The Effect of Active Pharmaceutical Ingredients on Aerosol Electrostatic Charges from Pressurized Metered Dose Inhalers

The final publication is available at Springer via: http://dx.doi.org/10.1007/s11095-015-1674-6.Purpose. This study investigated the effect of different active pharmaceutical ingredients (API) on aerosol electrostatic charges and aerosol performances for pressurized metered dose inhalers (pMDIs), using both insulating and conducting actuators. Methods. Five solution-based pMDIs containing different API ingredients including: beclomethasone dipropionate (BDP), budesonide (BUD), flunisolide (FS), salbutamol base (SB) and ipratropium bromide (IPBr) were prepared using pressure filling technique. Actuator blocks made from nylon, polytetrafluoroethylene (PTFE) and aluminium were manufactured with 0.3 mm nominal orifice diameter and cone nozzle shape. Aerosol electrostatics for each pMDI formulation and actuator were evaluated using the electrical low-pressure impactor (ELPI) and drug depositions were analysed using high performance liquid chromatography (HPLC). Results. All three actuator materials showed the same net charge trend across the five active drug ingredients, with BDP, BUD and FS showing positive net charges for both nylon and PTFE actuators, respectively. While SB and IPBr had significantly negative net charges across the three different actuators, which correlates to the ionic functional groups present on the drug molecule structures. Conclusions. The API present in a pMDI has a dominant effect on the electrostatic properties of the formulation, overcoming the charge effect arising from the actuator materials. Results have shown that the electrostatic charges for a solution-based pMDI could be related to the interactions of the chemical ingredients and change in the work function for the overall formulation

Polarized ATR-FTIR spectroscopy of the membrane-embedded domains of the particulate methane monooxygenase.

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Polymeric Piezoresistive Microcantilevers With Reduced Electrical Variability

The observed electrical variability has limited the usage of the carbon black (CB)-SU8 (an epoxy polymer of di-glycidyl ether of bisphenol A) nanocomposite as a piezoresistive element in the microelectromechanical systems-based sensor applications. We report here a simple modification to the CB-SU8 nanocomposite preparation, which improves the dispersion of the CB particles in the SU8 polymer matrix creating a CB-SU8 photopatternable nanocomposite with a stable conductive network. The modified CB-SU8 nanocomposite was used as the piezoresistive element to fabricate microcantilever devices for strain sensing applications. Improved stability of these microcantilever devices is reflected from their electrical characterization. The electromechanical characterization of these microcantilevers demonstrated their piezoresistive behavior

Zinc oxide nanorods functionalized paper for protein preconcentration in biodiagnostics

Distinguishing a specific biomarker from a biofluid sample containing a large variety of proteins often requires the selective preconcentration of that particular biomarker to a detectable level for analysis. Low-cost, paper-based device is an emerging opportunity in diagnostics. In the present study, we report a novel Zinc oxide nanorods functionalized paper platform for the preconcentration of Myoglobin, a cardiac biomarker. Zinc oxide nanorods were grown on a Whatman filter paper no. 1 via the standard hydrothermal route. The growth of Zinc oxide nanorods on paper was confirmed by a combination of techniques consisting of X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS,) scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDX) analysis. The Zinc oxide nanorods modified Whatman filter paper (ZnO-NRs/WFP) was further tested for use as a protein preconcentrator. Paper-based ELISA was performed for determination of pre-concentration of cardiac marker protein Myoglobin using the new ZnO-NRs/WFP platform. The ZnO-NRs/WFP could efficiently capture the biomarker even from a very dilute solution (Myoglobin < 50 nM). Our ELISA results show a threefold enhancement in protein capture with ZnO-NRs/WFP compared to unmodified Whatman filter paper, allowing accurate protein analysis and showing the diagnostic concept

Kinetics, spectral and redox behaviour of OH adducts of methylxanthines: a radiation chemical study

The reactions of OH, O- and SO4- with mono- (MX), di- (DMX) and tri- (TMX) methylxanthines were investigated by pulse radiolysis. The second order rate constants for the OH reaction range from 8.5 × 109 dm3 mol-1 s-1 for 1,3,7-TMX to 2.4 × 109 dm3 mol-1 s-1 for 1-MX, the order being 1,3,7-TMX &gt; 1,3-DMX ≈ 3,7-DMX ≈ 7-MX &gt; 3-MX &gt; 1-MX. The second order rate constants (k ≈ 3.2-4.5 × 109 dm3 mol-1 s-1) for the SO4- reaction are comparable to those obtained in the ?OH reaction which are considerably reduced in the case of O- reaction (k = 0.33-1 × 109 dm3 mol-1 s-1). The transient absorption spectra of the OH adducts of methylxanthines (X-4OH and X-8OH) have exhibited maxima at 320-330 nm and a broad peak around 490 nm whereas the latter peak was not observed in the spectra obtained in the O- and SO4- reactions. The rates of decay of absorption around 500 nm due to the dehydration of the X-4OH? adducts are in the range 1.5-4 × 104 s-1. In contrast to the behaviour observed with 1,3,7-TMX, the X-8OH adducts of mono- and dimethylxanthines undergo ring opening with k = (4-11) × 104 s-1. The addition of O2 (N2O:O2 (4:1 v/v)) to the X-4OH adduct of methylxanthines (k = 1 × 109 dm3 mol-1 s-1) is much more effective than its dehydration. While O2 addition predominates over the ring opening in 1-MX, 3-MX and 1,3-DMX, the X-8OH adducts of 7-MX and 3,7-DMX were found to be relatively unreactive

Detection of heart-type fatty acid-binding protein (h-FABP) using piezoresistive polymer microcantilevers functionalized by a dry method

Piezoresistive microcantilever-based sensor platform is being used for the last two decades due to their low cost, rapid response and label-free detection system. In this work, we are reporting a microfabricated piezoresistive SU-8/carbon black (polymer cantilever)-based sensor platform for the detection of a clinically important early-stage cardiac marker, i.e., fatty acid-binding protein. It is a most preferred cardiac marker for the diagnosis of acute myocardial infarction. The embodiment of the sensor is a SU-8 microcantilever chip with an integrated nanoparticle composite (carbon black) as a piezoresistor for on-chip electrical transduction. Prior to improving the sensing and susceptibility towards the specific target biomolecule (i.e., h-FABP), the fabricated SU-8 polymer cantilevers were subjected to tailored functionalization. This includes the use of an in-house dry method of hot wire chemical vapour deposition technique to graft amine groups onto the SU-8 surface. The surface-modified microcantilevers were further integrated with a polydimethylsiloxane liquid flow cell and connected externally with an electrical read-out system. Immobilization of the antibody corresponding to the marker protein on the microcantilever surface and subsequent recording of the signal generated upon the antibody-antigen interaction were carried out inside the liquid flow cell. Using our optimized immobilization protocol with this experimental set-up, we were successfully able to detect h-FABP concentration as low as 100 ng/ml