Determination of cephalosporins in solid binary mixtures by polarized IR- and Raman spectroscopy.

Quantitative IR- and Raman spectroscopic determinations of four cephalosporin antibiotics in six solid binary mixtures have been conducted. This is a new approach for spectroscopic determination of these antibiotics, since the corresponding quantitative analysis in solution only has been reported so far. The correlation coefficient r2 was found to be in the confidence intervals within 99.32-99.88% and 99.90-95.54% for the systems under study by using the absorption ratios of the characteristic bands at 800 cm(-1) and 721 cm(-1) present in the IR- and Raman spectra of the antibiotic compounds cephalexin, cephalotin, cephaloglycin and cephamandole, respectively. Solid-state linear dichroic infrared (IR-LD) spectral analysis of the solid mixtures was carried out in order to obtain experimental IR-spectroscopic assignment of the compounds studied. Independent high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis was performed for the validation of the vibrational spectroscopic data. The application of this instrumental analytical tool for the analysis of 10 tablets of the commercial products Cefamandole and Cefalotin (Actavis) was also studied.

Safe use of selected cephalosporins in penicillin-allergic patients: a meta-analysis.

BACKGROUND: Recent analysis of clinical data and a clearer understanding of the role of chemical structure in the development of cross-reactivity indicate that the increased risk of an allergic reaction to a cephalosporin in penicillin-allergic patients is smaller than previously postulated. METHOD: Medline and EMBASE databases were searched with the keywords: cephalosporin, penicillin, allergy, and cross-sensitivity for the years 1960 through 2005. Among 219 articles retrieved, 9 served as source material for this evidence-based meta-analysis. RESULTS: A significant increase in allergic reactions to cephalothin (odds ratio [OR] = 2.5; 95% confidence interval [CI] = 1.1 to 5.5), cephaloridine (OR = 8.7; CI = 5.9 to 12.8), and cephalexin (OR = 5.8; CI = 3.6 to 9.2), and all first generation cephalosporins plus cefamandole (OR = 4.8; CI = 3.7 to 6.2) were observed in penicillin allergic patients; no increase was observed with second generation cephalosporins (OR = 1.1; CI, 0.6 to 2.1) or third generation cephalosporins (OR = 0.5; CI = 0.2 to 1.1). Clinical challenges, skin testing, and monoclonal antibody studies point to the paramount importance of similarities in side chain structure to predict cross-allergy between cephalosporins and penicillins. CONCLUSION: First-generation cephalosporins have cross-allergy with penicillins, but cross-allergy is negligible with second- and third-generation cephalosporins. Particular emphasis should be placed on the role of chemical structure in determining the risk of cross-reactivity between specific agents.

DFT and TD-DFT theoretical studies on photo-induced electron transfer process on [Cefamandole].C60 nano-complex.

The C60 fullerene displays a considerable electronegativity. It has a unique photophysical and electrochemical behavior that can be used as a suitable drug carrier. In the present study, the interaction of C60 fullerene as an electron recipient with the Cefamandole antibiotic was investigated in both ground and excited states using DFT and TD-DFT methods. The study of the interaction of C60 and Cefamandole via electron localization function (ELF) and reduced density gradient (RDG) revealed that the complex formation is of van der Waals type. The data from natural bonding orbitals (NBO) analysis also confirmed the interaction type. The study of absorption and emission spectrum via CAM-B3LYP in the TD-SCF state showed that the emission peak of C60 fullerene in the 591.73nm after the complex formation results in the extinction of this emission spectrum due to charge transfer (CT) from chelator to fluorophore. The photoinduced electron transfer (PET) process was investigated using the electron hole theory.

Stability and compatibility studies of cephamandole nafate with PVC infusion bags.

A rapid isocratic technique was developed for the analysis of cephamandole nafate and cephamandole in parenteral solutions using high-performance liquid chromatography (HPLC) with UV detection and C18 column. The availability and compatibility of drugs from solutions infused via plastic infusion bags through plastic administration sets have been examined. No significant drugs loss was observed during simulated infusions (n = 4) for 1 h using PVC infusion bags and administration sets. No significant difference was found between infusion solutions (5% glucose or 0.9% NaCl). The stability of drugs was also studied in solution in PVC bags after storage at room temperature and at 4 degrees C without protection from light. The results show the stability of cephamandole nafate during 24 h at room temperature and 7 days storage at 4 degrees C to be satisfactory, irrespective of the infusion solution (5% glucose or 0.9% NaCl). However, an almost immediate and total transformation of cephamandole nafate to cephamandole in 5% glucose has been observed, whereas in 0.9% NaCl both forms were found in similar proportions.

Polyurethanes loaded with antibiotics: influence of polymer-antibiotic interactions on in vitro activity against Staphylococcus epidermidis.

Acidic or basic polyurethanes were loaded with antibiotics to develop materials to prevent medical device-related infections. A correlation between polymer-antibiotic interactions and amount of drug absorbed by polymers and released over time was found. Since the employed antibiotics, i.e. amoxicillin, cefamandole nafate, rifampin and vancomycin, possessed at least an acidic group in their structural formula, the introduction of basic tertiary amines in the polyurethane side-chain resulted in an increased polymer ability to adsorb antibiotics. However, a stronger ionic interaction between this polymer and the antibiotics caused a release of lower amount of drug over time. Antibiotics released from polymers inhibited Staphylococcus epidermidis growth on agar. Antibiotic-loaded polyurethanes kept in water for increasing times were still able to show inhibition zones of bacterial growth. The antibacterial activity lasted up to 3 hours for amoxicillin, 24 hours for vancomycin, 8 days for cefamandole nafate and 8 months for rifampin.

Kinetics of cefamandole nafate degradation in solid phase.

The influence of temperature and relative humidity (RH) on the stability of cefamandole (CM) nafate sodium in the solid phase was investigated. Changes in the concentration of cefemandole nafate sodium were recorded using HPLC with UV detection. The method was validated for the following parameters: selectivity, linearity, precision, limit of detection and sensitivity. It showed good linearity (r=0.9996) in the range 0.4 x 10(-4)-5.6 x 10(-4) g ml(-1) using a LiChrospher RP-18 column and as mobile phase acetonitryle-triethylamine (10% v/v, adjusted to pH 2.5 with phosphoric acid (84%) and diluted with water) (35:65). The degradation of CM occurring at 0% RH of the ambient air and at air humidity RH>50% is a first-order reaction relative to substrate concentration. The first-order rate constants (k) were determined for CM degradation in dry air at 373, 383, 388 and 393 K, at air humidity RH=76.4% at 323, 333, 343 and 353 K, and at 353 K at air humidity RH>50%. The kinetic and thermodynamic parameters of the decomposition were calculated.

Antibiotic delivery polyurethanes containing albumin and polyallylamine nanoparticles.

Nano-structured polymers delivering an antibiotic for the prevention of medical device-related infections were developed. Systems consisted of bovine serum albumin or polyallylamine nanoparticles alone or entrapped in a polyurethane and then loaded with cefamandole nafate, chosen as a drug model. Results showed that nanoparticles alone were able to adsorb high antibiotic amounts due to their high surface/volume ratio. However, they released cefamandole in an uncontrolled fashion, leading to a rapid loss of antibacterial activity. Improvements in the release control were obtained when CEF loaded and non-loaded nanoparticles were entrapped in a carboxylated polyurethane. For these systems the drug delivery was at least of 50% with respect to nanoparticles alone with a prolonged antimicrobial activity up to 9 days.

Estimation of the two sample preparation techniques for infrared spectroscopic identification of Cefamandole nafate in solid state.

The European Pharmacopoeia (Ph.Eur.) monograph for Cefamandole Nafate (CFN) and the revised monograph prescribe the identification of the antibiotic in solid state by infrared (IR) absorption spectrophotometry using potassium bromide (KBr) disc technique. But, this technique may cause unwanted solid-solid transformations in the crystalline structure of the beta-lactam antibiotic CFN. The latter is a drug with proven polymorphism/pseudopolymorphism. In this context we have examined the suitability of the two techniques (KBr disc and Nujol mull) for IR spectral analyses to identify the antibiotic CFN in solid state. The results of our examinations show that KBr disc technique alters the crystalline state of CFN during the preparation of its KBr disc samples by the tribomechanical treatments (grinding and compression pressure). On the contrary, the Nujol mull technique does not cause such transformations and it is estimated as a better, more suitable technique to be employed for identification of CFN. For a greater precision, in solving the possible difficulties due to the KBr disc technique a second record of IR spectra is necessary to be provided by the Nujol mull technique with use of an internal standard (the stretching vibration of vC = 0 of the condensed beta-lactam cycle).

Synergistic activity of dispersin B and cefamandole nafate in inhibition of staphylococcal biofilm growth on polyurethanes.

Antibiotic therapies to eradicate medical device-associated infections often fail because of the ability of sessile bacteria, encased in their exopolysaccharide matrix, to be more drug resistant than planktonic organisms. In the last two decades, several strategies to prevent microbial adhesion and biofilm formation on the surfaces of medical devices, based mainly on the use of antiadhesive, antiseptic, and antibiotic coatings on polymer surfaces, have been developed. More recent alternative approaches are based on molecules able to interfere with quorum-sensing phenomena or to dissolve biofilms. Interestingly, a newly purified beta-N-acetylglucosaminidase, dispersin B, produced by the gram-negative periodontal pathogen Actinobacillus actinomycetemcomitans, is able to dissolve mature biofilms produced by Staphylococcus epidermidis as well as some other bacterial species. Therefore, in this study, we developed new polymeric matrices able to bind dispersin B either alone or in combination with an antibiotic molecule, cefamandole nafate (CEF). We showed that our functionalized polyurethanes could adsorb a significant amount of dispersin B, which was able to exert its hydrolytic activity against the exopolysaccharide matrix produced by staphylococcal strains. When microbial biofilms were exposed to both dispersin B and CEF, a synergistic action became evident, thus characterizing these polymer-dispersin B-antibiotic systems as promising, highly effective tools for preventing bacterial colonization of medical devices.

Coupling between chemical reactivity and structural relaxation in pharmaceutical glasses.

PURPOSE: To test the hypothesis that the molecular motions associated with chemical degradation in glassy amorphous systems are governed by the molecular motions associated with structural relaxation. The extent to which a chemical process is linked to the motions associated with structural relaxation will depend on the nature of the chemical process and molecular motion requirements (e.g., translation of a complete molecule, rotational diffusion of a chemical functional group). In this study the chemical degradation and molecular mobility were measured in model systems to assess the degree of coupling between chemical reactivity and structural relaxation. The model systems included pure amorphous cephalosporin drugs, and amorphous molecular mixtures containing a chemically labile drug and an additive expected to moderate molecular mobility. METHODS: Amorphous drugs and mixtures with additives were prepared by lyophilization from aqueous solution. The physical properties of the model systems were characterized using optical microscopy and differential scanning calorimetry. The chemical degradation of the drugs alone and in mixtures with additives was measured using high-performance liquid chromatography (HPLC). Molecular mobility was measured using isothermal microcalorimetry to measure enthalpy changes associated with structural relaxation below T (g). RESULTS: A weak correlation between the rates of degradation and structural relaxation times in pure amorphous cephalosporins suggests that reactivity in these systems is coupled to molecular motions in the glassy state. However, when sucrose was added to one of the cephalosporin drugs stability improved even though this addition reduced T (g) and the relaxation time constant, tau(D)(beta), suggesting that there was no correlation between reactivity and structural relaxation in the cephalosporin mixtures. In contrast, the rate of ethacrynate sodium dimer formation in mixtures was more strongly coupled to the relaxation time constant, tau(D)(beta). CONCLUSIONS: These studies suggest that the extent to which chemical degradation is coupled to structural relaxation in glasses motions is determined by how closely the motions of the rate controlling step in chemical degradation are associated with structural relaxation. Moderate coupling between the rate of dimer formation for ethacrynate sodium in mixtures with sucrose, trehalose and PVP and structural relaxation constants suggests that chemical changes that require more significant molecular motion, and includes at least some translational diffusion, are more strongly coupled to the molecular motions associated with structural relaxation. The observation that sucrose stabilizes cefoxitin sodium even though it lowers T (g) and reduces the relaxation time constant, tau(D)(beta) is perhaps a result of the importance of other kinds of molecular motions in determining the chemical reactivity in glasses.