Formulation and development of ophthalmic in situ gel for the treatment ocular inflammation and infection using application of quality by design concept

Context: The conventional liquid ophthalmic delivery systems exhibit short pre-corneal residence time and the relative impermeability to the cornea which leads to poor ocular bioavailability.

Objective: The aim of this study was to apply quality by design (QbD) for development of dexamethasone sodium phosphate (DSP) and tobramycin sulfate (TS)-loaded thermoresponsive ophthalmic in situ gel containing Poloxamer 407 and hydroxyl propyl methyl cellulose (HPMC) K4M for prolonging the pre-corneal residence time, ocular bioavability and decreases the frequency of administration of dosage form. The material attributes and the critical quality attributes (CQA) of the in situ gel were identified. Central composite design (CCD) was adopted to optimize the formulation.

Materials and methods: The ophthalmic in situ forming gels were prepared by cold method. Materials attributes were the amount of Poloxamer 407 and HPMC and CQA identified were Gel strength, mucoadhesive index, gelation temperature and % of drug release of both drug.

Results and discussion: Optimized batch (F*) containing 16.75% poloxamer 407 and 0.54% HPMC K4M were exhibited all results in acceptable limits. Compared with the marketed formulation, optimized in situ gel showed delayed T_max, improved C_max and AUC in rabbit aqueous humor, suggesting the sustained drug release and better corneal penetration and absorption.

Conclusion: According to the study, it could be concluded that DSP and TS would be successfully formulated as in situ gelling mucoadhesive system for the treatment of steroid responsive eye infections with the properties of sustained drug release, prolonged ocular retention and improved corneal penetration.     

High efficiency ultra-thin sputtered CdTe solar cells

Large scale manufacturing of CdTe PV modules at the GW/yr level may be constrained due to the limited availability of the relatively rare (Te) element and the volume of potentially hazardous (Cd) material being used in the typically 3–8 μm thick CdTe absorber layer. However, we find that it is possible to reduce the CdTe layer thickness without much compromise in efficiency. The CdS/CdTe solar cells were fabricated using magnetron sputtering with ultra-thin CdTe layers in the range of 0.5–1.28 μm. The ultra-thin films and cells were characterized using X-ray diffraction (XRD), optical transmission, scanning electron microscopy (SEM), current–voltage and quantum efficiency measurements. These results were compared with those of standard 2.3 μm thick CdTe sputtered cells. Different post-deposition processing parameters were required for cells with ultra-thin and standard CdTe thicknesses to achieve high efficiency. Ultra-thin CdTe cells showed crystallographic texture and CdTe_1−xS_x alloy formation after CdCl₂ treatment very similar to standard CdTe cells. Optimization of the post-deposition CdCl₂ treatment and back-contact processing yielded cells of 11.2% efficiency with 0.7 μm CdTe compared to 13.0% obtained with standard 2.3 μm CdTe cells.     

60 GHz indoor WLANs: insights into performance and power consumption

This paper presents a feasibility study of 60 GHz indoor WLANs. We evaluate 60 GHz performance in a typical academic office building under the primary assumption that 60 GHz WLAN APs and clients will be equipped with relatively wide-beam antennas to cope with client mobility. In contrast to previous works which measured performance at a single layer using custom, non-standard compliant hardware, we investigate performance across multiple layers using primarily 802.11ad-compliant wide-beam COTS devices. Our study shows that the large number of reflective surfaces in typical indoor WLAN environments combined with wider beams makes performance highly unpredictable and invalidates several assumptions that hold true in static, narrow-beam, Line-Of-Sight scenarios. Additionally, we present the first measurements, to our best knowledge, of power consumption of an 802.11ad NIC and examine the impact of a number of factors on power consumption.     

Quantification of Pentafluorobenzyl Oxime Derivatives of Long Chain Aldehydes by GC–MS Analysis

Negative ion mass spectrometric techniques, for compounds having good ionization properties, such as pentafluorobenzyl derivatives, are believed to be more sensitive than positive ion methods. Preparation of PFB oximes of fatty aldehydes from crude lipid extracts is problematic due to the release of free aldehydes from plasmalogens during derivatization. Accordingly, in these studies plasmalogens were removed by silicic acid column chromatography prior to pentafluorobenzyl derivatization. This simple purification step to remove plasmalogens is shown to facilitate the quantification of long-chain aldehydes by analysis of their pentafluorobenzyl oxime derivatives utilizing gas chromatography–mass spectrometry in the negative ion chemical ionization mode. The limit of detection for long chain fatty aldehydes using this method is 0.5 pmol and it is linear over two orders of magnitude. Silicic acid column chromatography followed by electrospray ionization mass spectrometry demonstrated that plasmalogens were removed (the detection limit for this analyses was ≤0.3 pmol). Furthermore, we have exploited the utility and sensitivity of this method to identify increases in hexadecanal and octadecanal in 3-amino-1,2,4-triazole treated human neutrophils. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Anisotropic photoresponse investigation of chemical vapor transport (CVT) grown quaternary Cu2ZnSnS4 single crystals

The single crystals of quaternary transition metal chalcogenide Cu₂ZnSnS₄ (CZTS) are grown by a closed system chemical vapor transport technique. The high purity individual elemental precursors are employed in the growth of the crystals. These crystals are found to be single-phase by X-ray diffraction and Raman analysis. The near stoichiometry of the grown crystals is confirmed by spectroscopy analysis of the photoelectron generated by X-rays and analysis of the energy of the dispersive X-rays generated by electrons. The surface study by scanning electron microscopy showed the growth to happen by sheet spread mean and the electron diffraction showed fringe width match with (112) plane spacing. The study of the CZTS/Ag-paste/Cu-wire system for incident white light and three wavelengths of laser lights in two configuration modes of top-contact (II to the plane) and bottom-top-contact (⊥ to the plane) showed anisotropic behavior. The incident white light illumination intensity of 120 mW/cm² showed utmost photoresponse. The top-contact mode configuration showed maximum responsivity and detectivity of 0.72 mA/W and 0.33 × 10⁹ Jones, respectively, while bottom-top-contact showed 0.18 mA/W and 0.13 × 10⁹ Jones, respectively. The anisotropic photoresponse by the CZTS crystals insinuates the potential for future applications.

     

Chemopreventive agent resveratrol, a natural product derived from grapes, triggers CD95 signaling-dependent apoptosis in human tumor cells

Resveratrol, a constituent of grapes and other food products, has been shown to prevent carcinogenesis in murine models. We report here that resveratrol induces apoptotic cell death in HL60 human leukemia cell line. Resveratrol-treated tumor cells exhibit a dose-dependent increase in externalization of inner membrane phosphatidylserine and in cellular content of subdiploid DNA, indicating loss of membrane phospholipid asymmetry and DNA fragmentation. Resveratrol-induced cell death is mediated by intracellular caspases as observed by the dose-dependent increase in proteolytic cleavage of caspase substrate poly (ADP-ribose) polymerase (PARP) and the ability of caspase inhibitors to block resveratrol cytotoxicity. We also show that resveratrol treatment enhances CD95L expression on HL60 cells, as well as T47D breast carcinoma cells, and that resveratrol-mediated cell death is specifically CD95-signaling dependent. On the contrary, resveratrol treatment of normal human peripheral blood lymphocytes (PBLs) does not affect cell survival for up to 72 hours, which correlates with the absence of a significant change in either CD95 or CD95L expression on treated PBLs. These data show specific involvement of the CD95-CD95L system in the anti-cancer activity of resveratrol and highlight the chemotherapeutic potential of this natural product, in addition to its recently reported chemopreventive activity.     

Photodynamic Therapy in Non-Gastrointestinal Thoracic Malignancies

Photodynamic therapy has a role in the management of early and late thoracic malignancies. It can be used to facilitate minimally-invasive treatment of early endobronchial tumours and also to palliate obstructive and bleeding effects of advanced endobronchial tumours. Photodynamic therapy has been used as a means of downsizing tumours to allow for resection, as well as reducing the extent of resection necessary. It has also been used successfully for minimally-invasive management of local recurrences, which is especially valuable for patients who are not eligible for radiation therapy. Photodynamic therapy has also shown promising results in mesothelioma and pleural-based metastatic disease. As new generation photosensitizers are being developed and tested and methodological issues continue to be addressed, the role of photodynamic therapy in thoracic malignancies continues to evolve.     

Formulation development and characterization of cellulose acetate nitrate based propellants for improved insensitive munitions properties

Cellulose acetate nitrate （CAN） was used as an insensitive energetic binder to improve the insensitive munitions （IM） properties of gun propellants to replace the M1 propellant used in 105 mm artillery charges. CAN contains the energetic nitro groups found in nitrocellulose （NC）, but also acetyl functionalities, which lowered the polymer＇s sensitivity to heat and shock, and therefore improved its IM properties relative to NC. The formulation, development and small-scale characterization testing of several CAN-based propellants were done. The formulations, using insensitive energetic solid fillers and high-nitrogen modifiers in place of nitramine were completed. The small scale characterization testing, such as closed bomb testing, small scale sensitivity, thermal stability, and chemical compatibility were done. The mechanical response of the pro- pellants under high-rate uni-axial compression at, hot, cold, and ambient temperatures were also completed. Critical diameter testing, hot fragment conductive ignition （HFCI） tests were done to evaluate the propellants＇ responses to thermal and shock stimuli. Utilizing the propellant chemical composition, theoretical predictions of erosivity were completed. All the small scale test results were utilized to down-select the promising CAN based formulations for large scale demonstration testing such as the ballistic performance and fragment impact testing in the 105 mm M67 artillery charge configurations. The test results completed in the small and large scale testing are discussed.     

Statistical evaluation of influence of xanthan gum and guar gum blends on dipyridamole release from floating matrix tablets

The present investigation explored the use of xanthan gum and guar gum for development of floating drug delivery system of dipyridamole using factorial design approach. The content of polymer blends (X(1)) and ratio of xanthan gum to guar gum (X(2)) were selected as independent variables. The diffusion exponent (n), release rate constant (k), percentage drug release at 1 hr (Q(1)) and 6 hr (Q(6)) were selected as dependent variables. Tablets of all batches had desired buoyancy characteristics. Multiple regression analysis with two way ANOVA revealed that both the factors had statistically significant influence on the response studied (p<0.05). Results of Tukey test showed the relative contribution of each level of different factors for the response studied. It was concluded that the ratio of xanthan to gaur gum had equal or dominant role as controlling factor on kinetics of drug release compared to content of polymer blends.     

Analysis on DC and RF/Analog Performance in Multifin-FinFET for Wide Variation in Work Function of Metal Gate

Silicon - It is well established that increase in number of fins improves the RF/Analog performances of FinFET. In this paper, the effect of work function (ɸM) of metal gate on transfer...