Henrique A. Matos

Formation of indomethacin–saccharin cocrystals using supercritical fluid technology

The main objective of the present work is to check the feasibility of supercritical fluid (SCF) technologies in the screening and design of cocrystals (novel crystalline solids). The cocrystal formation tendencies in three different SCF techniques, focusing on distinct supercritical fluid properties - solvent, anti-solvent and atomization enhancer - were investigated. The effect of processing parameters on the cocrystal formation behaviour and particle properties in these techniques was also studied. A recently reported indomethacin-saccharin (IND-SAC) cocrystalline system was our model system. A 1:1 molar ratio of indomethacin (gamma-form) and saccharin was used as a starting material. The SCF techniques employed in the study include the CSS technique (cocrystallization with supercritical solvent), the SAS technique (supercritical anti-solvent), and the AAS technique (atomization and anti-solvent). The resulting cocrystalline phase was identified using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform-Raman (FT-Raman). The particle morphologies and size distributions were determined using scanning electron microscopy (SEM) and aerosizer, respectively. The pure IND-SAC cocrystals were obtained from SAS and AAS processes, whilst partial to no cocrystal formation occurred in the CSS process. However, no remarkable differences were observed in terms of cocrystal formation at different processing conditions in SAS and AAS processes. Particles from CSS processes were agglomerated and large, whilst needle-to-block-shaped and spherical particles were obtained from SAS and AAS processes, respectively. The particle size distribution of these particles was 0.2-5microm. Particulate IND-SAC cocrystals with different morphologies and sizes (nano-to-micron) were produced using supercritical fluid techniques. This work demonstrates the potential of SCF technologies as screening methods for cocrystals with possibilities for particle engineering.

Microcomposites theophylline/hydrogenated palm oil from a PGSS process for controlled drug delivery systems

Abstract New controlled-release carriers of theophylline prepared with hydrogenated palm oil (HPO) were obtained by Particles from gas saturated solutions (PGSS) at different working pressures. Pressure had no significant effect on the mean diameter of the particles (of about 3.0 μm). However, spherical morphology with a regular surface was preferentially obtained at higher expansion pressures. HPLC analysis revealed a low theophylline encapsulation in the HPO matrix and showed that considerable amounts of theophylline were located at the particles’ surface. Dissolution studies showed that theophylline released from the HPO matrix follows Higuchis model for simple diffusional processes. However, successful correlation with experiment was achieved only with the Brophy and Deasy long-time correction to the Higuchi equation.

Improvements for mass-exchange networks design

This paper addresses minimum utility cost mass-exchange network design by considering the special case of water minimisation. Two different situations are considered, re-use and regeneration re-use for single contaminants. For re-use, three different methods of targeting are presented, one of them being simultaneously a design method. This novel design method has the advantage of considering flowrate constraints only in the final stage of design. The concept of multiple pinches is introduced to prevent designing networks that do not lead to minimum cost distributed effluent treatment systems. For regeneration re-use, this paper presents the first known algorithm for targeting minimum water consumption in all possible situations. The targeted flowrate is then used to design the mass-exchange network, that almost always features splitting of operations.

Phase equilibria of natural flavours and supercritical solvents

Abstract To study the possibility of separation of cineole from limonene (two of the main components of eucalyptus oil) we measured the vapour-liquid equilibrium of the systems containing either d-limonene or 1, 8-cineole in the supercritical solvents carbon dioxide (at 318.2 and 323.2 K) and an azeotropic mixture of ethane+carbon dioxide (at 303.2 K). The results obtained show that both solutes have similar solubilities in the supercritical solvents studied here.

Dynamic modelling and scheduling of an industrial batch system

Abstract This paper addresses the optimal schedule of a resource constrained four-batch digester system of an industrial acid sulphite pulp mill. This involves the development of two different models, one to model the scheduling operational problem and the other the batch digester operation—process model. The first model uses a discrete-time Resource Task Network (RTN) based representation leading to a Mixed Integer Linear Program (MILP) formulation. In this, the main operational limitation, steam availability, is modelled through the definition of a superstructure including the most relevant heating alternatives. The duration of the generated heating tasks was estimated through the use of the process model—a distributed heterogeneous dynamic model in gPROMS, with a heat-transfer resistance at the solid–fluid-interface—validated with experimental plant data. The optimal schedules obtained showed that an increase in the total available steam from the boiler is vital to allow a higher level of productivity and that not much can be done regarding steam sharing improvements.

Development of a novel mucosal vaccine against strangles by supercritical enhanced atomization spray-drying of Streptococcus equi extracts and evaluation in a mouse model

Strangles is an extremely contagious and sometimes deadly disease of the Equidae. The development of an effective vaccine should constitute an important asset to eradicate this worldwide infectious disease. In this work, we address the development of a mucosal vaccine by using a Supercritical Enhanced Atomization (SEA) spray-drying technique. Aqueous solutions containing the Streptococcus equi extracts and chitosan were converted into nanospheres with no use of organic solvents. The immune response in a mouse model showed that the nanospheres induced a well-balanced Th1 and Th2 response characterized by a unitary ratio between the concentrations of IgG2a and IgG1, together with IgA production. This strategy revealed to be an effective alternative for immunization against S. equi, and therefore, it may constitute a feasible option for production of a strangles vaccine.

Univariate parameterization for global optimization of mixed-integer polynomial problems

This paper presents a new relaxation technique to globally optimize mixed-integer polynomial programming problems that arise in many engineering and management contexts. Using a bilinear term as the basic building block, the underlying idea involves the discretization of one of the variables up to a chosen accuracy level (Teles, J.P., Castro, P.M., Matos, H.A. (2013). Multiparametric disaggregation technique for global optimization of polynomial programming problems. J. Glob. Optim. 55, 227–251), by means of a radix-based numeric representation system, coupled with a residual variable to effectively make its domain continuous. Binary variables are added to the formulation to choose the appropriate digit for each position together with new sets of continuous variables and constraints leading to the transformation of the original mixed-integer non-linear problem into a larger one of the mixed-integer linear programming type. The new underestimation approach can be made as tight as desired and is shown capable of providing considerably better lower bounds than a widely used global optimization solver for a specific class of design problems involving bilinear terms.

Design of sustainable processes: Systematic generation & evaluation of alternatives

Abstract The objective of this paper is to present a new generic and systematic methodology for identifying the feasible design (retrofit) potential of any chemical process. The methodology determines a, series of mass and energy indicators (through simple calculations using steady state process data), establishes the operational and design targets, and through sensitivity based analysis, identifies, the design alternatives that can match the established design targets. The significance of this indicator-based method is the possibility to direct all the contradicting criteria (factors) to move in the same direction, thereby eliminating the need to identify trade-off based solutions. Finally, the indicators also reduce (where feasible) the safety indicators because the conditions of operation become less extreme. A new indicator sensitivity analysis algorithm has been added to the methodology to define design targets and to generate sustainable process alternatives. Through the process flowsheet for the production of Methyl Tertiary Butyl Ether, the application of the indicator based methodology is highlighted.

A Cost-Based Strategy to Design Multiple Shell and Tube Heat Exchangers

Process Integration has been applied in several industrial processes mainly using standard shell and tube heat exchangers (1-1 or 1-2). The flow arrangement in 1-2 multiple shell and tube heat exchangers involves part counter-current flow and part co-current flow. This fact is accounted for in the design by introducing a F T correction factor into the 1-1 heat exchanger design equation. To avoid some steep regions in the feasible space of heat exchangers design some authors introduce other parameters like Xp or G. Until now it was not possible to have an overall map to give some guidelines of how to choose between the several Xp approaches established in the literature. This paper summarizes the current existing criteria in a general design algorithm (DeAl 12 ) to show a path for the calculations of the main design variables of the heat exchanger. Also a new strategy design algorithm (StratDeAl 12 ) is introduced in this paper to allow the best choice between the existing Xp approaches based on the heat exchanger cost minimisation. Several examples illustrate the advantage of using the developed algorithm and the deviations obtained in the heat exchanger cost if a wrong approach was chosen.

Phase equilibria of ethene + limonene and ethene + cineole from 285 k to 308 k and pressures to 8 mpa

Abstract Using a variable-volume high pressure equilibrium cell, phase behaviour was obtained for the binaries supercritical ethene with limonene and supercritical ethene with cineole. VLE, including the mixture critical points, was obtained at 288 K, 298 K and 308 K and for pressures to 8 MPa. Liquid-liquid-vapour (LLV) equilibrium was found for both binaries above the critical temperature of ethene, in the range 285–301 K. The results indicate that at these experimental conditions both terpenes have similar phase behaviour with ethene. The measured VLE data were correlated using the Peng-Robinson equation of state using the two parameter unsymmetric mixing rules of Panagiotopoulos and Reid.