Pharmaceutical Analytical Chemistry I - Lecture 1 - Introduction to Chemical Kinetics - PDF

# Pharm. D ## Pharmaceutical Analytical Chemistry I - PC_101 ### Lecture 1 - Introduction to Chemical Kinetics By: Assistant Prof. Ashraf Mohamed Taha www.su.edu.eg ## Content 1. Introduction to Chemical Kinetics 2. Importance of Chemical Kinetics in the Pharmaceutical field 3. Reaction Rates ## 1...

# Pharm. D ## Pharmaceutical Analytical Chemistry I - PC_101 ### Lecture 1 - Introduction to Chemical Kinetics By: Assistant Prof. Ashraf Mohamed Taha www.su.edu.eg ## Content 1. Introduction to Chemical Kinetics 2. Importance of Chemical Kinetics in the Pharmaceutical field 3. Reaction Rates ## 1. Introduction to Chemical Kinetics A very important characteristic of a reaction is its spontaneity. **Spontaneity refers** to the inherent tendency for the process to occur; however, it implies nothing about speed. **Spontaneous does** not mean fast. There are many **spontaneous reactions** that are so slow that no apparent reaction occurs over a period of weeks or years at normal temperatures. For example, there is a strong inherent tendency for gaseous hydrogen and oxygen to combine, that is $2H_2(g) + O_2(g) -> 2H_2O(l)$ but in fact, the two gases can coexist indefinitely at 25°C. **Chemical kinetics** is the branch of physical chemistry that is concerned with understanding the rates of chemical reactions. It is to be contrasted with **thermodynamics**, which deals with the direction in which a process occurs but tells nothing about its rate. **Thermodynamics** is time's arrow, while chemical kinetics is time's clock. **Chemical kinetics** relates to many aspects of cosmology, geology, biology, engineering, and even psychology and thus has far-reaching implications. The principles of **chemical kinetics apply** to purely physical processes as well as to chemical reactions. - Chemical reactions take time to occur. Some reactions, such as the rusting of iron, occur relatively slowly, requiring days, months, or years to complete. - Others, such as the decomposition of sodium azide, the reaction used to inflate automobile air bags, occur so quickly they are difficult to measure. - As pharmacist, we need to be concerned about the speed of chemical reactions as well as the products of those reactions. **Factors affecting speed of reaction:** Concentration of reactants, Pressure (for gases only), particle size, catalyst, temperature, light The importance of the studying the rates of chemical reactions: - One reason for studying the rates of reactions is the practical importance of being able to predict how quickly a reaction mixture approaches equilibrium. - The rate might depend on variables under our control, such as the temperature and the presence of a catalyst, and we might be able to optimize it by the appropriate choice of conditions. - Another reason is that the study of reaction rates leads to an understanding of the mechanism of a reaction, its analysis into a sequence of elementary steps. The following examples illustrate the importance of the rates of chemical reactions and how to be useful, reactions must occur at a reasonable rate: - **Milk** is stored in a refrigerator to slow down the chemical reactions that **cause it to spoil**. - **Rocket fuel** is designed to give a rapid release of gaseous **products and energy** to provide a **rocket** maximum thrust. - **Current strategies** to reduce the **rate of deterioration** of the ozone layer try to deprive the **ozone-consuming reaction cycle** of key intermediates that come from **chlorofluorocarbons (CFCs)**. - **Analyzing the rates of biochemical reactions**, we may discover how they take place in an **organism and contribute to the activity of a cell**. - **Enzyme kinetics**, the study of the **effect of enzymes on the rates of reactions**, is also an important window on how these **macromolecules work**. To fully understand **chemical reactions**, we need to combine the predictions of **thermodynamics** with studies of the factors that influence the rates of chemical reactions. These factors fall under the general heading of **chemical kinetics** (from a Greek stem meaning "to move"), which is the subject of this chapter. **Chemical kinetics plays** an important role in processes as diverse as the production of **chemicals on an industrial scale** and the decay of radioactive isotopes **used in medicine**. **Chemical kinetics** is also useful in **providing information** about how reactions occur - the order in which chemical bonds are broken and formed during a reaction. To understand how reactions happen, we must examine the **reaction rates and the factors** that influence them. **Experimental information** on the rate of a given reaction provides important evidence that **helps us formulate a reaction mechanism**, which is a **step-by-step, molecular-level view** of the pathway from reactants to products. ## 2. Importance of Chemical Kinetics in the Pharmaceutical field The **study of chemical kinetics is essential** in the pharmaceutical industry. - Helps to understand the **rate of chemical reactions and the factors** that affect them. - Also, the study of **chemical kinetics** is very crucial as it plays a significant role in **drug stability**. ### 2.1. Drug Stability and Shelf Life: - **Chemical kinetics** is fundamental in **predicting the stability of drugs** over time. The **rate at which drugs degrade**, undergo oxidation, hydrolysis, or other **chemical transformations is governed by kinetic principles**. - Understanding these processes helps in determining the shelf life of drugs and establishing **appropriate storage conditions** (temperature, humidity, etc.) to minimize degradation and **ensure efficacy** until the product reaches the patient. **Factors affecting rate of drug degradation:** Temperature, pH, light intensity, excipients (type, dielectric constant, and ionic strength), solvents. ### 2.2. Bioavailability - **Chemical kinetics** also plays a vital role in the study of **drug absorption and distribution** in the body. The rate of drug metabolism and elimination determines the drug's bioavailability,.... - ...which refers to the fraction of the **administered drug** that reaches the bloodstream in an active form. - Understanding these kinetic properties allows for better design of drug dosage forms that ensure the **drug reaches its target in optimal concentrations**. **Drug degradation in human intestinal fluids:** - GI tract - Ester-based drugs - Intestinal fluids ### 2.3. Manufacturing Process Optimization - **Chemical kinetics** is crucial in the **optimization of pharmaceutical manufacturing processes**. For example, it helps in determining the ideal conditions for reactions **involved in the synthesis of active pharmaceutical ingredients (APIs)**. - By understanding **reaction rates and mechanisms**, manufacturers can scale up production from laboratory to industrial scale while **maintaining product quality and minimizing waste**. Kinetic models are used to **predict outcomes** in large-scale production, ensuring efficient use of raw materials and reducing costs. ## 3. Reaction Rates The **speed of an event** is defined as the change that occurs in a given time interval, which means that whenever we talk about speed, we necessarily bring in the notion of time. For example, the speed of a car is expressed as the change in the car's position over a certain time interval. Similarly, the **speed of a chemical reaction - its reaction rate** - is the change in the **concentration of reactants or products** per unit of time. The units for **reaction rate** are usually **molarity per second (M/S)** - that is, the change in concentration **measured in molarity** divided by a time interval **measured in seconds**. **Definition of rate of reaction:** - The rate of a chemical reaction is the change in concentration of reactants or products per unit time. **Rate of reaction = increase in product concentration / change in time** **Rate of reaction = decrease in reactant concentration / change in time** Let's consider the hypothetical reaction A -> B, depicted in Figure 1. Each red sphere represents 0.01 mol of A, each blue sphere represents 0.01 mol of B, and the container has a volume of 1.00 L. - At the beginning of the reaction, there is 1.00 Mol A, so the concentration is 1.00 mol/L = 1.00 M. After 20 s, the concentration of A has fallen to 0.54 M and the concentration of B has risen to 0.46 M. - The sum of the concentrations is still 1.00 M because 1 mol of B is produced for each mole of A that reacts. After 40 s, the concentration of A is 0.30 M and that of B is 0.70 M. - The rate of this reaction can be expressed either as the rate of disappearance of reactant A or as the rate of appearance of product B. - The average rate of appearance of B over a particular time interval is given by the change in concentration of B divided by the change in time: **Average rate of appearance of B = change in concentration of B / change in time** **= [B] at t2 - [B] at t1 / t2 - t1** **= Δ[B] / Δt** - We use brackets around a chemical formula, as in [B], to indicate molarity. The Greek letter delta, Δ, is read "change in" and is always equal to a final value minus an initial value. - The average rate of appearance of B over the 20 s interval from the beginning of the reaction (t1 = 0 to t2 = 20 s) is: **Average rate = 0.46 M - 0.00 M / 20 s - 0 s** **= 2.3 x 10-2 M/s** - We could equally well express the reaction rate in terms of the reactant, A. In this case, we would be describing the rate of disappearance of A, which we express as: **Average rate of disappearance of A = - change in concentration of A / change in time** **= - Δ[A] / Δt** - Notice the minus sign in this equation, which we use to indicate that the concentration of A decreases. By convention, rates are always expressed as positive quantities. Because [A] decreases, Δ[A] is a negative number. - The minus sign we put in the equation converts the negative Δ[A] to a positive rate of disappearance. Because one molecule of A is consumed for every molecule of B that forms, the average rate of disappearance of A equals the average rate of appearance of B: **Average rate = - Δ[A] / Δt** **= -(0.54 M - 1.00 M) / 20 s - 0 s** **= 2.3 x 10-2 M/s** ### Sample Exercise 1: From the data in Figure 1, calculate the average rate at which A disappears over the time interval from 20 s to 40 s. ### Solution: Analyze: We are given the concentration of A at 20 s (0.54 M) and at 40 s (0.30 M) and asked to calculate the average rate of reaction over this time interval. Solve: **Average rate = - Δ[A] / Δt** **= -(0.30 M - 0.54 M) / 40 s - 20 s** **= 1.2 x 10-2 M/s** **Note:** The provided text is a lecture on chemical kinetics and its importance in the pharmaceutical field. It explains how the rates of chemical reactions guide drug stability, bioavailability, and manufacturing processes. The document also features examples and sample exercises.