1. The document discusses the stability of pharmaceutical products and factors that affect stability such as temperature, moisture, light, and packaging.
2. It covers different types of stability including chemical, physical, and microbiological stability. Regulatory requirements for stability studies and guidelines from organizations like ICH are also reviewed.
3. The major pathways for drug degradation are described as physical degradation, chemical degradation through oxidation, hydrolysis, and other reactions. Methods to protect against these degradation pathways are summarized.
This document discusses drug stability and stability testing. It defines stability as the extent to which a product retains its properties over time. Stability testing is necessary to determine shelf life, recommended storage conditions, and ensure safety. There are various types of stability including chemical, physical, and microbiological. Testing is conducted for different formulations like tablets, capsules, emulsions, and involves evaluating attributes like appearance, assay, degradation products, and more. Guidelines provided by ICH help harmonize stability testing globally.
1. Drug stability testing involves conducting studies under various temperature, humidity and light conditions to determine a drug's shelf life and optimal storage requirements.
2. The ICH Q1A guideline provides the standard process for stability testing new drug substances and products to obtain registration. It defines testing stages, storage conditions and frequencies to evaluate how quality varies over time.
3. Stability testing helps establish expiration dates and provides evidence for appropriate packaging and labeling to ensure drug quality through a product's shelf life.
stability tests for pharmaceutical productsalaaalfayez
These documents provide guidance on stability testing and evaluation for pharmaceutical products. The purpose of stability testing is to provide evidence on how a drug product's quality varies over time under various environmental conditions. Key aspects addressed include testing the drug substance and finished product under different timepoints and storage conditions to establish or extend a product's shelf life. The documents outline best practices for conducting long-term, accelerated, and intermediate stability studies to evaluate the impact of factors like temperature, humidity, and light on a product's physical, chemical, biological, and microbiological properties over time.
This document discusses stability studies and drug kinetics. It defines stability as how a product maintains its quality over time. Stability testing is used to determine shelf life, recommended storage conditions, and container suitability. Kinetics deals with the rates of chemical reactions and processes. The order of a reaction determines how concentration influences the reaction rate. Common orders seen in drug degradation are zero order (rate is constant), first order (rate depends on concentration of one reactant), and second order (rate depends on concentrations of two reactants). Understanding reaction kinetics helps predict degradation over time and ensure drug quality.
The document provides an overview of stability testing during product development. It discusses the importance of stability testing to ensure product quality and safety over the shelf life. Various methods of stability testing are described, including real-time, accelerated, and retained sample testing. Guidelines for stability testing from ICH, WHO, and other agencies are also covered. The document outlines the key aspects of a stability testing protocol, including batches, containers, storage conditions, sampling plan, test parameters, and acceptance criteria. It provides details on conducting, recording, and presenting stability testing data.
Drug stability refers to a drug substance or product remaining within established specifications over time. The stability of a product is expressed as its shelf life or expiry period. Stability testing involves multiple stages from early stress testing to ongoing long-term testing as required by regulatory bodies. Stability is affected by various factors related to the drug, formulation, and environment. Reduced stability study designs like bracketing and matrixing allow testing of representative samples and are acceptable with proper scientific justification.
Stability testing and shelf life estimationManish sharma
Drug stability refers to the extent to which a pharmaceutical product retains its quality attributes, such as concentration of active ingredients, over time. Stability testing is necessary to determine a drug's shelf life and recommended storage conditions. It involves evaluating a drug's chemical, physical, and microbial properties under different temperatures and humidity levels over time. The Arrhenius equation can be used to predict a drug's stability at normal temperatures based on its degradation rates observed during accelerated stability testing at elevated temperatures. International guidelines provide recommendations for long-term and accelerated stability study protocols and minimum data requirements for drug substances and products to ensure quality, safety and efficacy over a product's shelf life.
Bracketing and Matrixing Methods for Stability analysisSarath Chandra
This document discusses bracketing and matrixing designs for stability testing of new drug substances and products according to ICH Q1D guidelines. Bracketing design involves testing only the extremes of design factors like strength or container size, assuming stability of intermediates is represented by extremes. Matrixing design involves testing selected combinations of factors at each time point rather than all combinations at all time points. Both designs provide reduced testing compared to full design testing all samples at all time points, but require justification and carry potential risks of underestimating shelf life if variability is high.
This document discusses drug stability and stability testing. It defines stability as the extent to which a product retains its properties over time. Stability testing is necessary to determine shelf life, recommended storage conditions, and ensure safety. There are various types of stability including chemical, physical, and microbiological. Testing is conducted for different formulations like tablets, capsules, emulsions, and involves evaluating attributes like appearance, assay, degradation products, and more. Guidelines provided by ICH help harmonize stability testing globally.
1. Drug stability testing involves conducting studies under various temperature, humidity and light conditions to determine a drug's shelf life and optimal storage requirements.
2. The ICH Q1A guideline provides the standard process for stability testing new drug substances and products to obtain registration. It defines testing stages, storage conditions and frequencies to evaluate how quality varies over time.
3. Stability testing helps establish expiration dates and provides evidence for appropriate packaging and labeling to ensure drug quality through a product's shelf life.
stability tests for pharmaceutical productsalaaalfayez
These documents provide guidance on stability testing and evaluation for pharmaceutical products. The purpose of stability testing is to provide evidence on how a drug product's quality varies over time under various environmental conditions. Key aspects addressed include testing the drug substance and finished product under different timepoints and storage conditions to establish or extend a product's shelf life. The documents outline best practices for conducting long-term, accelerated, and intermediate stability studies to evaluate the impact of factors like temperature, humidity, and light on a product's physical, chemical, biological, and microbiological properties over time.
This document discusses stability studies and drug kinetics. It defines stability as how a product maintains its quality over time. Stability testing is used to determine shelf life, recommended storage conditions, and container suitability. Kinetics deals with the rates of chemical reactions and processes. The order of a reaction determines how concentration influences the reaction rate. Common orders seen in drug degradation are zero order (rate is constant), first order (rate depends on concentration of one reactant), and second order (rate depends on concentrations of two reactants). Understanding reaction kinetics helps predict degradation over time and ensure drug quality.
The document provides an overview of stability testing during product development. It discusses the importance of stability testing to ensure product quality and safety over the shelf life. Various methods of stability testing are described, including real-time, accelerated, and retained sample testing. Guidelines for stability testing from ICH, WHO, and other agencies are also covered. The document outlines the key aspects of a stability testing protocol, including batches, containers, storage conditions, sampling plan, test parameters, and acceptance criteria. It provides details on conducting, recording, and presenting stability testing data.
Drug stability refers to a drug substance or product remaining within established specifications over time. The stability of a product is expressed as its shelf life or expiry period. Stability testing involves multiple stages from early stress testing to ongoing long-term testing as required by regulatory bodies. Stability is affected by various factors related to the drug, formulation, and environment. Reduced stability study designs like bracketing and matrixing allow testing of representative samples and are acceptable with proper scientific justification.
Stability testing and shelf life estimationManish sharma
Drug stability refers to the extent to which a pharmaceutical product retains its quality attributes, such as concentration of active ingredients, over time. Stability testing is necessary to determine a drug's shelf life and recommended storage conditions. It involves evaluating a drug's chemical, physical, and microbial properties under different temperatures and humidity levels over time. The Arrhenius equation can be used to predict a drug's stability at normal temperatures based on its degradation rates observed during accelerated stability testing at elevated temperatures. International guidelines provide recommendations for long-term and accelerated stability study protocols and minimum data requirements for drug substances and products to ensure quality, safety and efficacy over a product's shelf life.
Bracketing and Matrixing Methods for Stability analysisSarath Chandra
This document discusses bracketing and matrixing designs for stability testing of new drug substances and products according to ICH Q1D guidelines. Bracketing design involves testing only the extremes of design factors like strength or container size, assuming stability of intermediates is represented by extremes. Matrixing design involves testing selected combinations of factors at each time point rather than all combinations at all time points. Both designs provide reduced testing compared to full design testing all samples at all time points, but require justification and carry potential risks of underestimating shelf life if variability is high.
The document discusses the Master Formula Record (MFR), which contains all information about the manufacturing process for a pharmaceutical product. It is prepared by the research and development team and used as a reference standard for preparing batch manufacturing records. The MFR includes details like product name, ingredients, batch size, manufacturing process steps, packaging process, and expected yields. It provides standardized instructions for consistently producing batches of a product.
Accelerated stability testing is used to predict the shelf life of pharmaceutical formulations by subjecting them to elevated temperatures and humidity to accelerate any degradation. The key steps involve conducting studies at different temperatures, determining the reaction order, calculating rate constants (k) at each temperature, determining the energy of activation using the Arrhenius equation, and extrapolating to room temperature to estimate shelf life. Limitations include changes in degradation mechanism or order at higher temperatures that limit the accuracy of shelf life predictions.
This document discusses drug stability and factors that affect it. It defines drug stability as a drug product remaining within established specifications for identity, strength, quality and purity. Factors like temperature, humidity, light and microbial contamination can cause drug degradation through chemical, physical and biological processes like hydrolysis, oxidation and photolysis. The document outlines various packaging materials and how they can impact stability. It also describes different types of stability studies conducted, including long-term real-time testing and accelerated methods like elevated temperature to evaluate products' shelf lives under normal conditions.
This document discusses guidelines from the International Council for Harmonisation (ICH) for stability testing of drug substances and products. It provides guidance on topics such as the need for harmonized stability testing, types of stability testing, selection of batches and storage conditions for testing, and evaluation of stability data. The guidelines aim to establish a systematic approach to stability testing to ensure quality, safety and efficacy over a product's shelf life and recommend conditions for testing drug substances intended for various storage conditions.
The International Conference on Harmonisation (ICH) was created in 1990 as a unique effort between regulators and industry from the EU, Japan, and US to harmonize technical requirements for pharmaceutical registration. ICH aims to ensure safety, efficacy, and quality of medicines while preventing duplicative trials and minimizing animal testing. Through guidelines developed via consensus building among members, ICH has harmonized requirements for drug development and approval processes. However, some concerns remain regarding inclusion of non-members in the decision making and implications for developing countries.
The document discusses guidelines for stability testing from the International Conference on Harmonisation (ICH). It provides an overview of several ICH guidelines related to stability testing of drug substances and products, including guidelines on photostability testing, new dosage forms, bracketing and matrixing designs, and evaluation of stability data. It also summarizes key aspects of conducting stability studies such as selecting representative batches, appropriate container closure systems, testing frequency and storage conditions, and evaluation of results. Stress testing is discussed as a way to validate analytical methods and identify potential degradants.
The International Council for Harmonisation (ICH) brings together regulatory authorities and the pharmaceutical industry to discuss technical requirements for drug registration. ICH has produced guidelines on quality, safety, efficacy, and multidisciplinary topics. The quality guidelines cover stability testing, analytical validation, impurities, Good Manufacturing Practice, and quality risk management. Together, the ICH guidelines aim to harmonize technical requirements across regions to provide efficient drug development and approval.
This document summarizes the ICH guideline for stability testing. The ICH provides guidance on stability testing to ensure drug quality over time under various environmental conditions. Key aspects covered include the objectives of stability testing, variables that affect stability, terminology, and ICH guidelines Q1A through Q1F which provide detailed recommendations on stability testing procedures, data evaluation, and submissions for registration.
Scale up and post approval changes(supac)bdvfgbdhg
The document discusses guidelines for post-approval changes to drug products, including changes to batch size, manufacturing sites and equipment, and composition. It outlines 3 levels of changes - minor, moderate, and major - and provides recommendations for documentation and regulatory filings required for each level of change. Major changes, such as a new manufacturing site or changes in the amount of active ingredients, require more extensive documentation including stability testing and possibly bioequivalence studies.
This document summarizes guidelines for stability testing of biotechnological and biological products. It discusses factors that can affect stability, including temperature, humidity, light and container materials. The guidelines specify conducting real-time stability studies at the proposed storage temperature and testing potency, purity and degradation over time. Manufacturers must propose a stability-indicating profile and validate methods to detect any changes to the identity, purity or potency of the product.
The document discusses the objectives and guidelines of the International Council for Harmonization (ICH) for stability testing of pharmaceutical products. It provides an overview of the key ICH guidelines for stability testing (Q1A-Q1F) and describes the principles of stability testing including establishing re-test periods and shelf lives. It also discusses the different types of stability testing, protocols, study designs like bracketing and matrixing, and key parameters for evaluation.
ICH Q10 provides a harmonized model for a pharmaceutical quality system throughout the lifecycle of a product. It describes a quality management system for the pharmaceutical industry. The objectives of the Q10 model are to achieve product realization, establish and maintain a state of control, and facilitate continual improvement. ICH Q10 covers pharmaceutical development, technology transfer, commercial manufacturing, and product discontinuation. It is intended to enhance existing good manufacturing practice requirements and be used together with them.
Accelerated stability testing exposes pharmaceutical products to elevated temperatures and humidity to rapidly determine their shelf life. Samples are stored at conditions like 40°C/75%RH and tested over time. The Arrhenius equation relates reaction rate constants at different temperatures, allowing prediction of shelf life at normal storage conditions from accelerated data. Limitations include reactions not dependent on temperature alone and products losing integrity at high stresses.
The document discusses pilot plant scale-up techniques. A pilot plant allows examination of a product and process on an intermediate scale before committing to full-scale production. It is important for identifying critical process parameters, producing samples for evaluation, and providing data to determine feasibility of full-scale production. The document outlines general considerations for pilot plant setup and operation including personnel requirements, equipment needs, production rates, process evaluation, and GMP compliance.
This document discusses guidelines for analytical method validation. It outlines types of analytical methods that require validation including chromatographic, spectroscopic, and dissolution methods. Key analytical performance characteristics used in validation are described such as specificity, linearity, range, accuracy, precision, detection/quantitation limits, robustness, and system suitability testing. The document provides details on determining these characteristics and validating methods. It also addresses revalidation and references for further information.
This document provides information about tablets, including their definition, categories, in-process tests, and testing methods. Tablets are solid oral dosage forms containing medicaments. There are several categories including uncoated, film coated, sugar coated, and modified release tablets. In-process tests include uniformity of contents, weight, dissolution, and disintegration. Dissolution and disintegration tests are described for different tablet types using specified apparatus, media, and time/acceptance criteria. Modified and prolonged release tablets have additional dissolution testing methods and criteria for acid and buffer stages.
The document discusses evaluation and stability studies of tablets. It provides details on common tablet tests performed during evaluation including general appearance, hardness, friability, weight variation, disintegration, and dissolution. It also discusses factors affecting drug stability and the various types of stability that must be considered, including chemical, physical, microbiological, therapeutic, and toxicological stability. Guidelines for stability testing from ICH, USP, FDA and other organizations are also summarized regarding testing conditions, frequency, and requirements for re-testing tablets after registration.
Hardness, friability, thickness, disintegration, weight variation, content uniformity, and dissolution are important quality control tests conducted on tablets. Hardness ensures tablets can withstand handling and processing, while friability measures how well tablets withstand abrasion. Disintegration tests how long it takes for tablets to break down, and weight variation and content uniformity ensure all tablets contain the intended amount of active drug. Dissolution testing determines how quickly the drug is released from the tablet in the body. Documentation of all quality control test results is necessary.
This document summarizes the standards and testing methods for different types of tablets according to the Indian Pharmacopoeia. It describes 10 types of tablets and the standards that apply to all tablets, including content uniformity, weight variation, disintegration, friability, and dissolution testing. The document provides details on the acceptance criteria and testing procedures for each of these standards.
Factors affecting drug stability include temperature, pH, buffering species, ionic strength, and dielectric constant. Temperature is an important factor because most reactions proceed faster at higher temperatures according to the Arrhenius equation. pH also affects stability, with most drugs being stable between pH 4-8, as hydrogen and hydroxide ions can catalyze degradation reactions. Buffering species like hydrogen and hydroxide ions participate in formation and breakdown of reaction intermediates. Ionic strength influences rates of reactions between ionic species, while dielectric constant affects rates of ion-dipole and ion-ion reactions. These physicochemical factors must be considered in stability testing and shelf life determination of pharmaceutical products.
Pharmaceutical degradation can occur through physical, chemical, or microbiological processes. Physical degradation includes changes in appearance, properties like hardness or consistency, and polymorphic changes. Chemical degradation involves reactions like hydrolysis, oxidation, decarboxylation, isomerization, and polymerization that break down the drug. Microbial degradation is caused by microbial growth contaminating the product. Proper storage conditions and formulation design can help prevent degradation through control of factors like temperature, humidity, light exposure, and microbial contamination.
This document discusses chemical kinetics and drug stability. It begins by introducing chemical kinetics and its application to studying physical and chemical reactions in drugs and dosage forms. It then discusses the rates of different reaction orders (zero, first, second) and how to determine reaction order. Factors that can affect reaction rates are also covered. The document outlines methods for stability testing of drugs and formulations to ensure patient safety, legal compliance and product quality. It discusses causes of drug instability and approaches to prevent or delay degradation, including accelerated stability testing. Stability considerations for semi-solid and solid dosage forms are also addressed. Finally, international regulatory guidelines for stability studies from ICH and WHO are mentioned.
The document discusses the Master Formula Record (MFR), which contains all information about the manufacturing process for a pharmaceutical product. It is prepared by the research and development team and used as a reference standard for preparing batch manufacturing records. The MFR includes details like product name, ingredients, batch size, manufacturing process steps, packaging process, and expected yields. It provides standardized instructions for consistently producing batches of a product.
Accelerated stability testing is used to predict the shelf life of pharmaceutical formulations by subjecting them to elevated temperatures and humidity to accelerate any degradation. The key steps involve conducting studies at different temperatures, determining the reaction order, calculating rate constants (k) at each temperature, determining the energy of activation using the Arrhenius equation, and extrapolating to room temperature to estimate shelf life. Limitations include changes in degradation mechanism or order at higher temperatures that limit the accuracy of shelf life predictions.
This document discusses drug stability and factors that affect it. It defines drug stability as a drug product remaining within established specifications for identity, strength, quality and purity. Factors like temperature, humidity, light and microbial contamination can cause drug degradation through chemical, physical and biological processes like hydrolysis, oxidation and photolysis. The document outlines various packaging materials and how they can impact stability. It also describes different types of stability studies conducted, including long-term real-time testing and accelerated methods like elevated temperature to evaluate products' shelf lives under normal conditions.
This document discusses guidelines from the International Council for Harmonisation (ICH) for stability testing of drug substances and products. It provides guidance on topics such as the need for harmonized stability testing, types of stability testing, selection of batches and storage conditions for testing, and evaluation of stability data. The guidelines aim to establish a systematic approach to stability testing to ensure quality, safety and efficacy over a product's shelf life and recommend conditions for testing drug substances intended for various storage conditions.
The International Conference on Harmonisation (ICH) was created in 1990 as a unique effort between regulators and industry from the EU, Japan, and US to harmonize technical requirements for pharmaceutical registration. ICH aims to ensure safety, efficacy, and quality of medicines while preventing duplicative trials and minimizing animal testing. Through guidelines developed via consensus building among members, ICH has harmonized requirements for drug development and approval processes. However, some concerns remain regarding inclusion of non-members in the decision making and implications for developing countries.
The document discusses guidelines for stability testing from the International Conference on Harmonisation (ICH). It provides an overview of several ICH guidelines related to stability testing of drug substances and products, including guidelines on photostability testing, new dosage forms, bracketing and matrixing designs, and evaluation of stability data. It also summarizes key aspects of conducting stability studies such as selecting representative batches, appropriate container closure systems, testing frequency and storage conditions, and evaluation of results. Stress testing is discussed as a way to validate analytical methods and identify potential degradants.
The International Council for Harmonisation (ICH) brings together regulatory authorities and the pharmaceutical industry to discuss technical requirements for drug registration. ICH has produced guidelines on quality, safety, efficacy, and multidisciplinary topics. The quality guidelines cover stability testing, analytical validation, impurities, Good Manufacturing Practice, and quality risk management. Together, the ICH guidelines aim to harmonize technical requirements across regions to provide efficient drug development and approval.
This document summarizes the ICH guideline for stability testing. The ICH provides guidance on stability testing to ensure drug quality over time under various environmental conditions. Key aspects covered include the objectives of stability testing, variables that affect stability, terminology, and ICH guidelines Q1A through Q1F which provide detailed recommendations on stability testing procedures, data evaluation, and submissions for registration.
Scale up and post approval changes(supac)bdvfgbdhg
The document discusses guidelines for post-approval changes to drug products, including changes to batch size, manufacturing sites and equipment, and composition. It outlines 3 levels of changes - minor, moderate, and major - and provides recommendations for documentation and regulatory filings required for each level of change. Major changes, such as a new manufacturing site or changes in the amount of active ingredients, require more extensive documentation including stability testing and possibly bioequivalence studies.
This document summarizes guidelines for stability testing of biotechnological and biological products. It discusses factors that can affect stability, including temperature, humidity, light and container materials. The guidelines specify conducting real-time stability studies at the proposed storage temperature and testing potency, purity and degradation over time. Manufacturers must propose a stability-indicating profile and validate methods to detect any changes to the identity, purity or potency of the product.
The document discusses the objectives and guidelines of the International Council for Harmonization (ICH) for stability testing of pharmaceutical products. It provides an overview of the key ICH guidelines for stability testing (Q1A-Q1F) and describes the principles of stability testing including establishing re-test periods and shelf lives. It also discusses the different types of stability testing, protocols, study designs like bracketing and matrixing, and key parameters for evaluation.
ICH Q10 provides a harmonized model for a pharmaceutical quality system throughout the lifecycle of a product. It describes a quality management system for the pharmaceutical industry. The objectives of the Q10 model are to achieve product realization, establish and maintain a state of control, and facilitate continual improvement. ICH Q10 covers pharmaceutical development, technology transfer, commercial manufacturing, and product discontinuation. It is intended to enhance existing good manufacturing practice requirements and be used together with them.
Accelerated stability testing exposes pharmaceutical products to elevated temperatures and humidity to rapidly determine their shelf life. Samples are stored at conditions like 40°C/75%RH and tested over time. The Arrhenius equation relates reaction rate constants at different temperatures, allowing prediction of shelf life at normal storage conditions from accelerated data. Limitations include reactions not dependent on temperature alone and products losing integrity at high stresses.
The document discusses pilot plant scale-up techniques. A pilot plant allows examination of a product and process on an intermediate scale before committing to full-scale production. It is important for identifying critical process parameters, producing samples for evaluation, and providing data to determine feasibility of full-scale production. The document outlines general considerations for pilot plant setup and operation including personnel requirements, equipment needs, production rates, process evaluation, and GMP compliance.
This document discusses guidelines for analytical method validation. It outlines types of analytical methods that require validation including chromatographic, spectroscopic, and dissolution methods. Key analytical performance characteristics used in validation are described such as specificity, linearity, range, accuracy, precision, detection/quantitation limits, robustness, and system suitability testing. The document provides details on determining these characteristics and validating methods. It also addresses revalidation and references for further information.
This document provides information about tablets, including their definition, categories, in-process tests, and testing methods. Tablets are solid oral dosage forms containing medicaments. There are several categories including uncoated, film coated, sugar coated, and modified release tablets. In-process tests include uniformity of contents, weight, dissolution, and disintegration. Dissolution and disintegration tests are described for different tablet types using specified apparatus, media, and time/acceptance criteria. Modified and prolonged release tablets have additional dissolution testing methods and criteria for acid and buffer stages.
The document discusses evaluation and stability studies of tablets. It provides details on common tablet tests performed during evaluation including general appearance, hardness, friability, weight variation, disintegration, and dissolution. It also discusses factors affecting drug stability and the various types of stability that must be considered, including chemical, physical, microbiological, therapeutic, and toxicological stability. Guidelines for stability testing from ICH, USP, FDA and other organizations are also summarized regarding testing conditions, frequency, and requirements for re-testing tablets after registration.
Hardness, friability, thickness, disintegration, weight variation, content uniformity, and dissolution are important quality control tests conducted on tablets. Hardness ensures tablets can withstand handling and processing, while friability measures how well tablets withstand abrasion. Disintegration tests how long it takes for tablets to break down, and weight variation and content uniformity ensure all tablets contain the intended amount of active drug. Dissolution testing determines how quickly the drug is released from the tablet in the body. Documentation of all quality control test results is necessary.
This document summarizes the standards and testing methods for different types of tablets according to the Indian Pharmacopoeia. It describes 10 types of tablets and the standards that apply to all tablets, including content uniformity, weight variation, disintegration, friability, and dissolution testing. The document provides details on the acceptance criteria and testing procedures for each of these standards.
Factors affecting drug stability include temperature, pH, buffering species, ionic strength, and dielectric constant. Temperature is an important factor because most reactions proceed faster at higher temperatures according to the Arrhenius equation. pH also affects stability, with most drugs being stable between pH 4-8, as hydrogen and hydroxide ions can catalyze degradation reactions. Buffering species like hydrogen and hydroxide ions participate in formation and breakdown of reaction intermediates. Ionic strength influences rates of reactions between ionic species, while dielectric constant affects rates of ion-dipole and ion-ion reactions. These physicochemical factors must be considered in stability testing and shelf life determination of pharmaceutical products.
Pharmaceutical degradation can occur through physical, chemical, or microbiological processes. Physical degradation includes changes in appearance, properties like hardness or consistency, and polymorphic changes. Chemical degradation involves reactions like hydrolysis, oxidation, decarboxylation, isomerization, and polymerization that break down the drug. Microbial degradation is caused by microbial growth contaminating the product. Proper storage conditions and formulation design can help prevent degradation through control of factors like temperature, humidity, light exposure, and microbial contamination.
This document discusses chemical kinetics and drug stability. It begins by introducing chemical kinetics and its application to studying physical and chemical reactions in drugs and dosage forms. It then discusses the rates of different reaction orders (zero, first, second) and how to determine reaction order. Factors that can affect reaction rates are also covered. The document outlines methods for stability testing of drugs and formulations to ensure patient safety, legal compliance and product quality. It discusses causes of drug instability and approaches to prevent or delay degradation, including accelerated stability testing. Stability considerations for semi-solid and solid dosage forms are also addressed. Finally, international regulatory guidelines for stability studies from ICH and WHO are mentioned.
The document contains details about a student named Srikanth Bandi enrolled in the Pharmaceutics department. It discusses accelerated stability testing, which involves exposing pharmaceutical products to elevated temperatures to simulate long-term shelf conditions over a shorter time period. The objectives and guidelines from the ICH are outlined, including storage conditions, sampling times, and test parameters. The document also describes the equipment used and process for conducting accelerated stability studies.
GCE A LEVEL TOPIC: (A2) CHEMICAL KINETICS
PLEASE DOWNLOAD BECAUSE THERE ARE MANY ANIMATIONS THAT HIDE SOME OF THE CONTENTS (THE ANIMATIONS DO NOT PLAY DURING THE PREVIEW)
Chemical Kinetics: Factors affecting reaction ratesMariel Catorce
This document discusses factors that affect chemical reaction rates through a series of experiments. It examines how the nature of reactants, surface area, concentration, temperature, catalysts, and enzymes influence the speed of reactions. Specifically, it found that finer particles of zinc powder reacted faster than zinc moss due to greater surface area exposure. It also determined reactions were faster at higher concentrations of reactants and higher temperatures due to more collisions and collision energy. The presence of catalysts like copper and enzymes like amylase also increased reaction rates.
First order kinetics describes a process where the rate of reaction is directly proportional to the concentration of the reactant. The rate increases linearly as the concentration increases. The concentration decreases over time but the reaction is never complete. Drug metabolism often follows first order kinetics, where a constant fraction of the drug is metabolized per unit of time. This can be expressed by the rate equation dC/dt = -kC, where C is the concentration and k is the rate constant. The half-life of a first order reaction is calculated from the rate constant. Pseudo-first order kinetics can also describe drug elimination from tissue where high concentrations of tissue components interact with drugs.
This document provides an overview of chemical kinetics and reaction rates. It discusses topics such as reaction rate, rate laws, reaction orders, rate constants, factors that affect reaction rates like temperature, catalysts, and enzyme kinetics. Specific examples are also provided to illustrate concepts like first-order and second-order reactions, reaction mechanisms, and industrial catalytic processes like the Haber process and catalytic converters.
This document discusses kinetics, drug stability, and reaction orders. It defines kinetics as the study of reaction rates and mechanisms. Drug stability is the resistance of a drug to changes during storage and use, and is quantified by shelf life. Reaction orders (zero, first, second) determine how reaction rates depend on reactant concentrations. Determining the order allows calculation of rate constants and quantities like half-life from concentration-time data.
Chem 2 - Chemical Kinetics V: The Second-Order Integrated Rate LawLumen Learning
This document discusses chemical kinetics for second-order reactions. It explains that for a second-order reaction, the rate is proportional to the concentration of the reactant squared. The integrated rate law for a second-order reaction is derived as 1/[A]t = kt + 1/[A]0, where [A]t is the concentration at time t, k is the rate constant, and [A]0 is the initial concentration. If a plot of 1/[A] versus time is linear, then the reaction is second-order. The half-life of a second-order reaction depends on the initial concentration and is calculated as t1/2 = 1/k[A]0.
Chem 2 - Chemical Kinetics III - Determining the Rate Law with the Method of ...Lumen Learning
This document discusses determining the rate law for a chemical reaction through initial rate experiments. It explains that the rate of reaction depends on reactant concentrations and describes how to find the orders of each reactant by comparing how the rate changes with concentration changes. The orders are used to define the rate law expression. Experimental data is then used to calculate the numeric rate constant.
This document provides an overview of stability considerations, pathways, and assays for pharmaceutical products. It discusses theoretical concepts of stability, factors affecting stability like temperature, moisture and containers. It outlines different types of stability to consider like chemical, physical, and microbiological. Regulatory requirements for stability studies from agencies like ICH, USP, and FDA are mentioned. Common degradative pathways like physical degradation, chemical degradation via oxidation, decarboxylation etc. are summarized. The document concludes by outlining stability indicating assays.
INTRODUCTION
FACTORS EFFECTING STABILITY
OBJECTIVE
TYPES OF STABILITY
TYPES OF STABILITY THAT MUST BE CONSIDERED FOR ANY DRUG
REGULATORY REQUIREMENTS
STABILITY STUDIES FOR PHARMACEUTICAL PRODUCTS
DEGRADATIVE PATHWAYS
Stability studies are performed in life sciences, chemical, and food and beverage industries to determine the effects of environmental conditions on product quality. Environmental conditions can impact product shelf life, and the viability of product formulation.
DEFINATION
The capacity of a drug or product to remain within established specifications of identity, quality, purity in a specific period of time.
The capacity or the capability of a particular formulation in a specific container to remain with in particular chemical, microbiological, therapeutically, and toxicological specifications.
USP defines stability of pharmaceutical product as, "extent to which a product retains with in specified limits and throughout its period of storage and use (i.e. shelf life).
The capacity or the capability of a particular formulation in a specific container to remain with in particular chemical, microbiological, therapeutically, and toxicological specifications.
USP defines stability of pharmaceutical product as, "extent to which a product retains with in specified limits and throughout its period of storage and use (i.e. shelf life).
The primary factors effecting stability:
PH, Temperature, Moisture, humidity, light, Storage closure and containers Oxygen.
The major factors effecting drug stability are:
Particle size (suspension and emulsion), PH, additives and molecular binding and diffusion of drugs and excipients.
Stability testing of natural products.docxKipaPape
Stability is defined as the capacity of drug to remain within established specification limits to maintain its identity, strength, quality and purity throughout the retest or expiration dating period.
It is the ability of formulations to retain its physical, chemical, microbiological and toxicological parameters same that time of manufacturer.
This document discusses preformulation stability studies. It outlines the key factors that affect drug stability like temperature, moisture, and light. The objectives of stability testing are to determine shelf life and provide better storage conditions. The main types of stability are chemical, physical, microbiological, therapeutic, and toxicological. Various methods for stability testing include real-time testing, accelerated testing, and retained sample testing. Guidelines for long-term stability testing from ICH are presented. Common dosage forms that undergo stability testing are discussed.
Stability testing of herbal products involves subjecting samples to various conditions like heat, light, and humidity to determine shelf life and ensure quality over time. Key aspects of stability testing include establishing acceptance criteria and storage conditions, conducting both accelerated and long-term real-time tests, and developing a protocol that specifies test attributes, analytical methods, sampling plans, and evaluation procedures. Challenges with testing herbal products relate to their complex compositions, but can be addressed through marker analyses and fingerprinting techniques. Proper stability testing is important for determining appropriate packaging, storage, and expiry dates.
The document discusses the importance of stability studies for pharmaceutical products to determine shelf-life and ensure quality, safety, and efficacy over time. It outlines regulatory guidelines for stability testing, including storage conditions and frequencies of analysis. The interpretation of stability study results and conclusion that testing must be done according to specifications throughout a product's shelf-life are also summarized.
Introduction to Stability Testing of Drugs and Cosmetics. Includes the 3 types of stability test methods (Real time studies, Accelerated studies and Stress tests). Contains the WHO and ICH Climatic Zones for Real time, Intermediate and Accelerated tests). Classification of Packaging materials. Container- Closure Systems.
This document summarizes ICH guidelines for stability testing of drug substances and products. It discusses the key topics covered by ICH Q1 including stability protocols, studies at different storage conditions, evaluation of stability data, and design approaches like bracketing and matrixing. The guidelines provide recommendations for parameters to test at different timepoints under long term, intermediate, and accelerated conditions. Statistical analysis of batch variability is important to establish a retest or expiry date. Photostability testing and requirements for new dosage forms are also outlined. Overall the ICH Q1 guidelines aim to standardize stability testing practices to ensure quality, safety and efficacy of drugs over their shelf life.
Accelerated stability studies are conducted to increase the rate of chemical degradation or physical change of a drug product by using exaggerated storage conditions. The Arrhenius equation describes the dependence of the reaction rate constant on temperature and can be used to extrapolate accelerated stability data to long-term storage conditions. Types of accelerated stability tests include those at elevated temperatures, high intensity light, high partial pressure of oxygen, and high relative humidity. However, accelerated stability testing has limitations when degradation is caused by factors other than temperature, such as microbial contamination or diffusion, or when a product loses physical integrity at higher temperatures. International guidelines provide recommendations for conducting stress tests and evaluating stability data.
Stability testing protocol for herbal products in a detailed review.It’s the ability of formulation to retain its physical, chemical, microbiological and toxicological parameter same as that time of manufacture .
Drug product remains within specifications established to ensure its identity, strength, quality and purity.
Stability – Chemical and Physical integrity of herbal medicinal products.
Over a given time period and under the influence of environmental factors including temperature, humidity and light.
To provide evidence on how the quality of active substance varies with time and environmental factors
To establish re- test period for active substance
To establish shelf life of finished products.
To recommend storage conditions.
To evaluate the efficacy of drug.
To develop suitable packing information for drug product
To submit stability information for regulatory agencies.
1.Physical stability study:-
The original physical properties namely appearance, uniformity, palatability, dissolution, and suspend ability are maintained.
Chemical stability study:-
Each and every active ingredient retains its chemical integrity as well as potency specified on label, within the specified limits.
It involves drug assay and determination of drug degradation.
Stability_Considerations_In_Formulation_Development.pptRavi Kumar G
The document discusses the importance of stability considerations in pharmaceutical development. It states that stability is a key attribute and integral part of drug and dosage form development. The aim of pharmaceutical development is to design stable products and control factors preventing quality and stability issues. Stability evaluations start early in drug development and cover various stages. The physical state of drugs can influence stability, dissolution, and bioavailability. Factors like polymorphism, hydration, and processing need to be controlled. Excipient selection and manufacturing processes also impact stability and should be considered during formulation development.
That presentation is about the stability of the drug, why it's necessary?? What is the shelf life of a drug? Purpose of stability testing and its importance.Also a review article of Sanjay Bajaj et al published in Journal of applied pharmaceutical sciences.
This document provides an overview of stability indicating method development. It defines key terms like stability, shelf-life, and stability indicating method. It describes the types of stability studies including accelerated and real-time. The main objectives and climatic zones for stability testing are outlined. Forced degradation studies and the approach to developing a stability indicating method through stress testing, method development/optimization, identification of degradation products, and validation are summarized. Critical issues like the need for stress testing and achieving mass balance are also discussed.
Solid state stability and shelf-life assignment, Stability protocols,reports ...Durga Bhavani
This document discusses guidelines for solid state stability and shelf-life assignment studies as outlined by ICH. It provides definitions of stability, the need for stability studies, and factors that influence drug degradation like temperature, moisture, light and interactions. The document outlines the types of studies, including real-time and accelerated stability studies. It discusses stability protocols, reports, and test conditions recommended by ICH to determine a drug's shelf life.
The document summarizes ICH guidelines for stability studies of new drug substances and products. It discusses the objectives and scope of stability testing, including providing evidence of a drug's quality over time under various environmental conditions to establish storage requirements and shelf life. The types of stability testing include chemical, physical, microbiological, therapeutic, and toxicological. Testing is conducted over various time periods and storage conditions as outlined in the ICH Q1A-Q1F guidelines. Evaluation of stability data includes assessing parameter results and using statistical analyses to determine a product's retest period or shelf life.
This document discusses guidelines for stability testing of pharmaceuticals according to the International Conference on Harmonization (ICH). It describes the ICH guidelines for stability testing, including stability protocols, reports, and studies. The key points covered include stability testing procedures, factors affecting drug stability, types of stability studies, and organizations that regulate stability guidelines such as the ICH.
ICH is an international organization that brings together regulatory authorities and pharmaceutical companies from Europe, Japan and the US to discuss guidelines for drug approval. The purpose is to harmonize technical requirements to reduce redundant testing and delays in approval processes while maintaining standards of quality, safety and efficacy. Stability testing provides evidence of how a drug's quality changes over time under different environmental conditions like temperature and humidity to establish appropriate storage conditions and shelf life. [/SUMMARY]
Stability testing is used to provide evidence of how the quality of a drug substance or product varies over time under environmental conditions like temperature, humidity, and light. Guidelines provide recommendations on conducting stability tests including storing samples under long-term, intermediate, and accelerated conditions and specifying the testing frequency. Stability tests evaluate attributes of the drug substance or product that may change during storage. The results are used to establish a retest period to ensure the stated quality of the substance or product through the expiration date.
1. A PRESENTATION ON : STABILITY THEORITICAL CONSIDERATION ,
DEGRADATIVE PATHWAYS, STABILITY INDICATING ASSAYS
Department of Pharmaceutics
School Of Pharmacy .
B.I.T. By Pass Road Partapur Meerut
Presented to : Presented By :
Dr. Upendra Nagaich Promila Sharan
Associate Professor M.Pharm -1 sem
(Pharmaceutics) (Pharmaceutics)
2. INTRODUCTION
STABILITY THEORITICAL CONSIDERATION
FACTORS EFFECTING STABILITY
OBJECTIVE
TYPES OF STABILITY
REGULATORY REQUIREMENTS
STABILITY STUDIES FOR PHARMACEUTICAL PRODUCTS
DEGRADATIVE PATHWAYS
PHYSICAL DEGRADATION
CHEMICAL DEGRADATION
STABILITY INDICATING ASSAY
3.
4. STABILITY – THEORITICAL CONSIDERATION
The capacity of a drug or product to remain within established
specifications of identity , quality, purity in a specific period of time.
OR
The capacity or the capability of a particular formulation in a specific
container to remain with in particular chemical , microbiological ,
therapeutically , and toxicological specifications.
USP defines stability of pharmaceutical product as , “extent to which a
product retains with in specified limits and throughout its period of
storage and use ( i.e. shelf life).
5. It is defined as the time required for the concentration of the reactant to
reduce to 90% of its initial concentration .Represented as t90 and the
units of time /conc.
t90 = (a-0.9a) = 0.1 a
ko ko
Where , a = initial concentration .
ko = specific rate constant for zero order reaction.
(the time from the date of manufacture and packaging of the formulation
until its chemical or therapeutic activity is maintained to a predetermined
level of labeled potency and ,
its physical characteristic have not changed appreciably or deleteriously ).
6. FACTORS EFFECTING DRUG STABILITY
The primary factors effecting stability :
PH , Temperature , Moisture , humidity , light , Storage closure and containers
, Oxygen
The major factors effecting drug stability are :
Particle size (suspension and emulsion) , PH , additives and molecular binding
and diffusion of drugs and excipients .
OBJECTIVES
1. To determine maximum expiration date/ shelf life.
2. To provide better storage condition.
3. To determine the packaging components.
4. To gather information during preformulation stage to produce a stable
product.
7. THEARAPEUTICAL
STABILITY
CHEMICAL PHYSICAL
STABILITY STABILITY
I
AM
STABLE
MICROBIOLOGIC
TOXICOLOGIC
AL
STABILITY
STABILITY
8. TYPES OF STABILITY THAT MUST BE
CONSIDERED FOR ANY DRUG
CHEMICAL
Each active ingredient retains its chemical integrity and labeled potency within the
specified limit.
PHYSICAL
The physical stability properties includes appearance, palatability ,uniformity
,dissolution and suspendability are retained.
MICROBIOLOGICAL
Sterility or resistance to microbial growth is retained according to specified
requirement.
THERAPEUTIC
Therapeutic activity remains unchanged .
TOXICOLOGIC
No significant increase in toxicity occurs.
9. Stability study requirement and expiration dates are
covered in the current GMP , USP and FDA
GMP (Good Manufacturing Practice) states that there
will be written testing program design to access the
stability characteristics of drug products . And result of
such stability testing will be used to determine
appropriate storage condition and expiration dates
10. ICH GUIDELINES FOR STYABILITY TESTING
The ICH has so far released six guidelines for stability studies as indicated in table :
ICH GUIDELINES TITLE
Q1A Stability testing of new drug substances and products (second revision)
Q1B Stability testing : photo stability testing of new drug substance and
products.
Q1C Stability testing for new dosage forms
Q1D Bracketing and matrixing designs for stability testing of drug substances
and products
Q1E Evaluation of stability data
Q1F Stability data package for registration application in climatic zones III
and IV
CLIMATIC ZONES
AS per ICH and WHO guidelines ,world has been divided into four zones :
ZONE 1 - TEMPERATE
ZONE2 - SUBTROPICAL WITH POSSIBLE HIGH HUMIDITY
ZONE 3 - HOT, DRY
ZONE 4 - HOT,HUMID
11. LONG TERM STABILITY STUDIES :
According to WHO, long term stability testing during and beyond expected shelf life
under storage conditions in the intended market.
RECOMMENDED CONDITIONS FOR LONG TERM STABILITY
STORAGE CONDITIONS
TEMPERATURE („C) RELATIVE HUMIDITY% MINIMUM TIME
25‟C+/- 2‟C 60 +/- 5% 12 MONTHS
30‟C +/- 2‟C 30+/- 5% 6 MONTHS
ACCELERATED STABILITY STUDIES:
STORAGE CONDITIONS
TEMPERATURE („C) RELATIVE HUMIDITY% MINIMUM TIME
40‟C +/- 2‟C 75 +/-5% 6 MONTHS
In , general the accelerated stability conditions must be at least 15‟C above the
actual storage temperature and appropriate relative humidity . Substances and
drugs products intended to be stored in a refrigerator . the accelerated stability
studies should be carried out at 25+/-2‟c and 60+/-5% relative humidity.
12. RELATIVE HUMIDITY
Relative humidity is the ratio of the partial
pressure of water vapor in an air water
mixture to the saturated vapor pressure of
water at prescribed temperature.
Relative humidity depends on temperature
and pressure.
13. TABLET
Stable tablets retain their original size ,shape , weight ,roughness ,colour variation ,
cracking under normal handling and storage conditions throughout their shelf life.
• FRIABILITY TEST : studies revel the physical instability if any in tablet.
Maximum weight loss should not be more than 1%.
• HARDNESS TEST : shows resistance to crushing.
• COLOR STABILITY : by colorimeter , reflectometer with heat , sunlight and intense
artificial light.
Uniformity of weight , odor , texture , drug and moisture content , humidity effects
are also Studied during a tablet test.
14. GELATINE CAPSULE
Gelatin capsules are found to be stable in dry
conditions but they rapidly reach equilibrium with
the atmospheric conditions under they are stored.
This shows gelatin capsules are largely effected by
temperature and humidity and susceptibility to
microbial degradation .
soft gelatin capsule have Relative Humidity 20 to
30% at 21 to 24’C.
hard gelatin capsule contain 13 to 16% moisture.
Humidity - capsule shell softens and becomes
sticky.
Dried- capsule shell becomes brittle and crack.
Hard gelatin capsule are tested for Brittleness ,
dissolution , water content and level of microbial
contamination.
15. EMULSIONS
Tested for phase separation , PH , viscosity , level of microbial
contamination , and distribution of dispersed globules.
ORAL SOLUTIONS AND SUSPENSIONS
Formation of precipitate , clarity for solutions , PH , viscosity ,
microbial contamination.
Additionally for suspensions , redispersibility , rheological
properties ,mean size and distribution of particles should be
considered .
NASAL SPRAYS : solution and suspensions
Clarity (for solution) , level of microbial contamination , PH ,
particulate matter , unit spray medication , content uniformity
, droplet and/or particle size distribution , weight loss , pump
delivery.
Microscopic evaluation ,(for suspension) , foreign particulate
matter and extractable/ leachable from components of the
container , closure and pump.
TOPICAL , OPTHALMIC AND OTIC PREPRATION
Included in this broad category are ointments ,creams , lotions
,paste , gel , solutions ,eye drops and cutaneous sprays.
16. TOPICAL
preparations should be evaluated for clarity , homogeneity , PH ,
resuspendibility for lotions , consistency , viscosity , particle size
distribution ,level of microbial contamination / sterility and weight
loss
FOR OPTHALMIC OR OTIC PREPRATION
Should include the following additional attributes : sterility
,particulate matter ,and extractable.
SUPPOSITORIES
Softening range , dissolution (at 37’C)
PARENTERALS
Color , clarity (for solutions) , particulate matter , PH, sterility ,
pyogen / endotoxins .
Stability studies for powders for injection solution ,include color
monitoring , reconstitution time and water content ,to be performed
at regular intervals .
17. DEGRADATIVE PATHWAYS OF PHARMACEUTICAL
DOSAGE FORMS
Degradation of active drug leads to lowering of quantity of the therapeutic agent in the dosage form.
It may not be extensive , a toxic product formation may take place due to decomposition instability of
drug product can lead to a decrease in its bioavailability .
Changes in physical appearance of given dosage form may take place.
Degradation may increase or may decrease the potency of drug.
Sometimes active drug may retain its potency , but excipients like – antimicrobial , preservatives ,
solubilizers , emulsifying or suspending agent may degrade , lead to compromising the integrity of drug
product.
EXAMPLE :
Drugs like 5-fluorouracil , carbamazipine , digioxin and theophylline have narrow therapeutic indices
these needs to be carefully treated in patient so that plasma levels are neither too high as to be toxic nor
too low as to be ineffective
The antimicrobial chloroquine can produce toxic reactions that are attribute to the photochemical
degradation of the substance.
18. DEGRADATION MAY BE OF TWO TYPES
PHYSICAL DEGRADATION
CHEMICAL DEGRADATION
• OXIDATION
• DECARBOXYLATION
• PHOTOLYSIS
• RACEMIZATION
• HYDROLYSIS
PHYSICAL DEGRADATION
The physical stability properties includes appearance, palatability ,uniformity ,dissolution and
suspend ability are retained . Maintained throughout the shelf life of the drug.
IT INCLUDES FOLLOWING :
Loss of water
loss of volatile oil
Water Absorbance
Polymorphism
Color change
19. Physical degradation includes following :
LOSS OF VOLATILE CONTENT: Volatile compounds used such as
Alcohol ether , camphor oils , etc . Try to escape from the formulation leads to degradation of
formulation.
Example : nitroglycerine from drugs evaporate.
LOSS OF WATER : Water loss from liquid preparation (o/w emulsion) leads to changes in stability .
Itcauses crystallization of drug product .which may lead to increase in potency , and decrease in
weight.
Example : water evaporates from Na2SO4 .BORAX.
WATER ABSORBANCE : pharmaceutical formulations which are hygroscopic in nature absorb the
water from its external environment leads to degradation .
Example :gelatin capsule , deliquescent salts like –Cacl3 , Potassium citrate.
POLYMORPHISM: A stable crystal form is effected (it may loosen) leads to the formation of
polymorph and cause instability in formulation. This may lead to alteration in solubility , dissolution of
drug
COLOR CHANGE: Loss or development of color may occur .
(due to change in PH , use of reducing agent , exposure to light )
20. CHEMICAL DEGRADATION
Chemical degradation of a dosage form occurs through several pathways like –hydrolysis ,oxidation ,
decarboxylation , photolysis , racemization .which may lead to lowering of therapeutic agent in the dosage
form ,formation of toxic product , decreased bioavailability etc.
HYDROLYSIS
Most important in systems containing water such as emulsion , suspension , solutions , etc.
Also for drugs which are affected by moisture (water vapor) from atmosphere.
It is usually catalysed by hydrogen ion(acid) or hydroxyl ion(base).
In this active drug is decomposed with solvent.
Usually solvent is water some time reaction may involve pharmaceutical co solvents such as ethyl alcohol
or poly ethylene glycol
Main classes of drugs that undergo hydrolysis are the ESTERS ,AMIDE ,ALKALI, ACID.
ESTER HYDROLYSIS involve acyl – acid cleavage.
Example of drugs: aspirin ,atropine , physostigmine , procaine..
R .COOR (ester) + H2O RCOOH (acid) + HOR(alcohol)
AMIDE HYDROLYSIS is more stable than ester , susceptible to specific and general acid base hydrolysis. It
involves cleavage of amide linkage to give an amine instead of alcohol as in case of esters.
Example of drugs : chloramphenicol , barbiturates .
RCONHR(amide) + H2 O RCOOH + NH2 R(AMINE)
21. PROTECTION AGAINST HYDROLYSIS
Avoiding contact with moisture at time of manufacture.
Packaging in suitable moisture resistant packs such as strip packs and storage in controlled
humidity and temperature.
In liquid dosage form since , hydrolysis is acid or base catalyzed , an optimum PH for max
stability should be selected and the formulation should be stabilized at this PH by inclusion of
proper buffering agents.
Hydrolysis of certain drugs such as benzocaine and procaine can be decreased by the addition
of specific complexing agent like caffeine to the drug solutions .
Hydrolysis susceptible drugs such as penicillin and derivatives can be prevented by
formulating them in the dry powder form for reconstitution or dispersible tablets instead of a
liquid dosage form such as solutions or suspensions.
22. OXIDATION
Oxidation is controlled by environment i.e, light ,trace elements , oxygen and oxidizing agent
.
Occurs when exposed to atmospheric oxygen.
Either the addition of oxygen or removal of hydrogen .
Oxidation is the loss of electrons while reduction is the gain of electrons.
AUTOXIDATION
The reaction between the compounds and molecular oxygen is required for initiating the
chain reaction is called autoxidation .
Free radicals produced during initial reaction are highly reactive and further catalyze the
reaction produced additional free radicals and causing a chain reaction.
Heavy metals such as copper , iron , cobalt , and nickel have been known to catalyze the
oxidative degradation .Heat and light further influence the kinetics of oxidative degradation
processes.
23. STEPS INVOLVED OXIDATION REACTION
INITIATION : Formation of free radicals is taken place .
R--H R’ + [H’}
PROPOGATION : here the free radical is regenerated and react with more oxygen .
R’ + O2 R’—O2
R’O2 + RH ROOH + R’
HYDROPEROXIDE DECOMPOSITION
ROOH RO’ + OH’
TERMINATION : free radicals react with each other resulting in inactive products.
R’--O2 + X Inactive product
RO2 + RO2 Inactive product
EXAMPLE OF DRUGS DECOMPOSED BY OXIDATION PATHWAYS
Archis oil , clove oil , ethyl oleate ,Heparin , Ascorbic acid , Morphine ,Vitamin A , Vitamin
B12 , etc.
24. PROTECTION AGAINST OXIDATION
USE OF ANTIOXIDANTS : antioxidants are Mainly of 3 types :
1. The first group probably inhibits the oxidation by reacting with free radicals.
Example – tocopheral , butylated hydroxyl anisole (BHA) , butylated hydroxyl
toluene's (BHT). Concentration 0.001 – 0.1%.
2. The second group comprising the reducing agents , have a lower redox
potential than the drug or other substance that they should protect and are
therefore more readily oxidized.
Example –ascorbic acid and iso ascorbic acid , potassium or sodium salts of
metabisulfite.
3. The third group, little antioxidant effect themselelf but enhance the action of
true antioxidant .example
Example -- Citric acid , tartaric acid , disodium edetate and lecithin .
USE OF CHELATING AGENT when heavy metals catalyze oxidation .
Example -- EDTA , citric acid , tartaric acid form complexes.
25. PHOTOLYSIS
Exposure to light cause substantial degradation of drug molecule.
•When molecules are exposed to electromagnetic radiation they
absorb light (photons) at characteristic wavelength which cause
increase in energy which can :
Cause decomposition.
Retained or transferred.
Be converted to heat .
Result in light emission at a new wavelength (fluorescence ,
phosphorescence).
• Natural sun light lies in wavelength range (290– 780nm) of
which only higher energy (UV) range (290 --320) cause photo
degradation of drugs.
`
26. Example of phototoxic drugs:
Furosemide , acetazolamide , cynocobalamine .
EXAMPLE
Sodium nitropruside in aqueous solution (which
is administered by IV infusion for
management of acute hypertension ).
If protected from light it is stable to at least 1yr.
If exposed to normal room light it has a shelf life
of 4 hrs.
PROTECTION
Use of amber colored bottles .
Storing the product in dark , packaging in cartons
also act as physical barrier to light.
Coating of tablets with polymer films.
27. STABILITY IDENTIFYING ASSAYS
It is a quantitative analytical method which is based on the characteristic structural ,
chemical , biological ,properties of each active ingredient of drug product and that
can differentiate between active pharmaceutical ingredient and its degradation
product accurately.
STABILITY INDICATING ASSAY DEVELOPMENT
Developing a stability indicating assay requires consideration of three aspects of
the method :
A. Obtaining a representative SAMPLE.
B. Choosing the separation techniques .
C. Selecting the detectors .
OBTAINING A REPRESENTATIVE SAMPLE
Pure drug compound degrades into toxic compound.
Formulation ----degradation drug (toxic) + inert (non-toxic).
28.
29. PREPRATION OF SAMPLE
Forced degradation .
Purposeful degradation .
• Drug is subjected to acid , base , heat , light , or oxidation .
• Goal is to degrade the drug.
• It should include 10-20% degradation & greater than 10—20% could result in
secondary
degradants that will complicate the development process.
Dissolving portion of sample in 0.1 N hydrochloric acid for acid degradation
and collect sample at interval of 1,2,4,8,24 hrs.
• Similarly reaction is quenched in BASE .
• FOR OXIDATION (with peroxides) ,collect sample.
• Resulting sample is analyzed by measuring loss of parent drug .
• Auto sampler vials can also be used ,injections at regular interval of 1hr.
• Observe sample change in time.
30. SEPERATION
REVERSE PHASE CHROMATOGRAPHY is the method of choice for stability
indicating assays because the samples are generated in aqueous solutions . (non polar
stationary phase).
•We should choose gradient elution for sample screening.
•Most commonly used solvent type are - acetonitrile , methanol.
•Low and intermediate PH are generally obtained by use of phosphate buffer in the PH
2.5 – 6.5 range.
•Ifmethod involve mass spectroscopy (MS) detector at same point ,select buffer that
are MS compatible such as 0.1 %trifluoroacetic acid .
•Column temperature (35—50’C).
•Core set of experiments should be 4runs for each sample.
•Afterthe screening runs are completed .Now match the peaks between runs so that
each compound can be tracked as the conditions change.
•Although each sample might contain only 4 or 6 significant degradants ,different
30degradation conditions can produce some of the same compounds in addition to
unique degradation.
31. THE DETECTORS
The mass spectrometer is detector of choice for many liquid
chromatography methods ,particularly for biological.
UV detector remains the detector of choice for stability indicating assay.
Assay must be capable to determine sample within at least 1000 fold conc.
. Range from 0.1 to 0.05 % of the parent drug.
MS detector can be very useful in identifying unknown peaks in the final
method.
DIODE ARRAY UV detector
Often are used during the development of a stability indicating assay .
Each compound could be detected at its absorbance maximum by using
individual maxima for routine detection.
By collecting a UV SPECTRUM for each peak in the chromatogram , peak
tracking can be simplified.
32. reference
K.Wolters ; “Rehmington The science and practice of pharmacy”;21st edition volume -
2005;published in Philadelphia College of Pharmacy and science”;page no – 1025 -1033.
J.S Ptrick ; “Martin‟s Physical pharmacy and pharmaceutical sciences”;5th edition ; published by
Wolters Kluver Health(India)Pvt. Ltd. New Delhi. Page no – 428-432.
L Lachman , K.Herbert A. ; “The Theory and Practice of Industrial Pharmacy” ; special Indian
edition 2009 ; CBS Publishers and Distributors Pvt. Ltd ;Page no – 772 ,777 ,849.
ICH Q1B : “Photostability Testing of New Drug Substances and Products”.
ICH Q1C : Stability Testing of New Dosage Forms”.