Lecture 9 Kinetics, Reaction Rates and Drug Stability PDF

1 Lecture 9 Kinetics, Reaction Rates and Drug Stability  2 Introduction ❑ Kinetics comes form the Greek word kinesis meaning movement. ❑ Reaction kinetics is the “study of rate of chem...

1 Lecture 9 Kinetics, Reaction Rates and Drug Stability  2 Introduction ❑ Kinetics comes form the Greek word kinesis meaning movement. ❑ Reaction kinetics is the “study of rate of chemical change and the way in which this rate is influenced by the conditions of concentration of the reactants, products, and other chemical species which may be present, and by factors such as solvent, pressure , and temperature”. ❑ Is study of the rate at which processes or changes occur Importance of studying kinetics 3 ❑ To determine half life ❑ To determine shelf life (t0.9) ❑ Selection of proper storage condition ▪ Temperature and humidity ▪ advising patient on storage conditions ❑ To determine incompatibilities ❑ Dissolution determinations ❑ To study ADME Processes in pharmacokinetics  Rate and order of reactions 4 Rate of reaction ❑Is the velocity or speed of a reaction with which a reactant(s) undergo a change. ❑Can be measured by measuring the change in the conc. of a reactant or product in a particular period of time ❑Given by;rate = ±dc/dt  Rate and order of reactions 5 Order of reaction ❑Refers to the way in which the concentration of the reactant (s) influence the rate of a chemical rxn. ❑According to law of mass action, the rate of a reaction is proportional to the product of the molar concentration of reactants each raised to power equal to the number of molecules undergoing reaction.  6 Order of reaction = sum of exponents Order of A = a and B = b Then overall order = a + b K is the rate constant or specific rate constant 7  8 zero order reaction The rate of a reaction is not dependent on the concentration of the reacting species where dC is the change in concentration, dt change in time t minus sign indicates that the concentration is decreasing 9 When this linear equation is plotted with conc. on the vertical axis and time on the horizontal axis, the slop 10 of the line give –K  11 Half life of zero order reaction The half life is the time required for 50% of the material to disappear it is the time at which Co is decreased to 1/2Co Let C = Co /2 and t1/2 = t substituting this into eq. 2, yields C = Co– k t t1/2 = Co / 2K Shelf life of a zero order reaction 12 The shelf life is the time required for 10% of the material to disappear it is the time at which Co has decreased to 90% of its original concentration Let C = 0.9Co and t= t0.9 substitute in eq. 2; C = Co–k t T 90% = t0.9 = 0.1 co / k 13  Suspensions. Apparent Zero-Order Kinetics 14 Suspensions are another case of zero-order kinetics, in which the concentration in solution depends on the drug's solubility. As the drug decomposes in solution, more drug is released from the suspended particles so that the concentration remains constant. This concentration is, of course, the drug's equilibrium solubility in a particular solvent at a particular temperature. The important point is that the amount of drug in solution remains constant despite its decomposition with time. The reservoir of solid drug in suspension is responsible for this constancy. 15 16 17 18  19 C  First-order reaction 20 The rate of the reaction is directly proportional to the first power of a concentration of single reactant. The reaction can be written as Where C is the concentration of the reactant A remaining undecomposed at time t and K is the first-order rate constant 21 22 23 24  25 the half life and shelf life of first order reaction is a constant independent of the concentration 26 Apparent or Pseudo-Order 27 “Apparent” or “pseudo”-order describes a situation where one of the reactants is present in large excess or does not Usually, the overall reaction and can be held constant. For example, many hydrolysis decomposition reactions of drug molecules are second order. Usually, the amount of water present is in excess of what is needed for the reaction to proceed. In other words, the concentration of water is essentially constant throughout the reaction. In this case, the second-order reaction behaves like a first-order reaction and is called an apparent or pseudo–first-order reaction. 28 29 Methods for determining the order of reaction 30 1. Substitution method 2. Graphical method 3. Half life method  31 1.Substitution method: The data obtained from a kinetic experiment is substituted in the relevant integrated equation. The equation that yields a fairly constant value of K within the limits experimental variation indicates the order of the reaction  32 2. Graphical method: The data obtained from a kinetic experiment is plotted in the relevant form to determine the order of a particular reaction Zero-order if straight line is obtained by plotting the concentration a against time t First-order if a plot of log c versus t yields a straight line, the reaction is first order.  33 3. Half life method: A general expression for the determination of the half life of a reaction can be given as: If the two reactions are run at different initial concentrations, a1 and a2, the respective half-lives t1/2(1) and t1/2(2) are related as follows:  Or in logarithmic form 34 ❑The half-lives are determined graphically by plotting c versus t at two different initial concentrations and reading the time at 1/2a1 and 1/2a2 ❑The values for the half-lives and the initial concentrations are then substituted into the above equation. Q. 1. The kinetics of decomposition of a drug in aqueous solution were studied using a series of solutions of different 35 initial drug concentrations, C0. For each solution the time taken for half the drug to decompose (that is, t0.5) was determined with the following results: Determine the order of reaction. 87.17 log( ) 𝑛= 240.1 +1 =2 log(1.698/4.625) 36  37 The effect of temperature on reaction rate is given by the Arrhenius equation  38 0°C + 273.15 = 273.15K 39  40 Q. 1. The first-order rate constant for the hydrolysis of sulfacetamide at 120°C is 9x10-6 S-1 and the activation energy is 94 kJ mol-1. Calculate the rate constant at 25°C. Prediction of shelf life 41 42