Papers by Miguel Rodrigues
Journal of Pharmaceutical Sciences, 2012
Monoclonal antibodies continue to command a large market for treatment of a variety of diseases. ... more Monoclonal antibodies continue to command a large market for treatment of a variety of diseases. In many cases, the doses required for therapeutic efficacy are large, limiting options for antibody delivery and administration. We report a novel formulation strategy based on dispersions of antibody nanoclusters that allows for subcutaneous injection of highly concentrated antibody (~190 mg/ml). A solution of monoclonal antibody 1B7 was rapidly frozen and lyophilized using a novel spiral-wound in situ freezing technology (SWIFT) to generate amorphous particles. Upon gentle stirring, a translucent dispersion of ~430 nm protein clusters low apparent viscosity (~24 cp) formed rapidly in buffer containing the pharmaceutically acceptable crowding agents, trehalose, polyethylene glycol and n-methyl-2-pyrrolidone. Upon in vitro dilution of the dispersion, the nanoclusters rapidly reverted to monomeric protein with full activity, as monitored by dynamic light scattering and antigen binding. When administered to mice as an intravenous solution, subcutaneous solution or subcutaneous dispersion at similar (4.6-7.3 mg/kg) or ultra-high dosages (51.6 mg/kg), the distribution and elimination kinetics were within error and the protein retained full activity. Overall, this method of generating high-concentration, low-viscosity dispersions of antibody nanoclusters could lead to improved administration and patient compliance, providing new opportunities for the biotechnology industry.
Journal of Nonlinear Science, 2014
Since its elaboration by Whitham, almost fifty years ago, modulation theory has been known to be ... more Since its elaboration by Whitham, almost fifty years ago, modulation theory has been known to be closely related to the stability of periodic traveling waves. However, it is only recently that this relationship has been elucidated, and that fully nonlinear results have been obtained. These only concern dissipative systems though: reaction-diffusion systems were first considered by Doelman, Sandstede, Scheel, and Schneider [Mem. Amer. Math. Soc. 2009], and viscous systems of conservation laws have been addressed by Johnson, Noble, Rodrigues, and Zumbrun [preprint 2012]. Here, only nondissipative models are considered, and a most basic question is investigated, namely the expected link between the hyperbolicity of modulated equations and the spectral stability of periodic traveling waves to sideband perturbations. This is done first in an abstract Hamiltonian framework, which encompasses a number of dispersive models, in particular the well-known (generalized) Korteweg-de Vries equation, and the less known Euler-Korteweg system, in both Eulerian coordinates and Lagrangian coordinates. The latter is itself an abstract framework for several models arising in water waves theory, superfluidity, and quantum hydrodynamics. As regards its application to compressible capillary fluids, attention is paid here to untangle the interplay between traveling waves/modulation equations in Eulerian coordinates and those in Lagrangian coordinates. In the most general setting, it is proved that the hyperbolicity of modulated equations is indeed necessary for the spectral stability of periodic traveling waves. This extends earlier results by Serre [Comm. Partial Differential Equations 2005], Oh and Zumbrun [Arch. Ration. Mech. Anal. 2003], and Johnson, Zumbrun and Bronski [Phys. D 2010]. In addition, reduced necessary conditions are obtained in the small amplitude
Journal of biomedical materials research. Part A, Jan 16, 2014
Polyvinyl alcohol hydrogel (PVA) is a water-soluble synthetic polymer that is commonly used in bi... more Polyvinyl alcohol hydrogel (PVA) is a water-soluble synthetic polymer that is commonly used in biomedical applications including vascular grafting. It was argued that the copolymerization of PVA with dextran (Dx) can result in improvement of blood-biomaterial interactions. The focus of this experimental study was to assess that interaction through an in vivo and in vitro evaluation of the coagulation system activation. The thrombogenicity of the copolymer was determined by quantification of platelet adhesion through the lactate dehydrogenase assay, determination of whole blood clotting time, and by quantification of platelet activation by flow cytometry. The thrombin-antithrombin complex blood levels were also determined. The obtained results for the in vitro assays suggested a non-thrombogenic profile for PVA/Dx. Additionally in vivo coagulation and hematological parameters were determined in an animal model after PVA/Dx vascular graft implantation. For coagulation homeostasis asse...
The Journal of Supercritical Fluids, 2010
The supercritical fluid enhanced atomization (SEA) process was used to produce cocrystals of six ... more The supercritical fluid enhanced atomization (SEA) process was used to produce cocrystals of six different active pharmaceutical ingredients (APIs): indomethacin, theophylline, caffeine, sulfamethazine, aspirin and carbamazepine. Micrometric cocrystals using the FDA-approved sweetener saccharin (SAC) as a cocrystal former were produced from ethanol solutions using supercritical CO 2 as the atomization enhancing fluid. The corresponding cocrystalline phases were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Particle morphologies and size distributions were analyzed by scanning electron microscopy (SEM) and by aerosizer. The results presented here show the formation of cocrystals of all the APIs selected, evidencing the ability and the potentiality of the SEA technique to generate different pharmaceutical cocrystals. Cocrystal particles produced by SEA had similar mean particle size than those produced by classical grinding methods. Interestingly, a new cocrystal form of theophylline-saccharin (likely with a 1:2 stoichiometry) was obtained by the SEA method that has not been previously reported by traditional screening methods.
The Journal of Supercritical Fluids, 2011
The Atomization of Supercritical Antisolvent Induced Suspensions (ASAIS) is a small volume superc... more The Atomization of Supercritical Antisolvent Induced Suspensions (ASAIS) is a small volume supercritical antisolvent process characterized by the inline dissolution of the antisolvent before the liquid atomization for the solvent extraction step. The antisolvent (CO 2) is mixed with the solute-containing solution in a small volume mixer immediately before the nozzle orifice in conditions such that cause the precipitation of the solutes. The generated suspension is then spray-dried for solvent separation. Compared to other similar particle-producing techniques, this approach allows a more efficient control of the antisolvent process and reduces the volume of the high-pressure precipitator by several orders of magnitude. Theophylline (TPL) particles produced by ASAIS are the polymorph previously obtained elsewhere by conventional SAS. Yet, the normal (non-polymorph) crystal form is obtained under non-antisolvent conditions. The required phase equilibria of the system TPL/tetrahydrofuran/CO 2 between 308 K and 328 K were also obtained. The results presented here demonstrate that, under selected conditions, ASAIS is a continuous-regime alternative to conventional SAS for the production of unique products, such as crystal polymorphs.
The Journal of Supercritical Fluids, 2007
Using the synthetic method, vapor-liquid equilibria near the critical points of tetrahydrofuran (... more Using the synthetic method, vapor-liquid equilibria near the critical points of tetrahydrofuran (THF)/carbon dioxide mixtures were determined at 313 K, 323 K and 333 K and at pressures from 6 MPa to 10 MPa. The volume expansion of THF in high-pressure CO 2 was measured in a high-pressure view cell at 308 K, 313 K and 318 K and at pressures from 1 MPa to 8 MPa. The correlation of the experimental VLE data with the Peng-Robinson equation of state and the Panagiotopoulos-Reid (P&R) mixing rules described better the experimental data than the same equation of state with the van der Waals one-fluid mixing rules. On the contrary, prediction of volume expansion data with van der Waals mixing rules agreed better with experimental data at low pressures than those predicted with the P&R mixing rules. The hydrogenated palm oil (HPO)/THF/CO 2 system was studied to produce particles of HPO using a supercritical antisolvent (SAS) atomization process. Results indicate that the morphology of the produced HPO particles ranged from spheres to fibers. A discussion is presented on the effects of the initial state of the CO 2 /THF mixture on the particle morphology based on the phase equilibrium behavior around the critical points of the binary THF/CO 2 mixtures, the atomization, and a differential scanning calorimetry (DSC) investigation. This discussion suggests that the initial state of the feed mixture determines the morphology of the produced particles-a two-phase vapor-liquid mixture favors the production of spheres due to atomization, whereas a mixture in a SCF state favors the formation of fibers due to crystallization.
Industrial & Engineering Chemistry Research, 2005
The Peng-Robinson equation of state (PR-EoS) and the Stryjek and Vera modification of the Peng-Ro... more The Peng-Robinson equation of state (PR-EoS) and the Stryjek and Vera modification of the Peng-Robinson equation of state (PRSV-EoS) were used to predict the vapor-liquid equilibrium of the system carbon dioxide(1)/ethanol(2)/water(3) under various temperatures and pressures. We propose a new algorithm that uses a flash calculation to provide a set of initial values and then solves the highly nonlinear phase equilibrium equations using the Broyden modified Newton-Raphson (BNR) method. With interaction parameters for the constituent binary systems, the ternary vapor-liquid equilibrium prediction shows that, at a given temperature, pressure, and water molar fraction in liquid phase, this algorithm is stable to calculate all other compositions. The calculated results from both the PR-EoS and the PRSV-EoS are in good agreement with the experimental data for the binary and ternary systems. A water removal process using supercritical carbon dioxide was experimentally implemented. The pressure dependence of the volume expansion of the mixture ethanol/water with carbon dioxide was also investigated using a high-pressure view cell. The established phase equilibrium calculation was applied to predict the volume expansion behavior and to evaluate the water removal efficiency. Results show that this ternary phase equilibrium calculation is useful to study the water removal process under high pressure carbon dioxide. It also shows that the volume expansion prediction is good at relatively low ethanol mass fraction in the feeding water/ethanol mixture or at low pressures.
Fluid Phase Equilibria, 2006
A conventional method was used to measure the melting points of the natural lipid tripalmitin and... more A conventional method was used to measure the melting points of the natural lipid tripalmitin and of the coenzyme ubiquinone (coQ10) under high pressure carbon dioxide. The pressuretemperature behavior of the binary three-phase solidliquidgas (SLG) ...
AIChE Journal, 2005
A particles from gas-saturated solution (PGSS) process for the model system hydro-genated palm oi... more A particles from gas-saturated solution (PGSS) process for the model system hydro-genated palm oil (HPO) with CO2 was implemented and particle information, including size, size distribution, and morphology, is reported. The PGSS process in a capillary nozzle is ...
2009 9th International Symposium on Communications and Information Technology, 2009
Spectrally Efficient non orthogonal Frequency Division Multiplexing (SEFDM) Systems occupy less b... more Spectrally Efficient non orthogonal Frequency Division Multiplexing (SEFDM) Systems occupy less bandwidth than equivalent orthogonal FDM (OFDM). However, enhanced spectral efficiency comes at the expense of an increased complexity in the signal detection. In this work, we present an overview of different detection techniques that trade the error performance optimality for the signal recovery computational effort. Linear detection methods like Zero Forcing (ZF) and Minimum Mean Squared Error (MMSE) offer fixed complexity but suffer from a significant degradation of the Bit Error Rate (BER). On the other hand optimal receivers like Sphere Decoders (SD) achieve the optimal solution in terms of error performance. Notwithstanding, their applicability is severely constrained by the SEFDM signal dimension, the frequency separation between the carriers as well as the noise level in the system.
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Papers by Miguel Rodrigues