Films based on chitosan polyelectrolyte complexes for skin drug delivery: Development and characterization

Novel chitosan based polyelectrolyte complexes (PEC) were developed and optimized in order to obtain films possessing the optimal functional properties (flexibility, resistance, water vapour transmission rate and bioadhesion) to be applied on skin. The development was based on the combination of chitosan and two polyacrylic acid (PAA) polymers with different crosslinkers and crosslinking densities. The interaction between the polymers was maximized controlling the pH, and by forming the films at a pH value close to the pK_a of the respective components as identified by potentiometric and turbidimetric titrations. The action of glycerol, PEG200, Hydrovance and trehalose upon the functional properties of the films was also evaluated. Glycerol was found to improve the film properties in terms of flexibility, resistance and water vapour transmission rate (WVTR) with a maximum effect at 30%. The application of a pressure sensitive adhesive (PSA) significantly improved bioadhesion with a negligible influence in the resistance and flexibility of the films.The optimized film, including adhesive, has shown very good properties for application in the skin and represents a very promising formulation for further incorporation of drugs for topical and transdermal administration.     

Optical characterization and composition of abdominal wall muscle from rat

Complete optical characterization of biological tissue is desirable to develop clinical methods using optical technologies. Particularly, to develop optical clearing methods in biological tissues, it is necessary to know the composition of the tissue, the percentage of each constituent and corresponding refractive indexes. To obtain such information for rat muscle, we used a simple method to characterize tissue constituents for both content percentage and refractive index. The study consisted on measuring mass with a precision weighting scale and the refractive index with an Abbe refractometer during tissue dehydration. With the collected data, we used a theoretical model to calculate the refractive index and percentage for both interstitial fluid and solid part of the rat muscle. The results obtained are in good agreement with data published by other authors, and were considered of vital information for the optical clearing studies that we planned to perform.     

Fourier transform infrared and Raman spectra. Semi empirical AM1 and PM3; MP2/DZV and DFT/B3LYP-6-31G(d) ab initio calculations for dimethylterephthalate (DMT)

Fourier transform infrared and Raman spectra of dimethylterephthalate (DMT), as microcrystalline powder, have been investigated. The vibrational spectra were calculated using the AM1 and PM3 semi empirical procedures, and the M?ller-Plesset (MP2/DZV), and the Becke-Lee, Yang and Parr gradient-corrected correlation functional: B3LYP/6-31G(d) ab initio calculations. On this basis, and assisted with the FT-IR and Raman spectra of the terephthalic acid, an assignment of the vibrational spectra of dimethylterephthalate was proposed. In the calculations, remarkable differences concerning the assignments of the vibrational spectra were noted between the AM1 and PM3 methods. Also, the ab initio procedure shows differences in interpreting the spectra compared with the semi empiric procedures, and among themselves. Calculated geometrical parameters were compared with the experimental values of dimethylterephthalate, diethylterephthalate and terephthalic acid.     

Differentiation of aminomethyl corrole isomers by mass spectrometry

Two new isomeric aminomethyl corrole derivatives of [5,10,15-tris(pentafluorophenyl)corrolato]gallium(III) were synthesized with pyridine (py) molecules as axial ligands. When investigated by electrospray ionization mass spectrometry, in the positive and the negative ion modes, these compounds showed an unusual gas-phase behavior that could be used for their differentiation. In the positive ion mode, the differentiation was achieved through the formation of diagnostic fragment ions formed from [M-py?+?H](+) precursors, by (CH(3) )(2) NH and HF losses. An unusual addition of water to the main fragment ions provides an alternative route for isomer identification. Semi-empirical calculations were performed to elucidate the structures and stabilities of the main ionic species formed in the positive ion mode. In the negative ion mode isomer discrimination is accomplished via the fragmentation of the methoxide adduct ions [M-py?+?CH(3) O](-) through (CH(3) )(2) N(.) and HF losses.     

Differentiation of aminomethyl corrole isomers by mass spectrometry

Two new isomeric aminomethyl corrole derivatives of [5,10,15‐tris(pentafluorophenyl)corrolato]gallium(III) were synthesized with pyridine (py) molecules as axial ligands. When investigated by electrospray ionization mass spectrometry, in the positive and the negative ion modes, these compounds showed an unusual gas‐phase behavior that could be used for their differentiation. In the positive ion mode, the differentiation was achieved through the formation of diagnostic fragment ions formed from [M‐py + H]⁺ precursors, by (CH₃)₂NH and HF losses. An unusual addition of water to the main fragment ions provides an alternative route for isomer identification. Semi‐empirical calculations were performed to elucidate the structures and stabilities of the main ionic species formed in the positive ion mode. In the negative ion mode isomer discrimination is accomplished via the fragmentation of the methoxide adduct ions [M‐py + CH₃O]^‐ through (CH₃)₂ N^. and HF losses. Copyright © 2012 John Wiley & Sons, Ltd.     

Infrared spectroscopy and the characterization of terfenadine crystallized from solvents

In this paper the structural characterization of terfenadine crystallized from ethanol-water, ethanol and methanol is performed by infrared spectroscopy. The OH stretching vibration, composed of three markedly overlapped bands, is analyzed by peak fitting. The assignment of the hydrogen bonds was conducted making use of band parameters, spectroscopic data for CCl₄ solutions, and molecular dynamics calculations from dimeric systems. Terfenadine just precipitated from solvents is never in the highest crystalline state. This state is reached when the samples are heated at a temperature above 100°C. Some amorphous solid is coprecipitated with the crystalline phase, particularly in methanol. This revised version was published online in August 2006 with corrections to the Cover Date.     

Measurement of the alpha-secondary kinetic isotope effect for the reaction catalyzed by mammalian protein farnesyltransferase

Protein farnesytransferase (FTase) catalyzes the transfer of a 15-carbon prenyl group from farnesyl diphosphate (FPP) to the cysteine residue of target proteins and is a member of the newest class of zinc metalloenzymes that catalyze sulfur alkylation. Common substrates of FTase include oncogenic Ras proteins, and therefore inhibitors are under development for the treatment of various cancers. An increased understanding of the salient features of the chemical transition state of FTase may aid in the design of potent inhibitors and enhance our understanding of the mechanism of this class of zinc enzymes. To investigate the transition state of FTase we have used transient kinetics to measure the alpha-secondary 3H kinetic isotope effect at the sensitive C1 position of FPP. The isotope effect for the FTase single turnover reaction using a peptide substrate that is farnesylated rapidly is near unity, indicating that a conformational change, rather than farnesylation, is the rate-limiting step. To look at the chemical step, the kinetic isotope effect was measured as 1.154 +/- 0.006 for a peptide that is farnesylated slowly, and these data suggest that FTase proceeds via a concerted mechanism with dissociative character.     

Design of simulated moving bed and Varicol processes for preparative separations with a low number of columns

Simulated moving bed (SMB) chromatography has received significant attention in the last decade, particularly as regards the production of very valuable products, such as enantiomerically pure pharmaceutical compounds. Recent applications in the pharmaceutical industry use SMB systems containing a low total number chromatographic columns, usually four to eight. This paper deals with the modeling and simulation of SMB systems with only four, five and six columns. In particular, two modeling strategies, the equivalent true moving bed and the real SMB models, are compared for these units in terms of separation regions and system productivity. Also, the recently proposed Varicol process is analyzed and compared with the classical SMB operation, and the advantages of this new operation mode are shown for systems using a low number of columns.