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# kinetics and drug stability

for jntuk syllubus
Published on: Mar 3, 2016
Published in: Education

#### Transcripts - kinetics and drug stability

• 1. 2/7/2016 vignan pharmacy college 1
• 2. CONTENTS • Introduction • Rates and order of reaction • Method for determining the order of reaction • Complex reaction • Factor affecting rate of reaction • kinetics of drugs decompositions 2/7/2016 2vignan pharmacy college
• 3.  Drugs stability is defined as the pharmaceutical dosages form to maintain the physical, chemical, therapeutic and microbial properties during the time of storage and uses by the patient.  Stability is defined as the capacity of a drugs substance to remain within the established specification to maintain its identity, strength, quality and purity throughout the retest or expiration during period. Definition kinetics & Drug stability 2/7/2016 vignan pharmacy college 3
• 4. Chemical kinetics is the study of rate of chemical changes taking place during chemical reaction. As applied to pharmaceutical formulation , this include a study of physical and chemical changes in drugs and dosage form, factor influencing the rate of these chemical reaction, accelerated stability testing and prediction of shelf life. 2/7/2016 vignan pharmacy college 4
• 5. RATES AND ORDER OF REACTION  The velocity with which a reaction or a process occurs is called as its rate, concentration of drugs influences the rate of reaction or process is called as the order of reaction or order of process. Consider the following chemical reaction Drug A Drug B 2/7/2016 5vignan pharmacy college
• 6.  The rate of forward reaction is expressed as : -dA/dt -ve sign = concentration of drugs A decreases with time.  As the reaction proceeds, the concentration of the drugs B increases and the rate of reaction can also be expressed as: dB/dt  Experimentally, the rate of reaction is determined by measuring the decrease in concentration of drugs A with time. 2/7/2016 vignan pharmacy college 6
• 7.  If c is the concentration of drug A, the rate of decrease in c of drug A as it is changed to B can be described by expression as function of time t. dC/dt = -kc Where, k= rate constant n=order of reaction If, n= 0 (zero order process) n= 1 (first order process)2/7/2016 vignan pharmacy college 7
• 8.  The order of a reaction determines the way in which the concentration of a reactant or reactants influences the rate of a chemical reaction. Molecularity of Reaction  The molecularity of a reaction refers to the numbers of molecules, atoms, or ions reacting in a elementary process to give the reactants.  If only one type of molecules undergoes a change in to yield the product , the product is said to be unimolecular. 2/7/2016 8vignan pharmacy college
• 9.  If two molecules undergoes to change yield the product, the reaction is said to be bimolecular.  Reaction that involves more than one steps ( complex reaction) may have different molecularity and order of reaction.  The three commonly encountered rate process: Zero order reaction First order reaction Mixed order reaction 2/7/2016 9vignan pharmacy college
• 10. Zero-order kinetics o Its is also called as constant rate process. o The reaction is said to be zero-order reaction , if the rate of reaction is independent of the concentration i.e. the rate of reaction can not be increased further by increasing the concentration of reactants. dc/dt= -KoCo = -Ko equation.....1 Where Ko = zero-order rate constant (in mg/min) 2/7/2016 10vignan pharmacy college
• 11. Rearrangement of equation 1 yields: dc= -Ko dt equation..........2 Integration of equation 2 gives: C - Co = - k0 t where Co = concentration of drug at t = 0, and C = concentration of drug yet to undergo reaction at time t. 2/7/2016 vignan pharmacy college 11
• 12. Fig. 1. Graphs of zero-order kinetics 2/7/2016 12vignan pharmacy college
• 13. First-order kinetics  Whose rate is directly proportional to the concentration of the of drugs undergoing reaction i.e. greater the concentration , faster the reaction. First-order process is said to follow linear kinetics CK dt dC  Where K = first-order rate constant (per hour) 2/7/2016 vignan pharmacy college 13
• 14. Fig. 2: Graph of first-order kinetics showing linear relationship between rate of reaction and concentration of drug 2/7/2016 vignan pharmacy college 14
• 15. Mixed order kinetics In some instances, the kinetics of a pharmacokinetic process changes from predominantly first-order to predominantly zero-order with increasing dose or chronic medication. A mixture of both first-order and zero-order kinetics is observed in such cases and therefore the process is said to follow mixed-order kinetics.  Since deviations from an originally linear pharmacokinetic profile are observed, the rate process of such a drug is called as nonlinear kinetics. 2/7/2016 vignan pharmacy college 15
• 16. Mixed order kinetics is also termed as dose-dependent kinetics as it is observed at increased or multiple doses of some drugs. Nonlinearities in pharmacokinetics have been observed in –  Drug absorption (e.g. vitamin C)  Drug distribution (e.g. naproxen), and  Drug elimination (e.g. riboflavin). The kinetics of such capacity-limited processes can be described by the Michaelis-Menten kinetics. 2/7/2016 16vignan pharmacy college
• 17. Complex reaction Many chemical reaction encountered in the pharmaceutical field are not simple reaction of the zero, first, second or third order but consists of a combination of two or more reaction . such reaction is known as complex reaction. Complex reaction may be classified as: • Reversible reaction • Parallel reaction • Consecutive or series reaction 2/7/2016 vignan pharmacy college 17
• 18. Factor affecting rate of reaction •Temperature •Light •Solvent •Ionic strength •Dielectric constant of solvents •Catalysis •Surfactants 2/7/2016 vignan pharmacy college 18
• 19. Kinetics of drugs decomposition  A drugs in suspension follows apparent zero order kinetics in which the concentration of the drugs in the solution remains constant with time.  When the drugs in the solution degrades or lost by any means new drugs molecules from the suspended solid particles dissolved in the solution to keep the concentration constant at the equilibrium solubility. That is the solid suspended particles act as reservoir of drugs. 2/7/2016 19vignan pharmacy college
• 20.  Acid catalysed hydrolysis of the digoxin follows pseudo first order reaction kinetics , here the concentration of H+ remains constant . Therefore the rate slowly depends on the concentration of digoxin.  Hydrolysis of chlorbutanol in presence of sodium hydroxide follows second order reaction. 2/7/2016 vignan pharmacy college 20
• 21. Strategy of stability testing  Strategy is important for the stability testing of any dugs to maintain their shelf life . To maintain the shelf life of drugs the ICH and WHO guideline for stability testing should be followed.  Protection against hydrolysis  Protection against oxidation 2/7/2016 21vignan pharmacy college
• 22. Accelerated stability analysis Accelerated stability analysis is design to predict stability and hence shelf life of formulation under normal and recommended storage condition by carrying out the study under accelerated condition of temperature, moisture and light. Prediction of shelf life  Shelf life is the time period during which the dosages form is supposed to retain its original quantity.  The prediction is based on the arrhenius equation .2/7/2016 vignan pharmacy college 22
• 23. Stability of solid dosages form  The decomposition of drugs in solid dosages form is more complex than that occurring in the pure drugs.  The following are the effect of various factor on the stability in solid dosages form: Temperature Moisture Chemical interaction 2/7/2016 vignan pharmacy college 23
• 24. Types of stability studies Long term stability studies Accelerated stability studies Testing frequency Packaging and container 2/7/2016 vignan pharmacy college 24