Aleck H. Alexopoulos

Semi-batch emulsion copolymerization of vinyl acetate and butyl acrylate using oligomeric nonionic surfactants

Detailed kinetic studies on semi-batch emulsion copolymerization of vinyl acetate/butyl acrylate (VAc/BuA) (80xa0:xa020) at 80°C were carried out using alkyl polyglucoside nonionic surfactants and ammonium persulfate as initiator. The polymerization recipe was varied with respect to the amount of initiator initially charged and continuously fed to the reactor, the surfactant concentration, the electrolyte concentration, and the monomer addition rate. Various types of alkyl polyglucosides with different hydrophilic and hydrophobic chain lengths were tested. Latex particle stabilization was shown to depend significantly on the surfactant structure and its adsorption characteristics. In general, the latex particle size distribution evolved from a bimodal to a unimodal distribution while latex destabilization was observed at high surfactant or/and high initiator concentrations. Based on experimental observations it was found that the most important factor for imparting particle stability was the hydrophilic/hydrophobic chain length ratio of the surfactant which actually controlled the balance between surface coverage and stabilizing capability.

Particle Transfer and Deposition Using an Integrated CFD Model of the Respiratory System

Abstract The present work describes an integrated CFD model of the respiratory system from the nasal cavity down to the bronchioli. The model is comprised of nine sequential computational blocks corresponding to the nasal cavity, the pharyngo-trachea, and a series of branches in the pulmonary system. Steady-state turbulent flow is employed to describe the inspiration flow and deposition of particles of different sizes. Local deposition efficiency is found to increase with particle size and flow rate. The deposition profiles are in accordance to experimental and computational results available in the literature. The proposed integrated respiratory model describes the flow, penetration, and deposition of particles in the respiratory system accounting for the influence of the nasal cavity and the pulmonary branches.

Optimization of a DPI Inhaler: A Computational Approach

Alternate geometries of a commercial dry powder inhaler (DPI, i.e., Turbuhaler; AstraZeneca, London, UK) are proposed based on the simulation results obtained from a fluid and particle dynamic computational model, previously developed by Milenkovic etxa0al. The alternate DPI geometries are constructed by simple alterations to components of the commercial inhaler device leading to smoother flow patterns in regions where significant particle-wall collisions occur. The modified DPIs are investigated under the same conditions of the original studies of Milenkovic etxa0al. for a wide range of inhalation flow rates (i.e., 30-70 L/min). Based on the computational results in terms of total particle deposition and fine particle fraction, the modified DPIs were improved over the original design of the commercial device.

Computational model of particle deposition in the nasal cavity under steady and dynamic flow.

A computational model for flow and particle deposition in a three-dimensional representation of the human nasal cavity is developed. Simulations of steady state and dynamic airflow during inhalation are performed at flow rates of 9–60 l/min. Depositions for particles of size 0.5–20 μm are determined and compared with experimental and simulation results from the literature in terms of deposition efficiencies. The nasal model is validated by comparison with experimental and simulation results from the literature for particle deposition under steady-state flow. The distribution of deposited particles in the nasal cavity is presented in terms of an axial deposition distribution as well as a bivariate axial deposition and particle size distribution. Simulations of dynamic airflow and particle deposition during an inhalation cycle are performed for different nasal cavity outlet pressure variations and different particle injections. The total particle deposition efficiency under dynamic flow is found to depend strongly on the dynamics of airflow as well as the type of particle injection.

Recent advances in carrier mediated nose-to-brain delivery of pharmaceutics

Graphical abstract Figure. No caption available. Abstract Central nervous system (CNS) disorders (e.g., multiple sclerosis, Alzheimer’s disease, etc.) represent a growing public health issue, primarily due to the increased life expectancy and the aging population. The treatment of such disorders is notably elaborate and requires the delivery of therapeutics to the brain in appropriate amounts to elicit a pharmacological response. However, despite the major advances both in neuroscience and drug delivery research, the administration of drugs to the CNS still remains elusive. It is commonly accepted that effectiveness‐related issues arise due to the inability of parenterally administered macromolecules to cross the Blood‐Brain Barrier (BBB) in order to access the CNS, thus impeding their successful delivery to brain tissues. As a result, the direct Nose‐to‐Brain delivery has emerged as a powerful strategy to circumvent the BBB and deliver drugs to the brain. The present review article attempts to highlight the different experimental and computational approaches pursued so far to attain and enhance the direct delivery of therapeutic agents to the brain and shed some light on the underlying mechanisms involved in the pathogenesis and treatment of neurological disorders.

A Process System Approach to Nose-to-Brain Delivery of Biopharmaceutics

Abstract A process systems approach towards the development and integration of computational models to describe the application, adhesion, spreading, and stability of a reacting hyaluronic acid gel onto the Olfactory mucous layer as well as the release of drug from particles dispersed in the hydrogel matrix, diffusion, and transfer through the mucous layer is described. The initial results from this systems approach reveal the connection between the physico-chemical processes which can lead to design limitations, e.g., gel extrusion time influences the extent of spreading on the mucous layer.