General provisions

The course can be part of the master programme in Pharmaceutical Modelling, or the Master of Science programme in Pharmacy.

Entry requirements

150 credits in biomedicine, pharmaceutical science, drug discovery and development, natural science, and/or technology. Prior studies should include 15 credits in chemistry. Proficiency in English equivalent to the Swedish upper secondary course English 6.

Learning outcomes

On completion of the course, the student should be able to:

• apply knowledge dealing with the Poisson-Boltzmann and Gouy-Chapman theories to understand electrostatic interactions in pharmaceutical and biological systems
• apply knowledge dealing with thermodynamic principles and models for the self-assembly of amphiphilic molecules
• apply knowledge dealing with models based on bending elasticity and spontaneous curvature to understand the formation of micelles, membranes and microemulsions
• account for assumptions and restrictions in different theories for macromolecules
• apply knowledge dealing with the thermodynamic driving forces that underlies swelling of polymer coils and gels, phase separation in polymer solutions and formation of complexes in systems of oppositely charged polyelectrolytes
• apply knowledge dealing with different transport mechanisms and their relevance for the release of drugs from different pharmaceutical formulations
• account for how the structure of materials influence the effective transport properties, in particular with respect to diffusion
• use molecular dynamics simulations as a tool for simulations of pharmaceutically relevant molecules, for example peptides
• analyse structural and dynamic properties of the simulated systems
• apply knowledge how different levels of coarse-graining are applicable in different circumstances.
• apply knowledge dealing with basic principles of the experimental techniques static and dynamic light scattering, small-angle x-ray and neutron scattering
• perform simple analysis of experimental light scattering and small-angle scattering data
• apply analytic methods to solve quantitative problems

Content

The course embraces studies of molecular physical-chemical models relevant for applications in pharmacy, pharmaceutics and drug delivery. An introduction to experimental scattering techniques is included to study different systems that are treated in the course. The course is divided into the following parts:

1) Theories for modelling electrostatic energies and interactions in pharmaceutical and biological systems. Poisson-Boltzmann and Gouy-Chapman theories for the electrostatic double-layer are treated. During the course, the theoretical models are applied to, among other things, self-assembly of ionic amphiphilic molecules and polyelectrolytes.

2) Self-assembly of amphiphilic molecules in pharmaceutical and biological systems. Basic molecular thermodynamic models are dealt with and applied to describe the formation of micelles, membranes and microemulsions. Molecular models based on bending elasticity and spontaneous curvature are used to understand the self-assembly process and to predict the size and geometrical shape of the aggregates. The models are applied to pharmaceutical relevant problems such as the self-assembly of bile salts, phospholipids and amphiphilic drugs, and solubilisation of water-insoluble drugs.

3) Macromolecules, biopolymers and gels in pharmaceutical and biological systems. The behaviour of macromolecules and gels are treated from a theoretical perspective with focus on properties relevant for formulation and administration of drugs. Molecular thermodynamic models are dealt with to describe single polymer coils in solution, the phase behaviour of polymer solutions, the elasticity of polymer networks as well as polyelectrolyte solutions. The models are applied to show how the results can be used to model and analyse specific systems and problems such as compaction of DNA, gel swelling, formation of complexes in mixtures of oppositely charged polyelectrolytes as well as encapsulation of protein drugs and amphiphilic drugs in microgels.

4) Transport and release of drugs. Transport processes relevant for the release of drugs from different pharmaceutical formulations are treated, including basic theory for the mathematical description of transport mechanisms such as diffusion, convection and electric. Effective transport properties for disordered materials are treated (pore networks, effective medium theory and percolation) with focus on diffusion, as well as approximate methods for solving simple problems of drug release.

5) Methods and applications of classical molecular dynamics simulations for pharmaceutically relevant systems. Emphasis will be on the use of simulations for studying the behaviour of biological peptide drugs, and how they interact with other constituents of the small intestine, such as bile salts and phospholipids present as, for instance, micelles and membranes.

6) Introduction to scattering techniques for structural analysis of molecular drug formulations, drug delivery and biological systems. This part includes static and dynamic light scattering as well as small-angle x-ray and neutron scattering (SAXS and SANS) to experimentally determine molecular nanostructures in pharmaceutical and biological systems.

In addition to lectures, the course includes one computer exercise in molecular simulation techniques and an experimental exercise in light scattering and small-angle scattering.

Instruction

Teaching is in the form of lectures as well as experimental and computer exercises.

Compulsory parts: Experimental and computer exercises.

Assessment

Passed course demands a passed written individual examination (6 hp) and passed compulsory exercises (1.5 hp). If there are special reasons for doing so, an examiner may make an exception from the method of assessment indicated and allow a student to be assessed by another method. An example of special reasons might be a certificate regarding special pedagogical support from the University's disability coordinator