Chapter 11

### LEARNING OBJECTIVES

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

• ► Describe the impact of reaction kinetics in the context of drug formulations.

• ► Describe the impact of reaction kinetics in the context of pharmacotherapy.

• ► Indicate the units of the reaction rate constants for zero-order and first-order reactions.

• ► For zero-order and first-order reactions, define the rate equations, the integrated rate equations, and the mathematical expressions for half-life (t½) and shelf life (t90).

• ► Describe the concept of pseudo reaction order.

• ► From tabulated reaction kinetic data, create a graph of drug concentration versus time and use the graph to determine the rate constants, half-life and shelf-life values, and apparent reaction order.

• ► Calculate the shelf life (t90) of drugs from mathematical equations and from graphical representations of reaction kinetic data.

• ► Describe the influence of temperature on reaction rates.

• ► Estimate the shelf life (t90) and expiration time of drugs at storage temperature by analyzing accelerated stability-testing data.

• ► Describe the impact of pH and solvent on the catalysis of reactions.

• ► Evaluate the log k versus pH profile of drugs and identify the pH at which a drug is most stable.

• ► Apply first-order reaction rate concepts to complex reactions such as reversible, parallel, and consecutive (series) reactions.

• ► Relate reaction kinetic principles to pharmacokinetics.

### INTRODUCTION

Pharmacists encounter the impact of the chemical degradation of pharmaceuticals in the course of their everyday activities. Proper storage of drug products, providing beyond use dates for prescriptions, and the preparation and storage of sterile products are some examples of common scenarios that are dependent on the knowledge of the chemical kinetics of pharmaceuticals. Therefore, for both safety and economic reasons, it is advantageous for pharmacists to be knowledgeable about the topic of chemical kinetics. The basis for understanding chemical kinetics is the knowledge of the processes involved in chemical degradation and the time dependence on chemical degradation. Understanding the mathematical principles describing the degradation processes is necessary to make sound professional decisions. Fortunately, the primary mathematics are common to other pharmacy topics, particularly pharmacokinetics and biopharmaceutics. In this chapter, we investigate the chemical kinetics of pharmaceuticals focusing on first-order and zero-order reactions, which are the most commonly encountered categories of pharmaceutical degradation reactions.

To ensure that the patient receives the correct dose of a drug, whatever form it is carried in (liquid medicines, tablets, gel caps, etc.), the rate of degradation of a drug must be known. The length of time a drug remains stable is determined by inherent and external factors. Inherently, a drug may be changed or decomposed at a molecular level by the changing of energy and the breaking of molecular bonds. This can result from the temperature at which a drug is stored or by other chemicals with which an active drug ...

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