Refereed Articles
  1. Ronnander, P., Simon, L., Spilgies, H, Koch, A. and Scherr, S. (2017), Dissolving polyvinylpyrrolidone-based microneedle systems for in-vitro delivery of sumatriptan succinate, European Journal of Pharmaceutical Sciences, 114, 84-92.

    A new dissolving, biodegradable microneedle array system was developed as a suitable alternative delivery method of sumatriptan for the relief of migraine. The microneedles were formulated with a polyvinylpyrrolidone polymer to deliver encapsulated sumatriptan succinate into the skin and dermis layers for rapid distribution into the body fluid. Sumatriptan microneedle in-vitro diffusion studies with G÷ttingen minipig skins indicate that a 10.7 cm2 microneedle array patch could provide the required bioavailability and therapeutic effect for at least 7 hours.

  2. Simon, L. (2017), An effective time-constant algorithm for drug transport to capillaries and surrounding tissues, Computers in Biology and Medicine, 89, 24-30.

    A new procedure is outlined to estimate the time it takes to reach equilibrium concentrations in capillaries and neighboring tissues. Using a Krogh cylinder model, one- and two-dimensional analytical solutions were derived to monitor the amount of drug released in the tissue. The methodology employed has several potential applications in biotransport, including the development of a framework to analyze the dynamics of oxygen uptake in peripheral nerves.

  3. Simon, L. (2017), A Laplace transform-based technique for solving multiscale and multidomain problems: Application to a countercurrent hemodialyzer model, Computers in Biology and Medicine, 87, 230-235.

    We propose a new procedure to evaluate the dynamic and steady-state behaviors of a countercurrent hemodialyzer model. The effort may aid physicians in providing an optimal dialysis prescription. While considerable research has focused on understanding key factors contributing to the development and consequences of kidney disease, less attention has been devoted to the applications of mathematical tools. Such resources would help investigators answer significant questions relevant to clinicians, patients and practitioners.

  4. Voronov, R.S.*, Basuray, S., Obuskovic, G., Simon, L., Barat, R.B. and Bilgili, E. (2017), Statistical analysis of undergraduate chemical engineering curricula of United States of America universities: Trends and observations, Education for Chemical Engineers, 20, 1-10.

  5. Simon, L.* and Ospina, J. (2017), A two-dimensional description of absorption in humans after dermal exposure to volatile organic compounds,Chemical Engineering Communications,  204, 698-704.

    A two-dimensional diffusion model was developed to predict the absorption of chemicals in humans following dermal contact. A first-order evaporation rate equation was applied to the skin surface while a perfect-sink boundary condition was imposed at the skin/capillary interface. This work will allow researchers to simulate two-dimensional diffusion of a chemical into the skin and assess the effects of volatility and exposure time.

  6. Simon, L.* and Ospina, J. (2016), A three-dimensional semi-analytical solution for predicting drug release through the orifice of a spherical device, International Journal of Pharmaceutics, 509, 477-482.

    A three-dimensional drug transport through a spherical liposomal vesicle was studied. The governing equation was derived using the Fick’s second law. A mixed Neumann-Dirichlet condition was imposed at the boundary to represent diffusion through only a small region on the surface of the device. The effective time constant was derived to estimate the time required for releasing ninety-eight percent of the amount of drug.

  7. Simon, L.* and Ospina, J. (2016), The development of a peak-time criterion for designing controlled-release devices, European Journal of Pharmaceutical Sciences, 91, 64-73.

    A new strategy was developed to predict the maximum flux and time-to-peak for drugs released through controlled-release (CR) devices with a finite donor volume. Much interest in bioequivalence studies has been directed toward understanding the area under the plasma concentration-time curve (AUC), the peak-height concentration (Cmax ) and the time to reach Cmax (tmax). The peak-height concentration must be achieved for a patient to respond adequately to a medication. If one considers the minimum effective concentration (MEC), the evaluation of tmax helps clinicians decide which formulation to recommend. However, no similar studies have been performed for CR systems which often exhibit a peak flux depending on the amount of drug in the formulation vehicle (e.g., finite donor volume). This contribution proposed a method to estimates the peak flux and time-to-peak of CR models in terms of critical process parameters, such as the diffusion and partition coefficients.

  8. Simon, L.* and Ospina, J. (2016), On the effusion time of drugs from the open pore of a spherical vesicle, Physica A: Statistical Mechanics and its Applications, 451, 366-372.

    There is consederable interest in understanding how drug molecules are transported through liposomal surface pores. But only a few theoretical studies have focused on the release bahavior. A modeling and simulation platform would help manufacturers assess the specific role of each mechanism (e.g., permeation through the membrane and release from the pores). This contribution offers a method that would make it possible to evaluate several designs at a rather inexpensive cost. Valuable insight into the physical phenomenon is provided.

  9. Simon, L.*, Ospina, J. and Ita, K. (2015), Prediction of in-vivo iontophoretic drug release data from in-vitro experiments - Insights from modeling, Mathematical Biosciences, 270, 106-114.

    A new strategy was developed to predict in-vivo plasma drug levels from data collected during in-vitro transdermal iontophoretic delivery. The method used the principle of mass conservation and the Nernst-Planck flux equation to describe molecular transport across the skin. Distribution and elimination of the drug in the body followed a one- or two-compartment open model. This contribution also develops analytical expressions for the relaxation constant and plasma drug concentration.

  10. Simon, L.* and Ospina, J. (2015), Three-dimensional analyses of a perforated cylindrical drug delivery device, International Journal of Pharmaceutics, 481, 64-70.

    The system studied is a cylindrical, monolithic structure which contains an active agent. The device is covered with an impermeable coating substance and the medication is released through a small cylindrical rectangle located on the lateral surface. This work may help researchers estimate physicochemical parameters from laboratory experiments, and fabricate implants for long-term delivery.

  11. Kim, K.S., Ita, K. and Simon, L.* (2015), Modelling of dissolving microneedles for transdermal drug delivery: theoretical and experimental aspects, European Journal of Pharmaceutical Sciences, 68, 137-143.

    Soluble microneedles (MNs) continue to attract considerable interest in the research community because of clinical advantages, such as painless administration and minimal invasiveness. A mathematical model was built to predict the amount of drug delivered into the skin via dissolution of the needle. This algorithm is intended to provide a useful tool for simulating drug release from the device.

  12. Ferreira, J.A,, de Oliveira, P.*, da Silva, P.M. and Simon, L. (2014), Molecular transport in viscoelastic materials: mechanistic properties and chemical affinities, SIAM
    Journal on Applied Mathematics
    , 74, 1598–1614.

    The preprint can be downloaded from: http://www.mat.uc.pt/preprints/ps/p1423.pdf.

  13. Stukel, J, Thompson, S., Simon, L. and Willits, R.* (2015), Polyethlyene glycol microgels to deliver bioactive nerve growth factor, Journal of Biomedical Materials Research, 103, 604-613.
  14. Simon, L.*, Ospina, J. and Willits, R.K. (2014),The dynamics of shrinking and expanding drug-loaded microspheres: A semi-empirical approach, European Journal of Pharmaceutical Sciences, 58, 55-62.

    This study allows researchers to study molecular transport through shrinking and expanding drug-loaded microspheres. The effects of the rate and degree of swelling on drug release from hydrogels can be simulated easily. The time it takes to deliver the API is also estimated. This effective time constant can be instrumental in the selection of components, such as monomers and cross linkers. The proposed analytical method is tested on the release of insulin from swelling Ca-alginate beads.

  15. Simon, L.* and Ospina, J. (2013), Two-dimensional transport analysis of transdermal drug absorption with a non-perfect sink boundary condition at the skin-capillary interface, Mathematical Biosciences, 244, 58-67.

    This work provides a clear picture of the distribution of timolol, a beta-blocker, in the skin layers. The analytical platform is suitable for simulating the absorption of topical medications, estimating key formulation parameters and manufacturing devices that meet specific requirements. A virtual environment is created that will help predict patch performances, at early design stages, and determine the time elapsed before reaching a desired delivery rate.

  16. Simon, L.* and Ospina, J. (2014), A First-order time constant estimation for nonlinear diffusion problems, Chemical Engineering Communications, 201, 719-736.

    A new design tool is proposed to accelerate the production of robust, reliable and low-cost biosensors. The contribution of factors, such as membrane thickness, substrate concentration and the enzymatic reaction rate can be assessed in the early stage of development. Two case studies are considered to explain the method: a nonlinear heat equation and a reaction-diffusion model with Michaelis–Menten-type kinetics.


  17. An approach, based on replacement methods and artificial neural networks, is proposed to identify chemicals that improve skin permeability. The study may help with the transdermal delivery of large drug molecules. 

  18. Simon, L.* and Ospina, J. (2013), Two-dimensional solution and analysis of a cylindrical matrix device with a circular release area, Chemical Engineering Communications, 200, 115-138.

    A controlled delivery system, e.g., a transdermal patch or an implant, may help patients adhere to a prescribed drug regimen. The initial dose, delivery rate and time it takes to release the total amount of the active pharmaceutical ingredient (API) are important factors that influence the development of these systems. A method is provided to monitor device performance, even during the early stages of development, and tailor design specifications to end-user requirements.

  19. Wei, R., Simon, L.*, Hu, L. and Michniak-Kohn, B. (2012), Effects of iontophoresis and chemical enhancers on the transport of lidocaine and nicotine across the oral mucosa, Pharmaceutical Research, 29, 961-971.

    The effects of chemical enhancers and iontophoresis on the buccal transmucosal delivery of lidocaine and nicotine were investigated. A numerical procedure that allowed for a systematic approach to design chemical and physical penetration enhancers was implemented. An increase in the flux does not necessarily reduce the time it takes to reach the steady-state value. This approach is of great interest to all scientists working on controlled release systems and will help in the development of oral transmucosal devices.


  20. Despite the growing popularity of transdermal patches, it can be difficult to predict their performance without a basic knowledge of contributing transport mechanisms and important properties of the membranes. Topics, such as how long it takes to reach the desired delivery rate and the time required to release the drug from the patch are discussed in this contribution. User-friendly mathematical expressions are developed. Note: The article can be downloaded from the Pharmaceutics website.  

  21. Kim, K.S. and Simon, L.* (2012), Application of a dissolution-diffusion model to the release of 5-fluorouracil from polymer microspheres, Chemical Engineering Communications, 199, 587-599.

    The main purpose of this investigation is to broaden the applications of controlled-release technology to include treatment for colorectal cancers or other types of malignancies by 1) unraveling the transport mechanism of 5-FU-loaded microspheres, 2) identifying the critical factors that contribute to the release of 5-FU from microspheres and 3) providing optimal device-design guidelines to manufacturers. Product developers and clinicians will apply the theoretical approach to discover design parameters, reduce cost and improve the effectiveness of existing devices. An interactive and remote access program is also provided to help clinicians devise effective treatment strategies for individual patients and facilitate the development of affordable technologies that reduce side-effects: http://webmath.njit.edu/webMathematica/mathsimon/Microsphere1.jsp

  22. Ferreira, J.A., de Oliveira, P.*, da Silva, P. and Simon, L. (2011), Flux tracking in drug delivery, Applied Mathematical Modelling, 35, 4684-4696.

    The preprint can be downloaded from: http://www.mat.uc.pt/preprints/ps/p1013.pdf.

  23. Simon, L. (2012), Graphical process design tools for iontophoretic transdermal drug-delivery devices, Computer Methods and Programs in Biomedicine, 107, 447-455.

    The application of low-intensity current on a patch increases the permeation of molecules through the skin and provides an accurate method to control plasma levels of a drug. This article proposes a procedure to help select the loading dose and current density. The graphical approach outlined is simple and allows users to achieve a desired concentration in a relatively short time.

  24. Kim, K.S. and Simon, L.* (2011), Modeling and design of transdermal drug delivery patches containing an external heating device, Computers & Chemical Engineering, 35, 1152-1163.

    The risks and benefits of heat exposure to patches are documented in several reports. While accidents such as drug overdose may occur in patients wearing transdermal patches, research clearly shows that the technology is promising and can be applied to regulate the dermal delivery of pain medicines. Products, approved by the Food and Drug Administration (FDA), use the method to administer local analgesia to adults and children. This article offers a road map for designing effective heat-induced controlled release devices.

    The article is featured in the July 2011 issue of NewsRX.

    .

    This contribution is selected as an "Editor's Choice" in the June/July 2011 issue of Pharmaceutical Formulation & Quality.

  25. Kim, K.S. and Simon, L.* (2011), Transport mechanisms in oral transmucosal drug delivery: Implications for pain management, Mathematical Biosciences, 229, 93-100.

    i) Science Direct Top 25 Hottest Articles - Agricultural and Biological Sciences - Mathematical Biosciences; January - December 2011

    ii) Science Direct Top 25 Hottest Articles - Agricultural and Biological Sciences - Mathematical Biosciences; October - December 2011

    Oral transmucosal drug delivery focuses on the administration of medicine through the mucus layer in the mouth. Advantages of this route include reduced enzymatic activity, ease of administration, avoidance of first-pass hepatic metabolism and high permeability compared to the human skin. The emerging technology has been used in the form of a lollipop-like lozenge placed between the cheek and the gum (e.g., Actiq® by Cephalon Inc.). This article offers a detailed study of the main factors that direct the transport of fentanyl citrate through the membrane and absorption into the bloodstream. The effects of accidental swallowing of the drug are included in the model.

    .

    The article is featured in the February 2011 issue of NewsRX.

  26. Simon, L.*, Kim, K.S. and Kanneganti, K. (2011), Effects of epidermal turnover on the dynamics of percutaneous drug absorption, Mathematical Biosciences, 229, 16-21.

    It is common knowledge that the skin is continually renewing itself. The natural change, which protects the stratum corneum and other layers, has a notable influence on the penetration of some drugs into the skin (e.g., highly lipophilic, large-molecular-weight chemicals). This contribution studies the effects of the turnover on the time it takes to achieve a target delivery rate. The findings may help develop high-quality patches that meet design and performance standards.

    The article is featured in the February 2011 issue of NewsRX.  

  27. Kanneganti, K. and Simon, L.* (2011), Two-compartment pharmacokinetic models for Chemical Engineers, Chemical Engineering Education, 45, 101-105.

    The project is suitable for courses on process dynamics and control. While the activities suggested in the one-compartment laboratory experiment introduced concepts of pharmacokinetics and drug administration,  this contribution broadens the focus to include a more complex process, involving two units, where students are asked to describe the states of the system from first-principles knowledge. The two-compartment model also features balances on transient systems and offers the opportunity to study and monitor, in an experimental setting, the dynamic behaviors of interconnected units.  In addition, issues related to the application of Laplace transforms, to solve a system of ordinary differential equations, are addressed.      

  28. Simon, L.*, Bolisetty, P. and Erazo, M.N. (2011), Dynamics of dissolution and diffusion-controlled drug release systems , Current Drug Delivery, 8, 144-151.

    Pharmaceutical companies are seeking new ways to manage product life cycles by developing innovative controlled-release devices. The name of the game is generic defense through sound reformulation strategies… And for market innovators timing is everything! Pharmaceutical industries are focusing on hydrophilic matrices to reformulate the drug, provide once-a-day dosing and achieve a desired release profile. These materials present several advantages, such as a cost-effective manufacturing process and suitability for a host of active pharmaceutical ingredients. However, the influence of the pertinent decision parameters (i.e., product and process quality attributes) on the steady-state drug penetration rate is difficult to assess in the current framework. This contribution introduces tools to modulate the rate at which drug molecules dissolve and diffuse in a polymeric system.

    The article is featured in the April 2011 issue of NewsRX.  

  29. Simon, L.*, Kanneganti, K. and Kim, K.S. (2010), Drug transport and pharmacokinetics for Chemical Engineers, Chemical Engineering Education, 44, 262-266.

    Experiments in continuous-stirred vessels are conducted to introduce chemical engineering students to clinical pharmacokinetics. These activities are designed to enable students to use their knowledge of process dynamics in developing drug-dosage regimens that meet certain criteria. The projects can be incorporated into the curriculum to illustrate concepts learned in the classroom.
  30. Kimmel, H.*, Hirsch, L.S., Simon, L., Burr-Alexander, L. and Dave, R. (2009), Implementing concepts of pharmaceutical engineering into high school science classrooms, Chemical Engineering Education, 43, 187-193.

    A Research Experience for Teachers (RET) program, to help high school science and technology teachers develop and strengthen skills and knowledge in research, science and engineering, is described.
  31. Kim, K.S. and Simon, L.* (2009), Optimal intravenous bolus-infusion drug dosage regimen based on two-compartment pharmacokinetic models, Computers & Chemical Engineering, 33, 1212-1219.

    There has been much written about ongoing investigation of drug safety, efficacy, pharmacokinetics and pharmacodynamics as clinicians tirelessly work to assure proper dosage of medicaments for patients. However, what is conspicuously lacking from the literature is a balanced discussion of the need to develop a sound computational framework that helps to critically evaluate the results of clinical studies. In this paradigm, the challenges of accurately prescribing drug doses and times of intake can be thoroughly addressed. The Simon group brings to light the development of user-friendly computer software for facilitating the design of optimal drug-dosage regimens. These programs will not only save time and money but will make it easier for clinicians, who may not be familiar with advanced mathematical tools, to determine appropriate administration protocols that meet patient needs.
  32. Simon, L. (2009), Timely drug delivery from controlled-release devices: Dynamic analysis and novel design concepts, Mathematical Biosciences, 217, 151-158.

    Science Direct Top 25 Hottest Articles - Agricultural and Biological Sciences - Mathematical Biosciences; January - March 2009

    Chemical permeation enhancers (e.g. oleic acid, polyethylene glycol, ethanol, acetone, etc.) are currently used by pharmaceutical scientists to increase percutaneous absorption of the therapeutic agent in a drug. Flexible polymers, such as EUDRAGIT« release products, are developed to help design drug-delivery devices that match a targeted release profile. Heat-aided and electrically-assisted mechanisms have also been applied to overcome the resistance of the stratum corneum thereby increasing the number of drugs that are delivered transdermally. This article suggests a dynamic framework and novel design concepts that will facilitate the control of both the appropriate flux and the rate at which a desired effect is achieved.
     
  33. Simon, L.* and Goyal, A. (2009), Dynamics and control of percutaneous drug absorption in the presence of epidermal turnover, Journal of Pharmaceutical Sciences, 98, 187-204.

    Scheindlin wrote*: "Very few companies, even "big pharma," possess the know-how and equipment to deal with the unusual ingredients involved, to work out the parameters needed to obtain the desired absorption rates, and to assemble the patches. Therefore, development and manufacture of these products are generally outsourced." This contribution suggests an optimum treatment protocol for the transdermal delivery of local anesthetics even when epidermal turonover is likely to reduce their absorption into the systemic circulation. Instead of prescribing short- and long-acting drugs after surgery, a single medicament can be prescribed and administered in a manner to control chronic and breakthrough pain. The suggested method relies more on the dose and administration schedules than on the process-design parameters.
    *Transdermal drug delivery: PAST, PRESENT, FUTURE. Mol Interv. 2004 Dec; 4(6): 308-
    12.
  34. Simon, L. (2007), Repeated applications of a transdermal patch: analytical solution and optimal control of the delivery rate, Mathematical Biosciences, 209, 593-607.

    i) Science Direct Top 25 Hottest Articles - Agricultural and Biological Sciences - Mathematical Biosciences; April - June 2008

    ii) Science Direct Top 25 Hottest Articles - Agricultural and Biological Sciences - Mathematical Biosciences; January - March 2008

    iii) Science Direct Top 25 Hottest Articles - Agricultural and Biological Sciences - Mathematical Biosciences; July - September 2007

    Two important questions are answered in this article: 1) What happens to a drug following successive applications of a transdermal patch? 2) In lieu of allocating all the resources for the design of a patch to meet zero or first-order kinetics (or a preset delivery rate), is it possible to implement a drug delivery strategy that produces similar (if not superior) results using an existing patch? The findings of this research will surprise you!
  35. Simon, L. (2007), Analysis of heat-aided membrane-controlled drug release from a process control perspective, International Journal of Heat and Mass Transfer, 50, 2425-2433.

    In an article entitled: "Transdermal Market: The Future of Transdermal Drug Delivery Relies on Active Patch Technology*" Jason McKinnie (Pharmaceutical Research Analyst for Frost & Sullivan) discussed how some companies are now developing active patches that rely on external sources of energy, such as heat, to overcome limitations associated with passive patches. However, because these technologies can no longer be explained in terms of passive diffusion, the Simon group has deployed new analytical tools and constructed the necessary framework designed to help with the development of clinical trial simulations. Our method can assist in the selection of optimum dosing strategies and the best trial design among equally viable alternatives, thus alleviating costly production delays. This contribution addresses the effect of heat on the delivery of drugs across membranes. We also show that, when a specific sequence of temperatures is applied to the skin, a desired delivery rate is achieved in a relatively short period of time. This optimum temperature profile is generated by an in-house computer program written explicitly for this purpose.

    *
    Drug Delivery Technology, September 2006, Vol. 6, No. 8.
  36. Goyal, A. Mandapuram, S., Michniak, B. and Simon, L.* (2007), Application of orthogonal collocation and regression techniques for recovering parameters of a two-pathway transdermal drug-delivery model, Computers & Chemical Engineering, 31, 107-120.

    The estimation of critical pharmacokinetic parameters and the identification of drug delivery mechanisms are essential for medical breakthroughs. These initiatives are, however, cost- and time-prohibitive as they involve numerous laboratory experiments. This work proposes and tests computational methods to assess the contribution of particular pathways of transdermal drug penetration and to evaluate key physicochemical properties. The applications of this contribution range from cosmetic skin care to dermal toxicology.
  37. Gautam, S. and Simon, L.* (2007), Prediction of equilibrium phase compositions and ▀-glucosidase partition coefficient in aqueous two-phase systems, Chemical Engineering Communications, 194, 117-128.

    This contribution offers predictive tools inspired by advances in artificial intelligence computing and the thermodynamics of polymer solutions to model the partitioning of biomolecules in Aqueous Two-phase Separation System (ATPS). The work promotes the industrial implementation of ATPS-based protein separation.
  38. Gautam, S. and Simon, L.* (2006), Partitioning of ▀-glucosidase from Trichoderma reesei in poly(ethylene glycol) and potassium phosphate aqueous two-phase systems: Influence of pH and temperature, Biochemical Engineering Journal, 30, 104-108.

    Science Direct Top 25 Hottest Articles - Chemical Engineering - Biochemical Engineering Journal; April - June 2006

    Beta-glucosidase was optimized in an Aqueous Two-phase Separation System (ATPS) based on conditions such as pH and temperature. Although tested on this particular enzyme, the methodology outlined can be adopted to help meet the world demand for pharmaceutical enzymes.
  39. Simon, L.*, Weltner, A.W., Wang, Y. and Michniak, B. (2006), A parametric study of iontophoretic transdermal drug-delivery systems, Journal of Membrane Science, 278, 124-132.

    A method for extracting pertinent design information from iontophoretic transdermal delivery experiments is proposed and tested. The findings can help to accelerate the development and commercialization of iontophoretic products.
  40. Simon, L.* and Loney, N.W. (2005), An analytical solution for percutaneous drug absorption: Application and removal of the vehicle, Mathematical Biosciences, 197, 119-139.

    Science Direct Top 25 Hottest Articles - Agricultural and Biological Sciences - Mathematical Biosciences; October - December 2005

    The penetration and distribution of drugs in the skin following application and removal of transdermal patches is studied. A user-friendly platform was created to help pharmaceutical industries and researchers to conduct a quick performance assessment of drug-delivery devices with a minimum number of experiments saving both time and money. This research will help manufacturers of controlled release devices to get their products from R&D to full-scale manufacturing.
  41. Fernandes, M., Simon, L.* and Loney, N.W. (2005), Mathematical modeling of transdermal drug delivery systems: Analysis and applications, Journal of Membrane Science, 256, 184-192.

    Science Direct Top 25 Hottest Articles - Chemical Engineering - Journal of Membrane Science; April - June 2005

    A simulation environment is provided to investigate the relative impact of different physicochemical parameters on drug-release profiles. This research could lead to new formulation strategies to improve the safe delivery of a constant amount of drug through the skin.
  42. Loney, N.W.*, Huang, C. R. and Simon, L. (2005), Mathematical model of a counter current flow multi-fiber dialyzer, World Journal of Microbiology and Biotechnology, 21, 791-796.

    Factors affecting the design and operation of countercurrent flow dialyzers are studied. The ensuing knowledge can be used to achieve greater efficiency in the treatment of hemodialysis patients.
  43. Simon, L.* and Fernandes, M. (2004), Neural network-based prediction and optimization of estradiol release from ethylene-vinyl acetate membranes, Computers & Chemical Engineering, 28, 2407-2419.

    A central question in transdermal drug formulation technology is addressed: What are the key membrane and solvent properties necessary to achieve a specific drug-release rate? This contribution offers a methodology, tested using estradiol, that promotes the transdermal absorption of drugs and facilitates the design of customized patches to meet the daily needs of consumers.
  44. Simon, L.* and Gautam, S. (2004), Modeling continuous aqueous two-phase systems for control purposes, Journal of Chromatography A., 1043, 135-147.

    An analytical approach was proposed to help improve the efficiency and yield of large-scale biopharmaceutical protein purification in aqueous biphasic systems (ATPS). The simulation platform makes it easy to identify, with minimal experimental trials, the optimal operating conditions for multi-component proteins. This approach has the potential to reduce production costs.
  45. Simon, L. (2005), Observing biomass concentration in a fixed-bed bioreactor, Chemical Engineering Communications, 192, 272-285.

    This contribution focuses on the use of engineering-based strategies to improve pollutant removal efficiency in tubular-fixed bed bioreactors. Immediate industrial applications include the optimization of the rate of contaminant degradation in full-scale biofilters.
  46. Karim, M.N.*, Hodge, D. and Simon, L. (2003), Data-based modeling and analysis of bioprocesses: some real experiences, Biotechnology Progress, 19,1591-1605.

    The use of advanced computational schemes, such as artificial neural networks and principal component models, in industrial settings are addressed in this contribution. These tools allow for quick data interpretation and the detection of trends and significant correlations among pertinent process variables. The result is a considerable reduction in the time-to-market of new products.
  47. Simon, L.* and Loney, N.W. (2003), Mathematical modeling and process control of distributed parameter systems, Chemical Engineering Education, 37,126-131.

    An application of Process Control principles relevant to distributed parameter systems, such as transdermal delivery of drugs, is outlined. The time required to reach a desired in-vivo flux can be estimated. This information plays a critical role in topical drug formulation and product development.
  48. Loney, N.W.*, Simon, L. and Gao, L. (2003), Trends in the applications of neural networks in chemical process modeling, Proceedings of the IndianNational Science Academy Part A (Physical Sciences), 69, 285-299.

    Although Artificial Neural network-based modeling is widespread among academicians, the pharmaceutical industry has been reluctant to embrace it. This contribution outlines a range of relevant applications to promote industrial collaboration and acceptability.
  49. Simon, L. and Karim, M.N.* (2002), Control of starvation-induced apoptosis in CHO cell Cultures, Biotechnology and Bioengineering, 78, 645-657.

    This contribution answers a basic question: Can starvation-induced apoptosis be delayed via manipulation of certain amino acids? A new perspective, applicable to the real-time control of apoptosis in bioreactors, is gained with the potential of increasing large-scale production of pharmaceutical products.
  50. Simon, L. and Karim, M.N.* (2001), Identification and control of dissolved oxygen in hybridoma cell culture in a shear sensitive environment, Biotechnology Progress, 17, 634-642.

    The productivity of mammalian cells is increased by ensuring an optimum supply of oxygen in the bioreactor. The procedures outlined have immediate application for bio-based industrial products and may help pharmaceutical plants to comply with GMP requirements.
  51. Simon, L. and Karim, M.N.* (2001), Probabilistic Neural Networks using Bayesian decision strategies and a modified Gompertz model for growth phase classification in the batch culture of Bacillus subtilis, Biochemical Engineering Journal, 7, 41-48.

    Reliable tools for accurate classification of growth cycles (i.e., lag, logarithmic, or stationary phase) in industrial fermentation processes are developed and tested using a B. subtilis strain. This work paves the way for cost-competitive fermentation technologies and allows for the timely addition of inducers in culture media.
  52. Simon, L., Karim, M.N.*, and Schreweis, A. (1998), Prediction and classification of different phases in a fermentation using Neural Networks, Biotechnology Techniques, 12, 301-304.

    The growth cycles (i.e., lag, logarithmic, or stationary phase) in industrial fermentation processes are predicted (and correctly classified) within the first few hours. The operator can make informed decisions at an early stage in the process, which may save a pharmaceutical company millions of dollars.
  53. Simon, L. and Loney, N.W.* (1996), An analytical solution for the concentration profile of a sublation process, Separation Science and Technology, 31,1019-1024.

    An engineering-based approach to remove pollutant from wastewater is described. The performance of the aerator apparatus used can be evaluated a priori. This tool will assist companies to meet regulatory compliance requirements.



    *Corresponding author
Content Copyright © 2010  Laurent Simon, Ph.D.   Site Design Copyright © 2010 SABERLIGHT
Site Map