Chapter 6

### LEARNING OBJECTIVES

After completing this chapter, the reader should be able to:

• ► Appreciate the role of thermodynamics and kinetics in the transport of molecules across a region.

• ► Understand the different forms of transport processes in biological and pharmaceutical systems.

• ► Distinguish between passive, facilitated, and active transport of solute molecules.

• ► Understand solvent transport and the process of osmosis.

• ► Describe the different membrane systems that are relevant to pharmacy.

• ► Identify the different terms and units of Fick's law of diffusion.

• ► Understand the differences between zero- and first-order diffusional release in pharmaceutical systems.

• ► Appreciate the role of the lag-time effect and burst effect on the diffusion of drugs from a delivery device.

• ► Appreciate the significance of diffusion in biological and pharmaceutical processes.

• ► Appreciate the role of osmosis in biological and pharmaceutical processes.

### INTRODUCTION

Mass transport refers to the movement of molecules from one region to another as a result of a specific driving force. Two fundamental physical concepts are involved in the transport of substances across a region: the principles of thermodynamics and kinetics.1

Thermodynamics involves energy change in a process that determines directionality. According to thermodynamic principles, systems tend to go toward a decrease in free energy. This means that a particular reaction will occur in the direction stated only if the free energy of the product is lower than the free energy of the reactants. When a patient takes a tablet or capsule formulation orally, the drug dissolves in the stomach and the majority of the absorption of the solution occurs in the upper intestine (duodenum, jejunum). From a thermodynamic point of view, drug absorption from the gastrointestinal tract into the bloodstream occurs because the free energy of the molecules in the gastrointestinal tract is much higher than the free energy in the bloodstream. Free energy in this case is related to the concentration of the molecules at the two sites. The concentration of the drug in the gastrointestinal tract is much higher than that in the bloodstream. According to thermodynamic principles, movement of drug from the gastrointestinal lumen to the bloodstream decreases this imbalance of free energy in the two compartments of the body. If the drug is transported into the body, the free energy of the molecules decreases (concentration decreases) and the free energy of the molecules in the bloodstream increases (concentration increases). There is a point where the two free energies are equal and the change in free energy is zero. This is the point of equilibrium that all reversible processes strive to achieve. At the point of equilibrium, the movement of drug molecules from the gastrointestinal tract into the bloodstream will stop. In all transport systems, the free energy change has to be favorable for the process to occur.

Kinetics is based on the effect of time on a process or reaction (see ...

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