinctorius. Interestingly, homolog of pCtKpnI-I repeat sequence was also found to be present in widely divergent families of angiosperms. pCtKpnI-I showed high sequence similarity but low copy number among various taxa of different families of angiosperms analyzed. In comparison, pCtKpnI-II was specific to the genus Carthamus and was not present in any other taxa analyzed. The molecular structure of pCtKpnI-I was analyzed in various unrelated taxa of angiosperms to decipher the evolutionary conserved nature of the sequence and its possible functional role.     

High sensitivity liquid chromatography tandem mass spectrometric methods for the analysis of dioctyl sulfosuccinate in different stages of an oil spill response monitoring effort

After the incident on the Deepwater Horizon platform, around 1.8 million gallons of dispersants were used in the field as part of the response cleanup efforts. This study describes an online solid phase extraction–liquid chromatography (LC)–tandem mass spectrometry (MS/MS) method and a direct-injection LC-MS/MS method for the analysis of dioctyl sulfosuccinate (DOSS; a component in Corexit® EC9500A) in seawater at trace levels, with method detection limits (MDLs) of 7.0 and 440 ng/L and run times of 7 and 17 min, respectively. Stability and preservation studies demonstrated that samples at 4.7 μg/L could be preserved for up to 150 days without loss of analyte when stored with 33 % acetonitrile in glass containers. Data acquisition was performed by heated electrospray ionization (ESI) MS/MS operating in negative mode. Methods were validated in terms of percent recovery in fortified blank and matrix samples and to evaluate carryover. A simple modification of the direct-injection method allowed quantitation of 2-butoxyethanol, a dispersant component specific to the Corexit® EC9527A formulation. This method was used to simultaneously quantify DOSS and 2-butoxyethanol in two Corexit® formulations and extracts from an MC-252 source oil standard. MDLs in crude oil were 0.723 and 4.46 mg/kg, respectively, with recoveries of (92?±?9)% for DOSS and (104?±?8)% for 2-butoxyethanol. Detection of both indicators was achieved in a single chromatographic run by ESI-MS/MS operating sequentially in positive and negative mode. Corexit® EC9500A and Corexit® EC9527A were found to contain (21?±?2)% and (22?±?5)% w/w DOSS and 0 and (37?±?2)% w/w 2-butoxyethanol, respectively.     

Novel Metal- and Mineral-Acid–Free Synthesis of Organic Ammonium Tribromides and Application of Ethylenephenanthrolium Bistribromide for Bromination of Active Methylene Group of 1,3-Diketones and β-Ketoesters

A novel procedure for the preparation of organic ammonium tribromides (OATBs) is described from their corresponding bromides. Quaternary ammonium bromides (QABs) and a N,N′-heterocyclic dibromide are efficiently oxidized to their corresponding monotribromides and bistribromide by m-chloroperbenzoic acid (MCPBA) in the presence of 2 and 4 equiv of KBr, respectively. The reactions are carried out in an aqueous medium without the use of any mineral acid or metal catalyst/promoters. A variety of tribromides are synthesized in very good yields including a hitherto unknown reagent, 1,10-(ethane-1, 2-diyl)phenanthrolinediium bistribromide (EPDBT). EPDBT is investigated as brominating agent and found to be highly effective for selective bromination of active methylene groups of a variety of 1,3-diketones and β-ketoesters.     

Potential of Thermo and Alkali Stable Xylanases from Thielaviopsis basicola (MTCC-1467) in Biobleaching of Wood Kraft Pulp

Thermo- and alkali-stable xylanases produced from Thielaviopsis basicola (MTCC-1467) on low-cost carbon source like rice straw were evaluated for their potential application in biobleaching of wood kraft pulp. Enzyme treatment at retention time of 240?min with 20?IU/gm of dried pulp resulted in ~85.2?% of reduction in kappa number. When compared to control, 110.8, 93, and 72.2?% of enhancement in brightness (percent International Organization of Standardization), whiteness, and fluorescence, respectively, were observed for enzyme-treated pulp. Spectroscopic analysis showed significant release of chromophoric compounds from enzyme-treated pulp. Furthermore, scanning electron microscope studies of unbleached and enzyme bleached pulp revealed the effectiveness of enzymatic treatment. The enzyme-treated pulp subjected to later stages of chemical bleaching resulted in 16?% decrease in chlorine consumption along with considerable reduction in chemical oxygen demand percentage (14.5?%) level of effluent. Various pulp properties like fiber length, fiber width, burst strength, burst index, tear strength, tear index, tensile strength, and breaking length were also significantly improved after enzyme treatment when compared to control.     

Synthesis, characterization and biological evaluation of mononuclear Co(II), Ni(II), Cu(II) and Pd(II) complexes with new N2O2 Schiff base ligands

New tetradentate N(2)O(2) donor Schiff bases and their mononuclear Co(II), Ni(II), Cu(II), and Pd(II) complexes were synthesized and characterized extensively by IR, (1)H-, (13)C-NMR, mass, ESR, conductivity measurements, elemental and thermal analysis. Specifically the magnetic and electronic spectral measurements demonstrate the octahedral structures of cobalt(II), nickel(II) complexes and square planar geometries of copper(II), palladium(II) complexes. All the ligands and complexes were screened for their in vitro antibacterial activity against two gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus) and two gram-negative bacteria (Escherichia coli, Klebsiella pneumonia). In this study, Pd(II) complexes exhibited potent antibacterial activity against B. subtilis, S. aureus whereas other metal complexes also exerted good activity towards all tested strains even than standard drugs streptomycin and ampicillin.     

Phosphite mediated asymmetric N to C migration for the synthesis of chiral heterocycles from primary amines

A phosphite mediated stereoretentive C–H alkylation of N-alkylpyridinium salts derived from chiral primary amines was achieved. The reaction proceeds through the activation of the N-alkylpyridinium salt substrate with a nucleophilic phosphite catalyst, followed by a base mediated [1,2] aza-Wittig rearrangement and subsequent catalyst dissociation for an overall N to C-2 alkyl migration. The scope and degree of stereoretention were studied, and both experimental and theoretical investigations were performed to support an unprecedented aza-Wittig rearrangement–rearomatization sequence. A catalytic enantioselective version starting with racemic starting material and chiral phosphite catalyst was also established following our understanding of the stereoretentive process. This method provides efficient access to tertiary and quaternary stereogenic centers in pyridine systems, which are prevalent in drugs, bioactive natural products, chiral ligands, and catalysts.

N-Alkylpyridinium salt of chiral amines undergoes phosphite mediated stereoretentive migrations to generate chiral alkylpyridines. The role of phosphite on reactivity and stereoselectivity were examined to achieve a catalytic asymmetric version.     

A novel microextraction by packed sorbent–gas chromatography procedure for the simultaneous analysis of antiepileptic drugs in human plasma and urine

A simple, accurate, and sensitive microextraction by packed sorbent–gas chromatography‐mass spectrometry method has been developed for the simultaneous quantification of four antiepileptic drugs; oxcarbazepine, carbamazepine, phenytoin, and alprazolam in human plasma and urine as a tool for drug monitoring. Caffeine was used as internal standards for the electron ionization mode. An original pretreatment procedure on biological samples, based on microextraction in packed syringe using C₁₈ as packing material gave high extraction yields (69.92–99.38%), satisfactory precision (RSD < 4.7%) and good selectivity. Linearity was found in the 0.1–500 ng/mL range for these drugs with limits of detection (LODs) between 0.0018 and 0.0036 ng/mL. Therefore, the method has been found to be suitable for the therapeutic drug monitoring of patients treated with oxcarbazepine, carbamazepine, phenytoin, and alprazolam. After validation, the method was successfully applied to some plasma samples from patients undergoing therapy with one or more of these drugs. A comparison of the detection limit with similar methods indicates high sensitivity of the present method over the earlier reported methods. The present method is applied for the analysis of these drugs in the real urine and plasma samples of the epileptic patients.