Excipient characterization and particle engineering to develop directly compressed orally disintegrating tablets

ODTs have emerged as a novel oral dosage form with a potential to deliver a wide range of drug candidates to paediatric and geriatric patients. Compression of excipients offers a costeffective and translatable methodology for the manufacture of ODTs. Though, technical challenges prevail such as difficulty to achieve suitable tablet mechanical strength while ensuring rapid disintegration in the mouth, poor compressibility of preferred ODT diluent Dmannitol, and limited use for modified drug-release. The work investigates excipients’ functionality in ODTs and proposes new methodologies for enhancing material characteristics via process and particle engineering. It also aims to expand ODT applications for modified drug-release. Preformulation and formulation studies employed a plethora of techniques/tests including AFM, SEM, DSC, XRD, TGA, HSM, FTIR, hardness, disintegration time, friability, stress/strain and Heckel analysis. Tableting of D-mannitol and cellulosic excipients utilised various compression forces, material concentrations and grades. Engineered D-mannitol particles were made by spray drying mannitol with pore former NH4HCO3. Coated microparticles of model API omeprazole were prepared using water-based film forming polymers. The results of nanoscopic investigations elucidated the compression profiles of ODT excipients. Strong densification of MCC (Py is 625 MPa) occurs due to conglomeration of physicomechanical factors whereas D-mannitol fragments under pressure leading to poor compacts. Addition of cellulosic excipients (L-HPC and HPMC) and granular mannitol to powder mannitol was required to mechanically strengthen the dosage form (hardness >60 N, friability <1%) and to maintain rapid disintegration (<30 sec). Similarly, functionality was integrated into D-mannitol by fabrication of porous, yet, resilient particles which resulted in upto 150% increase in the hardness of compacts. The formulated particles provided resistance to fracture under pressure due to inherent elasticity while promoted tablet disintegration (50-77% reduction in disintegration time) due to porous nature. Additionally, coated microparticles provided an ODT-appropriate modified-release coating strategy by preventing drug (omeprazole) release.

Codon-precise, synthetic, antibody fragment libraries built using automated hexamer codon additions and validated through next generation sequencing

We have previously described ProxiMAX, a technology that enables the fabrication of precise, combinatorial gene libraries via codon-by-codon saturation mutagenesis. ProxiMAX was originally performed using manual, enzymatic transfer of codons via blunt-end ligation. Here we present Colibra™: an automated, proprietary version of ProxiMAX used specifically for antibody library generation, in which double-codon hexamers are transferred during the saturation cycling process. The reduction in process complexity, resulting library quality and an unprecedented saturation of up to 24 contiguous codons are described. Utility of the method is demonstrated via fabrication of complementarity determining regions (CDR) in antibody fragment libraries and next generation sequencing (NGS) analysis of their quality and diversity.

Practical and prospective slow light Surface Nanoscale Axial Photonics (SNAP) devices

Miniature slow light Surface Nanoscale Axial Photonics (SNAP) devices are reviewed. The fabrication precision of these devices is two orders of magnitude higher and the transmission losses are two orders of magnitude smaller than for any of the previously reported technologies for fabrication of miniature photonic circuits. In the first part of the report, a SNAP bottle resonator with a few nm high radius variation is demonstrated as the record small, slow light, and low loss 2.6 ns dispersionless delay line of 100 ps pulses. Next, a record small SNAP bottle resonator exhibiting the 20 ns/nm dispersion compensation of 100 ps pulses is demonstrated. In the second part of the report, the prospects of the SNAP technology in applications to telecommunications, optical signal processing, quantum computing, and microfluidics are discussed. © 2014 IEEE.

Nanobump microresonator

We introduce a whispering gallery-mode (WGM) nanobump microresonator (NBMR) and develop its theory. This microresonator is formed by an asymmetric nanoscale-high deformation of the translationally symmetric optical fiber surface, which is employed in fabrication of surface nanoscale axial photonics (SNAP) structures. It is shown that an NBMR causes strong localization of WGMs near a closed ray (geodesic) at the fiber surface, provided that this ray is stable. Our theory explains and describes the experimentally observed localization of WGMs by NBMRs and is useful for the design and fabrication of SNAP devices.

Liquid core fibre Bragg grating based refractive index sensor formed by femtosecond assisted chemical etching technique

We report the fabrication of a refractive index (RI) sensor based on a liquid core fibre Bragg grating (FBG). A micro-slot FBG was created in standard telecom optical fibre employing the tightly focused femtosecond laser inscription aided chemical etching. A micro-slot with dimensions of 5.74(h) × 125(w) × 1388.72(l) μm was engraved across the whole fibre and along 1mm long FBG which gives advantage of a relatively robust liquid core waveguide. The device performed the refractive index sensitivity up to about 742.72 nm/RIU. © 2011 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

Advanced FBG structures designed and fabricated for optical signal processing

We review our recent research on the design and fabrication of advanced fiber Bragg grating structures for optical signal processing. FBG based processors including optical differentiators, pulse shapers and modulation format converters are discussed. © 2015 OSA.

Ionized cluster beam deposition: Modeling, cluster size measurement and applications

Clusters are aggregations of atoms or molecules, generally intermediate in size between individual atoms and aggregates that are large enough to be called bulk matter. Clusters can also be called nanoparticles, because their size is on the order of nanometers or tens of nanometers. A new field has begun to take shape called nanostructured materials which takes advantage of these atom clusters. The ultra-small size of building blocks leads to dramatically different properties and it is anticipated that such atomically engineered materials will be able to be tailored to perform as no previous material could.^ The idea of ionized cluster beam (ICB) thin film deposition technique was first proposed by Takagi in 1972. It was based upon using a supersonic jet source to produce, ionize and accelerate beams of atomic clusters onto substrates in a vacuum environment. Conditions for formation of cluster beams suitable for thin film deposition have only recently been established following twenty years of effort. Zinc clusters over 1,000 atoms in average size have been synthesized both in our lab and that of Gspann. More recently, other methods of synthesizing clusters and nanoparticles, using different types of cluster sources, have come under development.^ In this work, we studied different aspects of nanoparticle beams. The work includes refinement of a model of the cluster formation mechanism, development of a new real-time, in situ cluster size measurement method, and study of the use of ICB in the fabrication of semiconductor devices.^ The formation process of the vaporized-metal cluster beam was simulated and investigated using classical nucleation theory and one dimensional gas flow equations. Zinc cluster sizes predicted at the nozzle exit are in good quantitative agreement with experimental results in our laboratory.^ A novel in situ real-time mass, energy and velocity measurement apparatus has been designed, built and tested. This small size time-of-flight mass spectrometer is suitable to be used in our cluster deposition systems and does not suffer from problems related to other methods of cluster size measurement like: requirement for specialized ionizing lasers, inductive electrical or electromagnetic coupling, dependency on the assumption of homogeneous nucleation, limits on the size measurement and non real-time capability. Measured ion energies using the electrostatic energy analyzer are in good accordance with values obtained from computer simulation. The velocity (v) is measured by pulsing the cluster beam and measuring the time of delay between the pulse and analyzer output current. The mass of a particle is calculated from m = (2E/v$\sp2).$ The error in the measured value of background gas mass is on the order of 28% of the mass of one N$\sb2$ molecule which is negligible for the measurement of large size clusters. This resolution in cluster size measurement is very acceptable for our purposes.^ Selective area deposition onto conducting patterns overlying insulating substrates was demonstrated using intense, fully-ionized cluster beams. Parameters influencing the selectivity are ion energy, repelling voltage, the ratio of the conductor to insulator dimension, and substrate thickness. ^

Carbon nanotube reinforced aluminum based nanocomposite fabricated by thermal spray forming

The present research concentrates on the fabrication of bulk aluminum matrix nanocomposite structures with carbon nanotube reinforcement. The objective of the work was to fabricate and characterize multi-walled carbon nanotube (MWCNT) reinforced hypereutectic Al-Si (23 wt% Si, 2 wt% Ni, 1 wt% Cu, rest Al) nanocomposite bulk structure with nanocrystalline matrix through thermal spray forming techniques viz. plasma spray forming (PSF) and high velocity oxy-fuel (HVOF) spray forming. This is the first research study, which has shown that thermal spray forming can be successfully used to synthesize carbon nanotube reinforced nanocomposites. Microstructural characterization based on quantitative microscopy, scanning and transmission electron microscopy (SEM and TEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), Raman spectroscopy and X ray photoelectron spectroscopy (XPS) confirms (i) retention and macro/sub-macro level homogenous distribution of multiwalled carbon nanotubes in the Al-Si matrix and (ii) evolution of nanostructured grains in the matrix. Formation of ultrathin β-SiC layer on MWCNT surface, due to chemical reaction of Si atoms diffusing from Al-Si alloy and C atoms from the outer walls of MWCNTs has been confirmed theoretically and experimentally. The presence of SiC layer at the interface improves the wettability and the interfacial adhesion between the MWCNT reinforcement and the Al-Si matrix. Sintering of the as-sprayed nanocomposites was carried out in an inert environment for further densification. As-sprayed PSF nanocomposite showed lower microhardness compared to HVOF, due to the higher porosity content and lower residual stress. The hardness of the nanocomposites increased with sintering time due to effective pore removal. Uniaxial tensile test on CNT-bulk nanocomposite was carried out, which is the first ever study of such nature. The tensile test results showed inconsistency in the data attributed to inhomogeneous microstructure and limitation of the test samples geometry. The elastic moduli of nanocomposites were computed using different micromechanics models and compared with experimentally measured values. The elastic moduli of nanocomposites measured by nanoindentation technique, increased gradually with sintering attributed to porosity removal. The experimentally measured values conformed better with theoretically predicted values, particularly in the case of Hashin-Shtrikman bound method.

Functionalized carbon nanotube nanoelectrodes for biomolecular recognition

The objective of this research is to develop nanoscale ultrasensitive transducers for detection of biological species at molecular level using carbon nanotubes as nanoelectrodes. Rapid detection of ultra low concentration or even single DNA molecules are essential for medical diagnosis and treatment, pharmaceutical applications, gene sequencing as well as forensic analysis. Here the use of functionalized single walled carbon nanotubes (SWNT) as nanoscale detection platform for rapid detection of single DNA molecules is demonstrated. The detection principle is based on obtaining electrical signal from a single amine terminated DNA molecule which is covalently bridged between two ends of an SWNT separated by a nanoscale gap. The synthesis, fabrication, chemical functionalization of nanoelectrodes and DNA attachment were optimized to perform reliable electrical characterization these molecules. Using this detection system fundamental study on charge transport in DNA molecule of both genomic and non genomic sequences is performed. We measured an electrical signal of about 30 pA through a hybridized DNA molecule of 80 base pair in length which encodes a portion of sequence of H5N1 gene of avian Influenza A virus. Due the dynamic nature of the DNA molecules the local environment such as ion concentration, pH and temperature significantly influence its physical properties. We observed a decrease in DNA conductance of about 33% in high vacuum conditions. The counterion variation was analyzed by changing the buffer from sodium acetate to tris(hydroxymethyl) aminomethane, which resulted in a two orders of magnitude increase in the conductivity of the DNA. The fabrication of large array of identical SWNT nanoelectrodes was achieved by using ultralong SWNTs. Using these nanoelectrode array we have investigated the sequence dependent charge transport in DNA. A systematic study performed on PolyG - PolyC sequence with varying number of intervening PolyA - PolyT pairs showed a decrease in electrical signal from 180 pA (PolyG - PolyC) to 30 pA with increasing number of the PolyA - PolyT pairs. This work also led to the development of ultrasensitive nanoelectrodes based on enzyme functionalized vertically aligned high density multiwalled CNTs for electrochemical detection of cholesterol. The nanoelectrodes exhibited selectively detection of cholesterol in the presence of common interferents found in human blood.

Multifunctional nanoparticles in cancer: In vitro characterization, in vivo distribution, and cellular response after laser-NIR dye-induced heating

A novel biocompatible and biodegradable polymer, termed poly(Glycerol malate co-dodecanedioate) (PGMD), was prepared by thermal condensation method and used for fabrication of nanoparticles (NPs). PGMD NPs were prepared using the single oil emulsion technique and loaded with an imaging/hyperthermia agent (IR820) and a chemotherapeutic agent (doxorubicin, DOX). The size of the void PGMD NPs, IR820-PGMD NPs and DOX-IR820-PGMD NPs were approximately 90 nm, 110 nm, and 125 nm respectively. An acidic environment (pH=5.0) induced higher DOX and IR820 release compared to pH=7.4. DOX release was also enhanced by exposure to laser, which increased the temperature to 42°C. Cytotoxicity of DOX-IR820-PGMD NPs was comparable in MES-SA but was higher in Dx5 cells compared to free DOX plus IR820 (p<0.05). The combination of hyperthermia (HT) and chemotherapy improved cytotoxicity in both cell lines. We also explored the cellular response after rapid, short-term and low thermal dose (laser/Dye/NP) induced-heating, and compared it to slow, long-term and high thermal dose cell incubator heating by investigating the reactive oxygen species (ROS) level, hypoxia-inducible factor-1&agr; (HIF-1&agr;) and vascular endothelial growth factor (VEGF) expression. The cytotoxicity of IR820-PGMD NPs after laser/Dye/NP HT resulted in higher cancer cell killing compared to incubator HT. ROS level, HIF-1&agr; and VEGF expression were elevated under incubator HT, while maintained at the baseline level under the laser/Dye/NP HT. In vivo mouse studies showed that NP formulation significantly improved the plasma half-life of IR820 after tail vein injection. Significant lower IR820 content was observed in kidney in DOX-IR820-PGMD NP treatment as compared to free IR820 treatment in our biodistribution studies (p<0.05). In conclusion, both IR820-PGMD NPs and DOX-IR820-PGMD NPs were successfully developed and used for both imaging and therapeutic purposes. Rapid and short-term laser/Dye/NP HT, with a low thermal dose, did not up-regulate HIF-1&agr; and VEGF expression, whereas slow and long-term incubator HT, with a high thermal dose, can enhance expression of both HIF-1&agr; and VEGF.^

Análise de tensões integrada a sistema de engenharia reversa para projeto e confecção de próteses

This work consists of the conception, developing and implementation of a Computational Routine CAE which has algorithms suitable for the tension and deformation analysis. The system was integrated to an academic software named as OrtoCAD. The expansion algorithms for the interface CAE genereated by this work were developed in FORTRAN with the objective of increase the applications of two former works of PPGEM-UFRN: project and fabrication of a Electromechanincal reader and Software OrtoCAD. The software OrtoCAD is an interface that, orinally, includes the visualization of prothetic cartridges from the data obtained from a electromechanical reader (LEM). The LEM is basically a tridimensional scanner based on reverse engineering. First, the geometry of a residual limb (i.e., the remaining part of an amputee leg wherein the prothesis is fixed) is obtained from the data generated by LEM by the use of Reverse Engineering concepts. The proposed core FEA uses the Shell's Theory where a 2D surface is generated from a 3D piece form OrtoCAD. The shell's analysis program uses the well-known Finite Elements Method to describe the geometry and the behavior of the material. The program is based square-based Lagragean elements of nine nodes and displacement field of higher order to a better description of the tension field in the thickness. As a result, the new FEA routine provide excellent advantages by providing new features to OrtoCAD: independency of high cost commercial softwares; new routines were added to the OrtoCAD library for more realistic problems by using criteria of fault engineering of composites materials; enhanced the performance of the FEA analysis by using a specific grid element for a higher number of nodes; and finally, it has the advantage of open-source project and offering customized intrinsic versatility and wide possibilities of editing and/or optimization that may be necessary in the future

Estudo da adição de resíduos de quartzitos para obtenção de grés porcelanato

In States of Paraíba (PB) and Rio Grande do Norte (RN), northeast of Brazil, the most significant deposits of non-metallic industrial minerals are pegmatites, quartzites and granites, which are located in Seridó region. Extraction of clay, quartz, micas and feldspars occurs mainly in the cities of Várzea (PB), OuroBranco (RN) and Parelhas (RN). Mining companies working in the extraction and processing of quartzite generate large volumes of waste containing about 90% SiO2 in their chemical composition coming from quartz that is one of the basic constituents of ceramic mass for the production of ceramic coating. Therefore, this work evaluates the utilization of these wastes on fabrication of high-quality ceramic products, such as porcelain stoneware, in industrial scale. Characterization of raw materials was based on XRF, XRD, GA, TGA and DSC analysis, on samples composed by 57% of feldspar, 37% of argil and 6% of quartzite residues, with 5 different colors (white, gold, pink, green and black). Samples were synthesized in three temperatures, 1150°C, 1200°C and 1250°C, with one hour isotherm and warming-up tax of 10°C/min. After synthesizing, the specimens were submit to physical characterization tests of water absorption, linear shrinkage, apparently porosity, density, flexural strain at three points. The addition of 6% of quartzite residue to ceramic mass provided a final product with technological properties attending technical norms for the production of porcelain stoneware; best results were observed at a temperature of 1200°C. According to the results there was a high iron oxide on black quartzite, being their use in porcelain stoneware discarded by ethic and structural question, because the material fused at 1250°C. All quartzite formulations had low water absorption when synthesized at 1200°C, getting 0.1% to 0.36% without having gone through the atomization process. Besides, flexural strain tests overcame 27 MPa reaching the acceptance limits of the European Directive EN 100, at 1200°C synthesizing. Thus, the use of quartzite residues in ceramic masses poses as great potential for the production of porcelain stoneware.

Influência da absorção de umidade no comportamento mecânico nos compósitos poliméricos híbridos Kevlar/vidro quando imerso em água do mar e petróleo

The polymer matrix composite materials are being used on a large scale in the most different industrial fields such as aerospace, automotive, oil, among others, since the industrial perspectives is currently working with materials which have a good mechanical performance at high service life and cost / benefit. Thus, the determination of the mechanical properties is indispensable for the characterization of waste resulting in greater expansion of this type of material. Thus, this work will be obtained three plates laminated with tereftálica polymeric matrix reinforced by a bidirectional woven E-glass and kevlar both industrially made, where the plates are manufactured by manual lamination process (hand lay-up), all laminates have five enhancement layers, the first hybrid laminate will consist of bidirectional woven E-glass fiber, kevlar fiber interspersed with layers, is formed by the second bidirectional woven kevlar fiber at the ends of the laminate (two layers), and in the center the glass fiber fabric (three layers), the third plate is composed of only the bidirectional woven E-glass fiber. Then were prepared specimens (CP) by standard, to determine the mechanical properties of tensile and bending in three points. After fabrication of the specimens, they were immersed in oil and seawater. After that, there was a comparison of the mechanical properties for the test condition in the dry state. Showing that there was a considerable increase in the properties studied because the effect of hybridization in laminates.

Utilização do titâneo na confecção de estruturas metálicas em prótese parcial removível

Due to properties such as excellent biocompatibility, high resistance to corrosion and low specific weight, titanium has been considered a material of great interest for Dentistry. It has been widely used in implants and orthognathic surgeries. Recently, titanium has been seen as a feasible alternative for the fabrication of removable partial denture frameworks, either in pure titanium (99.75%) or in titanium alloy forms (Ti-6Al-4V; Ti-6A1-7Nb). Based on a review of the literature, this work studied the use of titanium for the fabrication of removable partial denture frameworks, focusing on its advantages and disadvantages as well as its characteristics. It was concluded that the use of titanium is a convenient option for partially edentulous arches rehabilitation with quite satisfactory and promising clinical results. However, the need for highly-equipped laboratories increases the cost, preventing its large scale use.

Utilização do titâneo na confecção de estruturas metálicas em prótese parcial removível

Due to properties such as excellent biocompatibility, high resistance to corrosion and low specific weight, titanium has been considered a material of great interest for Dentistry. It has been widely used in implants and orthognathic surgeries. Recently, titanium has been seen as a feasible alternative for the fabrication of removable partial denture frameworks, either in pure titanium (99.75%) or in titanium alloy forms (Ti-6Al-4V; Ti-6A1-7Nb). Based on a review of the literature, this work studied the use of titanium for the fabrication of removable partial denture frameworks, focusing on its advantages and disadvantages as well as its characteristics. It was concluded that the use of titanium is a convenient option for partially edentulous arches rehabilitation with quite satisfactory and promising clinical results. However, the need for highly-equipped laboratories increases the cost, preventing its large scale use.