The document provides guidance on developing and validating dissolution testing procedures for solid oral dosage forms. It discusses preliminary steps like determining drug solubility and stability in different media, and choosing an appropriate medium, volume, filtration method and apparatus. It also outlines the method development process, including deaeration techniques, use of sinkers, agitation settings, study design considerations like time points and observations recorded, sampling methods, and data handling. The overall goal is to develop a discriminating and reproducible dissolution method and provide validation criteria.
This document discusses dissolution method development. It defines dissolution as a process where a solid substance enters a solvent to form a solution. The key steps in dissolution are wetting, disintegration, disaggregation, and dissolution of particles. Factors that influence dissolution are also discussed, along with the Noyes-Whitney equation. A systematic approach to method development is then outlined, including literature review, solubility studies, sink conditions, apparatus selection, media preparation, method optimization, and sample analysis investigations. The goal is to develop a successful dissolution method and analysis to characterize drug release.
Dissolution procedure development and validation, USP 1092Md. Saddam Nawaz
Ā
This document discusses the development and validation of dissolution procedures according to USP<1092>. It provides general comments on the purpose of dissolution testing and discusses key aspects of developing a discriminating and reproducible method, including choice of medium, apparatus, study design, sampling, and validation. The document outlines factors to consider for various dosage forms and provides examples of typical dissolution conditions and acceptance criteria.
The dissolution test is an important means of assuring the continuing performance of non-solution orally administered drug products. The development of a dissolution test procedure is briefly discussed in USP general information chapter In Vitro and In Vivo Evaluation of Dosage Forms 1088, whereas general information chapter Validation of Compendial Procedures 1225 gives limited validation information for dissolution testing. Neither of these two chapters provides a level of detail and focus sufficient for dissolution testing. In 2001, a Stimuli article provided an initial rationale and discussion of content for a new general information chapter. The new chapter, The Dissolution Procedure: Development and Validation 1092, was intended to supplement the information in 1088 and 1225 and provided step-by-step detail for development and validation as well as offering information on new technology and equipment. In 2006, the chapter became official with the Second Supplement to USP 29āNF 24 (2ā4).
The General ChaptersāDosage Forms Expert Committee 2010ā2015 placed the review and possible revision of The Dissolution Procedure: Development and Validation 1092 on its work plan for the 2010ā2015 revision cycle (2011) .
Drug Regulations has prepared this presentation based on the proposed chapter.
The document presents information on the development of dissolution methods. It discusses the processes involved in dissolution testing of solid oral dosage forms including that the drug must be released and dissolve in GI fluids to be absorbed. It also outlines factors that affect dissolution tests such as the apparatus, dissolution fluid, and process parameters. The document provides details on apparatus selection and types, as well as key elements of developing a dissolution method such as ensuring it is discriminatory, robust, and correlated to in vivo outcomes. Steps involved in method development like degassing, sinkers, agitation, sampling, and cleaning are also summarized.
This presentation highlights the reasons which lead to the withdrawal of the 2002 Guidance of the FDA and the current issue with Blend Uniformity and Content Uniformity Determinations.
This document discusses analytical method validation and cleaning validation in pharmaceutical manufacturing. It defines validation and outlines key parameters assessed in analytical method validation, including linearity, range, specificity, precision, accuracy, detection and quantitation limits, robustness, and system suitability. It also discusses objectives of cleaning validation, levels of cleaning, validation of cleaning processes and equipment, sampling methods, establishment of limits for residues, and documentation requirements. The overall purpose of validation is to demonstrate that processes can consistently produce products meeting specifications.
This document discusses methods for comparing drug dissolution profiles, which provide information about how completely and quickly an active pharmaceutical ingredient is released from its dosage form. Graphical and statistical methods are described for directly comparing dissolution curves. Model-dependent approaches apply kinetic models like zero-order, first-order, and Higuchi models to the data. Model-independent methods calculate similarity factors f1 and f2 that provide single values for comparing profiles. Comparing dissolution profiles is important for evaluating drug release and bioequivalence of pharmaceutical formulations.
This document discusses dissolution method development. It defines dissolution as a process where a solid substance enters a solvent to form a solution. The key steps in dissolution are wetting, disintegration, disaggregation, and dissolution of particles. Factors that influence dissolution are also discussed, along with the Noyes-Whitney equation. A systematic approach to method development is then outlined, including literature review, solubility studies, sink conditions, apparatus selection, media preparation, method optimization, and sample analysis investigations. The goal is to develop a successful dissolution method and analysis to characterize drug release.
Dissolution procedure development and validation, USP 1092Md. Saddam Nawaz
Ā
This document discusses the development and validation of dissolution procedures according to USP<1092>. It provides general comments on the purpose of dissolution testing and discusses key aspects of developing a discriminating and reproducible method, including choice of medium, apparatus, study design, sampling, and validation. The document outlines factors to consider for various dosage forms and provides examples of typical dissolution conditions and acceptance criteria.
The dissolution test is an important means of assuring the continuing performance of non-solution orally administered drug products. The development of a dissolution test procedure is briefly discussed in USP general information chapter In Vitro and In Vivo Evaluation of Dosage Forms 1088, whereas general information chapter Validation of Compendial Procedures 1225 gives limited validation information for dissolution testing. Neither of these two chapters provides a level of detail and focus sufficient for dissolution testing. In 2001, a Stimuli article provided an initial rationale and discussion of content for a new general information chapter. The new chapter, The Dissolution Procedure: Development and Validation 1092, was intended to supplement the information in 1088 and 1225 and provided step-by-step detail for development and validation as well as offering information on new technology and equipment. In 2006, the chapter became official with the Second Supplement to USP 29āNF 24 (2ā4).
The General ChaptersāDosage Forms Expert Committee 2010ā2015 placed the review and possible revision of The Dissolution Procedure: Development and Validation 1092 on its work plan for the 2010ā2015 revision cycle (2011) .
Drug Regulations has prepared this presentation based on the proposed chapter.
The document presents information on the development of dissolution methods. It discusses the processes involved in dissolution testing of solid oral dosage forms including that the drug must be released and dissolve in GI fluids to be absorbed. It also outlines factors that affect dissolution tests such as the apparatus, dissolution fluid, and process parameters. The document provides details on apparatus selection and types, as well as key elements of developing a dissolution method such as ensuring it is discriminatory, robust, and correlated to in vivo outcomes. Steps involved in method development like degassing, sinkers, agitation, sampling, and cleaning are also summarized.
This presentation highlights the reasons which lead to the withdrawal of the 2002 Guidance of the FDA and the current issue with Blend Uniformity and Content Uniformity Determinations.
This document discusses analytical method validation and cleaning validation in pharmaceutical manufacturing. It defines validation and outlines key parameters assessed in analytical method validation, including linearity, range, specificity, precision, accuracy, detection and quantitation limits, robustness, and system suitability. It also discusses objectives of cleaning validation, levels of cleaning, validation of cleaning processes and equipment, sampling methods, establishment of limits for residues, and documentation requirements. The overall purpose of validation is to demonstrate that processes can consistently produce products meeting specifications.
This document discusses methods for comparing drug dissolution profiles, which provide information about how completely and quickly an active pharmaceutical ingredient is released from its dosage form. Graphical and statistical methods are described for directly comparing dissolution curves. Model-dependent approaches apply kinetic models like zero-order, first-order, and Higuchi models to the data. Model-independent methods calculate similarity factors f1 and f2 that provide single values for comparing profiles. Comparing dissolution profiles is important for evaluating drug release and bioequivalence of pharmaceutical formulations.
This document discusses dissolution profiles and specifications. It describes different types of drug release and provides guidance on generating dissolution profiles for immediate release, delayed release, and extended release products. Key steps include following the FDA dissolution method database, using the same apparatus and conditions as the reference listed drug, and demonstrating stability in various pH conditions. It also addresses alcohol-induced dose dumping tests in various ethanol concentrations. Specifications are typically based on achieving at least 85% dissolution by certain time points.
Basic Approach to Dissolution Method Development ā Challenges and Regulatory ...Dr. Harshal Pawar
Ā
This presentation explains the theoretical as well as practical aspects of dissolution. It provides a systematic and scientific path for development of dissolution method for a new pharmaceutical product.
Dissolution as one of the most important aspects of Pharmaceutical dosage form showing the correlation between the in-vitro & in-vivo availability. Importance of dissolution, comparison with Disintegration, Sampling point, acceptance criteria as per Pharmacopoeias.
Introduction to Dissolution equipment's, Calibration of dissolution apparatus, Dissolution procedure development and validation, Dissolution method development for generic drug products.
selection of dissolution medium And dissolution study of solid dosage formAshwin Patil
Ā
The document discusses dissolution testing of solid oral dosage forms. It covers selection of dissolution media based on factors like drug solubility and formulation type. Common dissolution media include simulated gastric fluid, water and simulated intestinal fluid. Selection of parameters like rpm, time and apparatus depends on the formulation. Dissolution testing is important for quality control and bioequivalence studies. It provides insight into in vivo performance and helps product development.
A Primer on Hard Gelatin Capsule ManufacturingVivek Sinha
Ā
This document provides an overview of the process for manufacturing hard gelatin capsules. It discusses the key raw materials used, including bovine gelatin and food colors. The manufacturing process involves preparing a gelatin mucilage solution, dipping pin bars in the solution to form capsule shells, drying the shells, cutting and joining them, and performing quality checks. The capsules then undergo printing and packaging, with quality testing of raw materials, in-process materials, and finished products. Specifications are provided for testing various attributes of the hard gelatin capsule shells.
Dissolution Test development in regard to bioequivalenceanezlin
Ā
The document discusses the development and use of dissolution tests in assessing bioequivalence. It describes the Biopharmaceutics Classification System which categorizes drugs based on their solubility and permeability properties. Dissolution tests are used to evaluate product quality, ensure batch-to-batch consistency, and demonstrate similarity between formulations to support biowaivers. The key factors that influence dissolution testing are discussed, including test conditions, similarity calculations, and criteria for determining equivalent dissolution profiles. Montelukast sodium, a drug with low solubility, is presented as a case study.
This document discusses analytical method validation. It provides definitions and guidelines for validating analytical methods from regulatory agencies. Key aspects of method validation discussed include accuracy, precision, specificity, range, linearity, limits of detection and quantification. Validation parameters are described for different types of analytical tests including identification, quantitative impurity tests and assays. Guidelines are provided for qualifying analytical instrumentation and categorizing instruments based on complexity.
The document discusses biorelevant dissolution media, which aims to simulate conditions in the gastrointestinal tract in vitro in order to predict in vivo drug performance. It notes the development of biorelevant media was necessary because compendial media did not adequately simulate in vivo dissolution. The summary discusses key points about biorelevant media simulating conditions in the stomach, small intestine, and colon. It also mentions factors considered in developing biorelevant media like fluid composition, hydrodynamics, drug properties, and their use in predicting plasma profiles and developing IVIVCs.
This document summarizes USP dissolution testing apparatus and procedures. It describes 7 different apparatus for testing dissolution of solid oral dosage forms including baskets, paddles, cylinders and flow-through cells. Key steps are outlined for each apparatus, including preparation of the dosage form sample, equilibrating the dissolution medium, operating conditions, sampling time points and procedures. Temperatures and rotations speeds are specified. The goal is to perform dissolution testing under standardized and reproducible conditions to evaluate drug release characteristics.
This presentation summarizes recommendations from an ISPE working group for assessing blend and content uniformity. The group proposed modifications to address issues with the withdrawn 2002 FDA guidance. Key recommendations include a two-stage blend testing approach using statistical analysis and flexibility in selecting sampling plans, acceptance criteria, and confidence/coverage levels using a risk-based approach.
Dissolution and In Vitro In Vivo Correlation (IVIVC)Jaspreet Guraya
Ā
This presentation gives a bird's eye view on Dissolution in context with IVIVC. It discusses various levels of Correlations currently in practice. IVIVC are explained in light of biowaivers It also touches upon IVIVR, IVIVM etc.
The document discusses comparison of dissolution profiles through different methods and establishing an IVIVC (in vitro-in vivo correlation). It provides definitions of dissolution profile and objectives of comparing profiles. Various methods for comparing profiles are described, including graphical, statistical, and model-dependent/independent methods. Key factors for determining similarity between dissolution profiles using statistical methods like difference factor and similarity factor are outlined. The importance of developing an IVIVC to reduce costs and the need for bioavailability studies is also mentioned. A research article comparing different brands of metformin tablets using tests like dissolution rate, drug content and disintegration is briefly summarized.
The document discusses the validation of liquid oral dosage forms. It defines validation and its objectives, which include ensuring consistency and reproducibility of the manufacturing process. The key stages of validation are described - pre-validation qualification, process validation, and validation maintenance. For liquid orals, the validation would include equipment, raw materials, the manufacturing process, microbiological quality, product specifications, stability, and packaging. Critical process parameters are identified and acceptance criteria defined. The validation report and requirements for revalidation with changes are also summarized.
This document discusses validation of analytical procedures. It is divided into two parts. Part I provides definitions and discusses typical validation characteristics such as accuracy, precision, specificity, detection limit, and quantitation limit. Part II provides more detailed methodology guidance on how to validate these characteristics. It describes how to validate specificity, accuracy, precision, detection limit, quantitation limit, linearity, range, and robustness of analytical procedures. The goal of validation is to demonstrate that analytical procedures are suitable for their intended purpose in identifying, quantifying, and testing impurities in drug substances and products.
This document discusses considerations for developing assay methods. It recommends starting with existing reference standard methods and literature. The method should separate the analyte peak from all impurities and degradants. Tools to reduce run time include shorter columns, larger particle sizes, and optimizing mobile phase composition. The same method can sometimes be used for assay and reference standards if linearity criteria are met. Extraction efficiency must be over 150% and placebo interference under 2%. Runtimes for in-process tests should be under 5 minutes. Sample quantity for content uniformity tests is 1-3 unit doses and for assays is 3-10 unit doses.
Setting Specification Limits for Impurities in Active Pharmaceutical Ingredient (APIās).
Setting Specification Limits for Impurities in Active Pharmaceutical Ingredient (APIās)
Setting Specification Limits for Impurities in Active Pharmaceutical Ingredient (APIās)
In this presentation from CPhi 2014, Elise Gallais outlines the guidelines for cleaning validation: and focuses on analytical methods and their validation.
Cleaning validation ppt by rahul sagar, m. pharm, bbau lucknowBrajesh Kumar
Ā
This presentation discusses cleaning validation guidelines from the FDA and techniques for validating cleaning of equipment. It provides an introduction to cleaning validation, outlines FDA regulatory guidelines requiring equipment be clean prior to use, and describes types of contamination including cross-contamination with active ingredients and microbiological contamination. Validation techniques covered include swab sampling, surface rinsing, RODAC plating, Limulus amoebocyte lysate testing, and ATP bioluminescence. Acceptance criteria for cleaning validation include limits on carryover of product residues to follow-on batches.
This document discusses dissolution profiles and specifications. It describes different types of drug release and provides guidance on generating dissolution profiles for immediate release, delayed release, and extended release products. Key steps include following the FDA dissolution method database, using the same apparatus and conditions as the reference listed drug, and demonstrating stability in various pH conditions. It also addresses alcohol-induced dose dumping tests in various ethanol concentrations. Specifications are typically based on achieving at least 85% dissolution by certain time points.
Basic Approach to Dissolution Method Development ā Challenges and Regulatory ...Dr. Harshal Pawar
Ā
This presentation explains the theoretical as well as practical aspects of dissolution. It provides a systematic and scientific path for development of dissolution method for a new pharmaceutical product.
Dissolution as one of the most important aspects of Pharmaceutical dosage form showing the correlation between the in-vitro & in-vivo availability. Importance of dissolution, comparison with Disintegration, Sampling point, acceptance criteria as per Pharmacopoeias.
Introduction to Dissolution equipment's, Calibration of dissolution apparatus, Dissolution procedure development and validation, Dissolution method development for generic drug products.
selection of dissolution medium And dissolution study of solid dosage formAshwin Patil
Ā
The document discusses dissolution testing of solid oral dosage forms. It covers selection of dissolution media based on factors like drug solubility and formulation type. Common dissolution media include simulated gastric fluid, water and simulated intestinal fluid. Selection of parameters like rpm, time and apparatus depends on the formulation. Dissolution testing is important for quality control and bioequivalence studies. It provides insight into in vivo performance and helps product development.
A Primer on Hard Gelatin Capsule ManufacturingVivek Sinha
Ā
This document provides an overview of the process for manufacturing hard gelatin capsules. It discusses the key raw materials used, including bovine gelatin and food colors. The manufacturing process involves preparing a gelatin mucilage solution, dipping pin bars in the solution to form capsule shells, drying the shells, cutting and joining them, and performing quality checks. The capsules then undergo printing and packaging, with quality testing of raw materials, in-process materials, and finished products. Specifications are provided for testing various attributes of the hard gelatin capsule shells.
Dissolution Test development in regard to bioequivalenceanezlin
Ā
The document discusses the development and use of dissolution tests in assessing bioequivalence. It describes the Biopharmaceutics Classification System which categorizes drugs based on their solubility and permeability properties. Dissolution tests are used to evaluate product quality, ensure batch-to-batch consistency, and demonstrate similarity between formulations to support biowaivers. The key factors that influence dissolution testing are discussed, including test conditions, similarity calculations, and criteria for determining equivalent dissolution profiles. Montelukast sodium, a drug with low solubility, is presented as a case study.
This document discusses analytical method validation. It provides definitions and guidelines for validating analytical methods from regulatory agencies. Key aspects of method validation discussed include accuracy, precision, specificity, range, linearity, limits of detection and quantification. Validation parameters are described for different types of analytical tests including identification, quantitative impurity tests and assays. Guidelines are provided for qualifying analytical instrumentation and categorizing instruments based on complexity.
The document discusses biorelevant dissolution media, which aims to simulate conditions in the gastrointestinal tract in vitro in order to predict in vivo drug performance. It notes the development of biorelevant media was necessary because compendial media did not adequately simulate in vivo dissolution. The summary discusses key points about biorelevant media simulating conditions in the stomach, small intestine, and colon. It also mentions factors considered in developing biorelevant media like fluid composition, hydrodynamics, drug properties, and their use in predicting plasma profiles and developing IVIVCs.
This document summarizes USP dissolution testing apparatus and procedures. It describes 7 different apparatus for testing dissolution of solid oral dosage forms including baskets, paddles, cylinders and flow-through cells. Key steps are outlined for each apparatus, including preparation of the dosage form sample, equilibrating the dissolution medium, operating conditions, sampling time points and procedures. Temperatures and rotations speeds are specified. The goal is to perform dissolution testing under standardized and reproducible conditions to evaluate drug release characteristics.
This presentation summarizes recommendations from an ISPE working group for assessing blend and content uniformity. The group proposed modifications to address issues with the withdrawn 2002 FDA guidance. Key recommendations include a two-stage blend testing approach using statistical analysis and flexibility in selecting sampling plans, acceptance criteria, and confidence/coverage levels using a risk-based approach.
Dissolution and In Vitro In Vivo Correlation (IVIVC)Jaspreet Guraya
Ā
This presentation gives a bird's eye view on Dissolution in context with IVIVC. It discusses various levels of Correlations currently in practice. IVIVC are explained in light of biowaivers It also touches upon IVIVR, IVIVM etc.
The document discusses comparison of dissolution profiles through different methods and establishing an IVIVC (in vitro-in vivo correlation). It provides definitions of dissolution profile and objectives of comparing profiles. Various methods for comparing profiles are described, including graphical, statistical, and model-dependent/independent methods. Key factors for determining similarity between dissolution profiles using statistical methods like difference factor and similarity factor are outlined. The importance of developing an IVIVC to reduce costs and the need for bioavailability studies is also mentioned. A research article comparing different brands of metformin tablets using tests like dissolution rate, drug content and disintegration is briefly summarized.
The document discusses the validation of liquid oral dosage forms. It defines validation and its objectives, which include ensuring consistency and reproducibility of the manufacturing process. The key stages of validation are described - pre-validation qualification, process validation, and validation maintenance. For liquid orals, the validation would include equipment, raw materials, the manufacturing process, microbiological quality, product specifications, stability, and packaging. Critical process parameters are identified and acceptance criteria defined. The validation report and requirements for revalidation with changes are also summarized.
This document discusses validation of analytical procedures. It is divided into two parts. Part I provides definitions and discusses typical validation characteristics such as accuracy, precision, specificity, detection limit, and quantitation limit. Part II provides more detailed methodology guidance on how to validate these characteristics. It describes how to validate specificity, accuracy, precision, detection limit, quantitation limit, linearity, range, and robustness of analytical procedures. The goal of validation is to demonstrate that analytical procedures are suitable for their intended purpose in identifying, quantifying, and testing impurities in drug substances and products.
This document discusses considerations for developing assay methods. It recommends starting with existing reference standard methods and literature. The method should separate the analyte peak from all impurities and degradants. Tools to reduce run time include shorter columns, larger particle sizes, and optimizing mobile phase composition. The same method can sometimes be used for assay and reference standards if linearity criteria are met. Extraction efficiency must be over 150% and placebo interference under 2%. Runtimes for in-process tests should be under 5 minutes. Sample quantity for content uniformity tests is 1-3 unit doses and for assays is 3-10 unit doses.
Setting Specification Limits for Impurities in Active Pharmaceutical Ingredient (APIās).
Setting Specification Limits for Impurities in Active Pharmaceutical Ingredient (APIās)
Setting Specification Limits for Impurities in Active Pharmaceutical Ingredient (APIās)
In this presentation from CPhi 2014, Elise Gallais outlines the guidelines for cleaning validation: and focuses on analytical methods and their validation.
Cleaning validation ppt by rahul sagar, m. pharm, bbau lucknowBrajesh Kumar
Ā
This presentation discusses cleaning validation guidelines from the FDA and techniques for validating cleaning of equipment. It provides an introduction to cleaning validation, outlines FDA regulatory guidelines requiring equipment be clean prior to use, and describes types of contamination including cross-contamination with active ingredients and microbiological contamination. Validation techniques covered include swab sampling, surface rinsing, RODAC plating, Limulus amoebocyte lysate testing, and ATP bioluminescence. Acceptance criteria for cleaning validation include limits on carryover of product residues to follow-on batches.
This presentation discusses biowaivers, which allow waiver of in vivo bioavailability and bioequivalence studies. It covers:
- What a biowaiver means and the need for developing alternatives to in vivo studies.
- The Biopharmaceutics Classification System (BCS), which divides drugs into four classes based on solubility and permeability properties. Biowaivers can be granted for BCS Class 1 drugs with high solubility and permeability.
- The criteria for biowaivers based on the BCS, including rapid dissolution requirements and tests to demonstrate high solubility and permeability. Biowaivers can significantly reduce costs compared to conducting in vivo studies.
Dissolution testing conventional and controlled release productsMd Fiaz
Ā
Dissolution testing is important for quality control and predicting in vivo performance of drug products. It quantifies the rate and amount of drug released from solid oral dosage forms under standardized conditions. Key factors in designing a dissolution test include the apparatus, media, and acceptance criteria. The most common apparatuses are USP Type I (baskets), Type II (paddles), and Type IV (flow-through cells). Media include water, buffers, and simulated gastric/intestinal fluids. Acceptance criteria ensure a minimum percentage of drug dissolves within a specified time for quality batches. Dissolution testing is critical for developing and evaluating conventional and controlled-release drug products.
Cleaning validation is an important process in the pharmaceutical industry to ensure product safety and purity. It involves documenting evidence that an approved cleaning procedure will adequately clean equipment used in pharmaceutical production. The cleaning validation process includes planning, execution, analytical testing, and reporting phases. A cross-functional team plans the validation program, which involves grouping products, equipment, cleaning agents, and methods. Sampling techniques like swab and rinse sampling are used in the execution phase. Acceptance criteria are established and analytical tests are performed on samples to verify cleaning levels. A validation report documents the results and conclusions to obtain approval. Revalidation may be required if any changes are made to the cleaning process.
This document discusses cleaning validation which is important to prevent contamination that could affect product safety and quality. It outlines the purpose, importance and levels of cleaning validation. Key aspects covered include developing a master validation plan, defining appropriate cleaning procedures and sampling methods, establishing acceptance criteria, and using validated analytical methods. The conclusion emphasizes that cleaning procedures must be validated to ensure they are reliable and reproducible.
This document discusses the validation of dissolution test apparatus. It begins with a brief history of validation and reasons for validating equipment. Validation ensures equipment operates consistently and accurately. The document then discusses various types of dissolution test apparatus and the qualification process, including design, installation, operational, and performance qualification. It also addresses sources of error and concludes that acceptable qualification demonstrates the apparatus is validated for use in dissolution testing.
The document discusses key aspects of cleaning validation including:
1. Cleaning validation is defined as the process of removing contaminants from equipment and monitoring equipment cleanliness for subsequent manufacturing.
2. The purpose of cleaning validation is to ensure product integrity, prevent cross contamination, and allow for equipment reuse in compliance with regulations.
3. Critical parameters that impact cleaning include cleaning agents, methods, times, temperatures, and establishing worst case scenarios for validation.
This document discusses cleaning validation, which provides documented evidence that approved cleaning procedures will produce equipment suitable for processing pharmaceutical products. It defines different levels of cleaning validation based on risk. Key aspects covered include cleaning techniques, establishing acceptance criteria, sampling methods, analytical methods, and documentation requirements. The goal of cleaning validation is to achieve an appropriate level of cleanliness to avoid contamination between product batches.
Bioavailability and Bioequivalence Studies (BABE) & Concept of BiowaiversJaspreet Guraya
Ā
The presentation gives an insight on BABE studies, mathematical and statistical procedures involved in designing these studies, the official guidelines regarding study design. In the later part it also discusses about biowaivers and their role.
Dissolution, factors affecting drug dissolution, methods to evaluate dissolution, advantages and disadvantages, recent approaches--these are the topics covered in this presentation.
This document provides information about purchasing a 3Com 7030-10136 software license from Launch 3 Telecom. It describes the product, payment and shipping options, warranty, and additional services offered by Launch 3 such as repairs, maintenance contracts, equipment de-installation and recycling. Customers can purchase the license by phone, email or by clicking a link to send a request for quote.
This document provides instructions for an activity to help users identify their ideal place to live. It explains that users will view and rate images from 5 categories - natural disasters, landscapes, free time, food, and transport - on a scale from 5 to 1, with 5 being the most desirable. Users must fill out a provided activity table with their ratings. The results will then reveal which location was the user's highest rated based on the categories, with examples being provided for the United Arab Emirates, Norway, Maresme, the Caribbean, and Thailand.
O anonimato de 1438 maƧons do Grande Oriente Lusitano foi colocado em causa apĆ³s divulgaĆ§Ć£o de uma lista com seus nomes verdadeiros na internet. A lista expƵe polĆticos, banqueiros, juĆzes e jornalistas membros da maior obediĆŖncia maĆ§Ć³nica portuguesa. O antigo grĆ£o-mestre considerou a divulgaĆ§Ć£o "muito preocupante" e admitiu uma intrusĆ£o no sistema informĆ”tico da obediĆŖncia.
This document discusses the development and validation of dissolution procedures. It describes key components that must be developed, including the dissolution medium, apparatus, study design, and analytical assay method. The document provides guidance on selecting an appropriate medium based on drug properties and dosage form. It also discusses qualification of the dissolution apparatus and parameters such as rotation speed. Validation parameters that must be evaluated include specificity, linearity, range, accuracy, precision, and robustness. Developing and validating a dissolution procedure is an important but challenging process that requires consideration of multiple factors.
BCS Guideline for solubility and Dissolution.pptxImdad H. Mukeri
Ā
Briefly explanation of The Biopharmaceutics Classification System (BCS) of drug substance
and its solubility in the pH range of 1ā7.5, absorption or intestinal membrane permeability
Dissolution method and ivivc by ranjeet singhRanjeet Singh
Ā
The document discusses dissolution testing methods for oral drug formulations. It describes dissolution as a mass transfer process involving interactions at solute-solute, solute-solvent, and solvent-solvent interfaces. Official dissolution testing methods specified by regulatory agencies include the rotating basket, paddle, flow-through, reciprocating cylinder, paddle over disk, rotating cylinder, and reciprocating disk methods. Non-official methods described for specific dosage forms include the rotating bottle method for sustained release formulations and dialysis systems for poorly soluble drugs. The document also discusses the importance of establishing in vitro-in vivo correlations to ensure batch uniformity and aid new drug development.
The document discusses guidelines for stability testing of pharmaceutical products. It defines stability testing as evaluating how environmental factors affect a drug substance or product's properties over time. This helps determine shelf life, proper storage conditions, and labeling instructions. Stability testing evaluates many factors like active ingredient stability, excipient interactions, manufacturing process, dosage form, and storage conditions. It also considers degradation reactions and how they are impacted by conditions. Stability testing parameters and timepoints are described for various dosage forms like tablets, capsules, solutions, injections etc. The document also discusses ICH guidelines for stability testing and recommendations for climatic zones III and IV.
This presentation gives brief idea about types of inhalation devices, types of DPIs devices, QbD elements, bioequivalence requirement in USA and EU, and marketed DPI products.
This document discusses dissolution testing techniques used in the pharmaceutical industry. It begins with introductions to dissolution testing, including its history and importance. It then covers development of dissolution methods, including characterizing drug substances and formulations, classifying drugs based on solubility and permeability, and selecting test conditions like apparatus, medium, agitation, and time points. The document discusses compendial and regulatory expectations for dissolution testing as well as validating dissolution methods.
Formulation and evaluation of TDDS sheets.pptxomkarmandlik678
Ā
Shweta Rokade presented on formulation and evaluation of transdermal drug delivery systems (TDDS). TDDS, also known as patches, are designed to deliver drugs across the skin. The basic components of TDDS include a polymer matrix containing the drug, permeation enhancers, pressure sensitive adhesives, backing laminates and release liners. Drugs suitable for TDDS have specific properties like extensive first-pass metabolism. TDDS were evaluated through physicochemical tests, in vitro studies of drug release and skin permeation, and in vivo studies using animal and human models.
This document discusses biowaiver consideration based on the Biopharmaceutics Classification System (BCS). It provides an introduction to biowaivers and outlines the four classes in the BCS. The key requirements for a BCS-based biowaiver are described, including demonstrating high solubility, high permeability, and rapid dissolution of the drug product. The types of data needed to support a biowaiver request are summarized. Additional factors like excipients, prodrugs, and exceptions are also covered.
Dissolution testing is an important quality control tool for assessing drug release from solid oral dosage forms. Key factors that influence dissolution include solubility, permeability, dissolution rate, and drug release kinetics. The document discusses the importance of dissolution testing and outlines various parameters to consider like sink conditions, selection of media, rpm, and apparatus type. It also covers topics like intrinsic dissolution, biowaiver requests, and dissolution testing for modified release formulations. Overall, the document provides a comprehensive overview of the dissolution testing process and parameters.
The document discusses factors that influence drug product performance in in-vitro dissolution testing. It describes four main categories of factors: drug substance properties like solubility and polymorphism, formulation components like disintegrants and surfactants, manufacturing processes, and test parameters like apparatus and medium. The key purposes of in-vitro dissolution testing are product development to guide formulation selection and stability testing to ensure quality over the shelf life.
Dissolution testing measures the percentage of active pharmaceutical ingredient (API) released from solid oral dosage forms like tablets and capsules over time under controlled conditions. It is important for developing formulations, setting specifications, comparing batch quality, and evaluating post-approval changes. The test involves measuring API dissolved in different media like pH 1.2, 4.5 and 6.8 buffers using validated analytical methods. Dissolution profiles are compared using f2 calculations or by ensuring 85% dissolution within 15 minutes to determine similarity. Comparative dissolution data should be reported with purpose, conditions, results and conclusion.
The document discusses invitro dissolution testing of drugs. It defines dissolution rate and invitro dissolution tests as tests used to measure the rate and extent of dissolution of a drug from its formulation under specified conditions. Key factors in designing dissolution tests include the apparatus used, dissolution medium properties, and process parameters. Common apparatuses include basket, paddle, reciprocating cylinder, and flow-through cell methods. Dissolution testing provides important information on a drug's in vivo performance and quality control.
The document discusses drug product performance evaluation through in vitro dissolution testing. It provides details on factors that influence drug dissolution like drug substance properties, formulation composition, manufacturing process, and dissolution test conditions. The key goals of in vitro drug product testing are to characterize drug potency and release rate from oral dosage forms, provide information for formulation development, and ensure quality, comparability and stability over time. Common tests include disintegration testing and dissolution testing using apparatus specified in pharmacopeias to simulate gastrointestinal conditions. The results of in vitro testing aid product development and assessment of shelf-life and quality.
This document provides objectives and content for a chapter on tablet dosage forms. It begins by listing 7 learning objectives for students related to different tablet types, ingredients, and modified release forms. It then covers various topics on tablet dosage forms including definitions of immediate and modified release tablets, important ingredients like fillers, binders, and disintegrants, factors that influence powder compaction, and mechanisms of drug release from tablets. The document aims to educate students on the development, formulation, and performance of oral tablet dosage forms.
This document discusses dissolution, which is the process by which a solid substance solubilizes in a solvent. It defines dissolution rate and introduces the Noyes-Whitney equation. It then describes 7 types of dissolution apparatus used in compendial methods for testing drug dissolution, including rotating basket, paddle, reciprocating cylinder, and flow through cell. Key factors that affect dissolution rate are also outlined, such as drug properties, formulation components, processing methods, apparatus parameters, and test conditions.
Sample preparation techniques of solid dosage formsSathish Vemula
Ā
Knife mills and blenders are particle size reduction techniques that can be used to disperse solid dosage forms like non-disintegrating tablets for analysis. Mechanical techniques like grinding with a mortar and pestle or milling in a ball mill are commonly used to reduce the particle size and facilitate extraction of drugs from solid oral dosage forms. Agitation techniques like shaking, stirring, vortexing, and sonication are then used to further facilitate dispersion and mixing during sample preparation. The selection of appropriate particle size reduction and agitation techniques depends on the properties of the specific drug product and dosage form being analyzed.
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Development of dissolution proceduers
1. THE DISSOLUTION PROCEDURE
DEVELOPMENT AND
VALIDATION
According to general chapter # 1092 in US Pharmacopiea
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2. Sources for the dissolution methods before
going on with the UP general chapter
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3. If the case is to develop a
new dissolution method
Go to the USP guide line
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4. Purpose
ā¢ Covering items to consider for developing and validating dissolution
procedures and the accompanying analytical procedures
ā¢ It addresses the use of automation throughout the test and provides
guidance and criteria for validation
ā¢ It also addresses the treatment of the data generated and the
interpretation of acceptance criteria for immediate and modified
release solid oral dosage forms.
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7. PRELIMINARY ASSESSMENT
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ā¢ Performing Filter Compatibility
ā¢ Determining Solubility and Stability of Drug Substance in Various
Media
ā¢ Choosing a Medium and Volume
ā¢ Choosing an Apparatus
8. Performing Filter Compatibility
ā¢ Filtration is a key sample preparation step in achieving accurate test results
ā¢ The purpose of filtration is to remove undissolved drug and excipients from the
withdrawn solution. If not removed from the sample solution, particles of the
drug will continue to dissolve and can bias the results. Therefore, filtering the
dissolution samples is usually necessary and should be done immediately.
ā¢ Examples of filters used in dissolution testing can be cannula filters, filter disks or
frits, filter tips, or syringe filters.
ā¢ Adsorption of the drug(s) by the filter may occur and needs to be evaluated. Filter
materials will interact with dissolution media to affect the recovery of the
individual solutes and must be considered on a case by case basis.
ā¢ Percentage of drug loss from the filtrate due to binding may be dependent on the
drug concentration. Therefore the adsorptive interference should be evaluated
on sample solutions at different concentrations bracketing the expected
concentration range.
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9. Performing Filter Compatibility
ā¢ Where the drug adsorption is saturable, discarding an initial volume of filtrate
may allow the collection of a subsequent solution that approaches the original
solution concentration
ā¢ Prewetting of the filter with the medium may be necessary
ā¢ The filter size should be based on the volume to be withdrawn and the amount of
particles to be separated. Use of the correct filter dimensions will improve
throughput and recovery, and also reduce clogging.
ā¢ Use of a large filter for small volume filtration can lead to loss of sample through
holdup volume, whereas filtration through small filter sizes needs higher
pressures and longer times, and the filters can clog quickly.
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10. Determining Solubility and Stability of Drug
Substance in Various Media
ā¢ Solubility of the drug substance is usually evaluated by determining the
saturation concentration of the drug in different media at 37Ā° using the shake
flask solubility method (equilibrium solubility)
ā¢ Typical media for dissolution may include the following (not listed in order of
preference): diluted hydrochloric acid, buffers (phosphate or acetate) in the
physiologic pH range of 1.2ā7.5, simulated gastric or intestinal fluid (with or
without enzymes), and water
ā¢ The molarity of the buffers and acids used can influence the solubilizing effect,
and this factor may be evaluated
ā¢ Aqueous solutions (acidic or buffer solutions) may contain a percentage of a
surfactant [e.g., sodium dodecyl sulfate (SDS), polysorbate, or
lauryldimethylamine oxide] to enhance the solubility of the drug
ā¢ the surfactant concentration is above its critical micellar concentration (CMC)
ā¢ It is important to control the grade and purity of surfactants because use of
different grades could affect the solubility of the drug. For example, SDS is
available in both a technical grade and a high purity grade.
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11. Determining Solubility and Stability of Drug
Substance in Various Media
ā¢ Routinely, the dissolution medium is bufferedĶ¾ however, the use of purified
water as the dissolution medium is suitable for products with a dissolution
behavior independent of the pH of the medium. There are several reasons
why purified water may not be preferred.
ā¢ The water quality can vary depending on its source, and the
ā¢ pH of the water is not as strictly controlled as the pH of buffer solutions. Additionally,
the pH can vary from day to day and can also change during the run, depending on
the drug substance and excipients.
ā¢ Use of an aqueous organic solvent mixture as a dissolution medium is
discouragedĶ¾ however, with proper justification this type of medium may
be acceptable.
ā¢ Investigations of the stability of the drug substance should be carried out,
when needed, in the selected dissolution medium with excipients present,
at 37Ā° for sufficient time that required for completing the test.
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12. Choosing a Medium and Volume
ā¢ When developing a dissolution procedure, one goal is to have sink conditions, which are
defined as having a volume of medium at least three times the volume required to form
a saturated solution of drug substance.
ā¢ The composition and volume of dissolution medium are guided by the solubility
investigations
ā¢ The use of enzymes in the dissolution medium is permitted, when dissolution failures
occur as a result of crosslinking with gelatin capsules or gelatin coated products
ā¢ Another option is to use media that follow more closely the composition of fluids in the
stomach and intestinal tract. These media may contain physiological surface active
ingredients, such as taurocholates. The media also may contain emulsifiers (lecithin) and
components such as saline solution that increase osmolality
ā¢ antioxidants such as ascorbic acid may be used in the dissolution medium to stabilize the
drug
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13. Choosing a Medium and Volume
ā¢ For compounds that rapidly degrade to form a stable degradant,
monitoring the degradant alone or in combination with a drug
substance may be more suitable than analyzing only the drug
substance. In situ spectroscopic techniques tend to be less affected
by degradation when compared with HPLC analysis
ā¢ For compendial Apparatus 1 (basket) and Apparatus 2 (paddle), the
volume of the dissolution medium can vary from 500 to 1000 mL.
Usually, the volume needed for the dissolution test can be
determined in order to maintain sink conditions
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14. Choosing a Medium and Volume
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16. METHOD DEVELOPMENT
ā¢ Deaeration
ā¢ Sinkers
ā¢ Agitation
ā¢ Study Design
ā¢ Time points
ā¢ Observations
ā¢ Sampling
ā¢ Data Handling
ā¢ Dissolution Procedure Assessment
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17. Deaeration
ā¢ air bubbles can act as a barrier to the dissolution process and can adversely affect
the reliability of the test results
ā¢ bubbles can causes
ā¢ particles to cling to the apparatus and vessel walls
ā¢ increase buoyancy, leading to an increase in the dissolution rate
ā¢ decrease the available surface area, leading to a decrease in the dissolution rate
ā¢ Poorly soluble drugs are most sensitive to interference from air bubblesĶ¾
therefore, deaeration may be needed when testing these types of products.
ā¢ Typical steps for deareation include heating the medium, filtering, and drawing a
vacuum for a short period of time.
ā¢ oxygen concentration below 6 mg/L has been found effective as a marker for
adequate deaeration of water for the Performance Verification Test with USP
Prednisone Tablets RS
ā¢ Media containing surfactants usually are not deaerated because the process
results in excessive foaming, and usually the effect of dissolved air on the
dissolution process is mitigated by the reduced surface tension of the medium.
Sometimes, deaerating the medium before adding surfactants can be effective.
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18. Deaeration
ā¢ To determine whether deaeration of the medium is necessary,
compare results from dissolution samples run in nondeaerated
medium and medium deaerated using a compendial technique, as
described above. If no effect of deaeration is detected, this
experiment could serve as justification that deaeration is not required
in the future.
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20. Sinkers
ā¢ Sinkers are often used to adjust the buoyancy of dosage forms that would
otherwise float during testing with Apparatus 2. When sinkers are used, a
detailed description of the sinker must be provided in the written
procedure
ā¢ For materials, use 316 stainless steel wire, typically 0.032 inch/20 gauge, or
other inert material and wind the wire around cylinders of appropriate
diameter (e.g., cork borers) for an appropriate number of turns to fit the
capsule shell type
ā¢ If the sinker is handmade, the sinker material and construction procedure
instructions should be documented (e.g., dimension, design, number of
coils)Ķ¾ if a commercial sinker is used, the vendor part number should be
reported if available.
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21. Sinkers
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Although sinkers are typically used to keep the dosage form at the bottom of the
vessel, they can also be used to keep dosage forms from sticking to the vessel (e.g.,
film coated tablets).
22. Agitation
ā¢ For immediate release capsule or tablet formulations, Apparatus 1
(baskets) at 50ā100 rpm or Apparatus 2 (paddles) at 50 or 75 rpm are used
commonly. Other agitation speeds are acceptable with appropriate
justification. Rates outside 25ā150 rpm for both the paddle and the basket
are usually not appropriate because of mixing inconsistencies that can be
generated by stirring too slow or too fast. Agitation rates between 25 and
50 rpm are generally acceptable for suspensions.
ā¢ For dosage forms that exhibit coning (mounding) under the paddle at 50
rpm, the coning can be reduced by increasing the paddle speed to 75 rpm,
thus reducing the artifact and improving the data.
ā¢ If justified, 100 rpm may be used with Apparatus 2, especially for extended
release products.
ā¢ Decreasing or increasing the apparatus rotation speed may be justified if
to achieve an invitroāinvivo correlation (IVIVC) the resulting profiles better
reflect in vivo performance, or if the method results in better
discrimination without adversely affecting method variability.
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24. Study Design
Time points
ā¢ For immediaterelease dosage forms, the duration of the dissolution
procedure is typically 30ā60 min.
ā¢ Industrial and regulatory concepts of product comparability and
performance may require additional time points, which may also be
required for product registration or approval
ā¢ Products release 85% or more of the drug substance within 15 min did not
need more time point and on the other side products typically show a
gradual increase reaching 85%ā100% at about 30ā45 min need sufficient
dissolution time points to characterize the performance.
ā¢ The f2 similarity factor may not be useful when more than 85% is dissolved
at 15 min. If the f2 similarity factor is to be used, multiple time points for
the dissolution test are required, with at least two time points with mean
percent dissolved (typically for n = 12) below 85% dissolved and only one
point above 85% for both products (16). Therefore, the addition of early
time points may be useful.
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25. Study Design
Time points
ā¢ For testing an extended release dosage form, at least three time
points are chosen, to guard against dose dumping, to define the in
vitro release profile, and to show that essentially complete release
(>80%) of the drug is achieved.
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26. Study Design
Observations
ā¢ For visual observation, proper lighting (with appropriate
consideration of photo degradation) of the vessel contents and clear
visibility in the bath are essential.
ā¢ Documenting observations by drawing sketches and taking
photographs or videos can be instructive and helpful for those who
are not able to observe the realtime dissolution test.
ā¢ It is important to record observations of all six vessels to determine if
the observation is seen in all six vessels, or just a few. If the test is
performed to assist with formulation development, provide any
unique observations to the formulator
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27. Study Design
Observations
ā¢ Examples of typical observations include
ā¢ Uneven distribution of particles throughout the vessel
ā¢ Air bubbles on the inside of the vessel or on the apparatus or dosage unit
ā¢ Dancing or spinning of the dosage unit, or the dosage unit being hit by the paddle
ā¢ Adhesion of particles to the paddle or the inside of the basket, which may be
observed upon removal of the stirring device at the end of the run
ā¢ Pellicles or analogous formations, such as transparent sacs or rubbery, swollen
masses surrounding the capsule contents
ā¢ Presence of large floating particles or chunks of the dosage unit, especially at the
surface of the media.
ā¢ Whether the dosage form lands in the vessel center or offcenter, and if offcenter,
whether it sticks there.
ā¢ Time required for the complete dissolution of the capsule shell or for tablet
disintegration.
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28. Study Design
Sampling
ā¢ use chemically inert devices
ā¢ When the agitation conditions are very slow, e.g., a 50rpm basket, care
should be taken to sample consistently in the same location in the vessel
because there may be a concentration gradientĶ¾ avoid sampling very close
to the shaft or vessel wall
ā¢ During method development, a decision should be made regarding
whether to replace the media after each time point. Replacement is not
preferred because the dosage unit may be disturbed during delivery of the
media. However, replacement may be necessary if maintaining sink
conditions is a challenge.
ā¢ With replacement, the volume used in the calculations remains the same
throughout the time points, but there is some drug substance withdrawn
with each sample that will need to be accounted for in the calculations.
ā¢ the metal surfaces may release metal ions into aqueous media. The ions
can then catalyze degradation reactions, leading to artifacts during the
analytical procedures. The surfaces of stirring elements and metal locks of
syringes may be sources of interference to accurate sampling.
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32. Data Handling
ā¢ High variability in the results can make it difficult to identify trends or effects of
formulation changes. Sample size can affect the observed variability
ā¢ One guidance defines dissolution results as highly variable if the relative standard
deviation (RSD) is more than 20% at time points of 10 min or less and more than
10% at later time points for a sample size of 12.
ā¢ Dissolution results can be evaluated as either cumulative rates or fractional rates.
Cumulative rates represent the sum of all drug dissolution that occurs during an
interval (Figure 1). Fractional rates are assessed at a specific time point or during
a portion of the total test time. Typically, the rate of release will be expressed as
either mass or percentage of label claim per unit time.
ā¢ For most compendial dissolution testing, the dissolution rate is expressed as a
percentage of the label claim dissolved at the indicated test time.
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33. Dissolution Procedure Assessment
ā¢ The dissolution procedure requires an apparatus, a dissolution medium,
and test conditions that together provide a method that is sensitive to
changes in critical quality attributes, yet sufficiently rugged and
reproducible for day to day operation.
ā¢ The method should be able to be transferred between laboratories.
ā¢ The ideal dissolution procedure will not contribute an unacceptable degree
of variability and will provide a profile with adequate points below 85%
dissolved. If 85% dissolved occurs before 15 min, then f2 comparisons may
not be appropriate.
ā¢ There are many ways to challenge the sensitivity of the method. One
option is to compare dissolution profiles of formulations that are
intentionally manufactured with meaningful variations for the most
relevant critical manufacturing variable, for example, Ā±10%ā20% change to
the ranges of these variables
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37. DISCRIMINATING ABILITY
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ā¢ The challenge for scientists working in a research and development
environment is to develop a procedure that can not only guide the
formulation development process but can also be used as a regulatory
test to detect manufacturing deviations and to ensure product
consistency at release and over the productās shelf life.
40. ANALYTICAL FINISH
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ā¢ The sample handling and analytical procedure that are used to determine
the amount of drug substance dissolved during the dissolution procedure
are termed the āanalytical finish.ā
ā¢ After the samples are withdrawn from the dissolution medium, they may
require additional processing to make them suitable for the analytical
methodology used to determine the amount released
ā¢ Centrifugation of samples is not preferred, for several reasons: dissolution
can continue to occur until the solids are removed, a concentration
gradient may form in the supernatant, and energy imparted may lead to
increased dissolution of the drug substance particles.
ā¢ Spectrophotometric determination is used often because results can be
obtained faster, the analysis is simpler, it is easier to automate, and fewer
solvents are needed. The use of direct spectrophotometric determination
typically requires confirmation of specificity.
41. ANALYTICAL FINISH
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ā¢ HPLC is preferred for a number of reasons such as providing a wide
dynamic range that reduces the need to dilute some samples while
also providing sensitivity in the analysis of dilute samples, and greater
selectivity when excipients or multiple drugs in the formulation
present a significant interference
ā¢ Using a validated analytical finish, standard solutions are typically
prepared in dissolution media and analyzed at just one concentration,
either at 100% of the dosage strength or the selected Q value
because linearity of the analytical finish has been established
ā¢ A typical media blank, standard, and sample may be analyzed in a
sequence that brackets the sample with standards and blanks,
especially at the beginning and end of the analysis
42. VALIDATION
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ā¢ Analytical Finish. Validation of the analytical finish will evaluate the
attributes, linearity and range, precision, specificity, accuracy/recovery,
robustness, and stability of the sample and standard solutions
ā¢ Validation of the dissolution step will include evaluation of precision and
robustness of the dissolution sample preparation. Validation of the
dissolution step requires the use of a well characterized dosage form (e.g.,
having tight content uniformity and uniform performance)
ā¢ The interference should not exceed 2%. Note that for extended release
products, a placebo version of the finished dosage form may be more
appropriate than blends because this placebo formulation will release the
various excipients in a manner more nearly reflecting the product than will
a simple blend of the excipients
ā¢ If the placebo interference exceeds 2%, modification of the method may be
necessary.
43. VALIDATION
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ā¢ Linearity is typically established by preparing solutions of the drug
substance, ranging in concentration from less than the lowest expected
concentration to more than the highest concentration during release. A
minimum of five concentrations is normally used
ā¢ Typically, a square of the correlation coefficient (r2 ā„ 0.98) demonstrates
linearity. In addition, the y-intercept must not be importantly different
from zero.
ā¢ Fro Accuracy test: The measured recovery is typically 95%ā105% of the
amount added
ā¢ The repeatability can be assed using a minimum of six determinations at
100% of the test concentration. A typical acceptance criterion is an RSD of
<2%. The demonstration of the repeatability for the dissolution step is
conducted by performing the dissolution step on separate units of awell
characterized dosage form or equivalent composite
44. VALIDATION
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ā¢ The intermediate precision can be sassed by typical variations to be studied
include different days, analysts, and equipment.
ā¢ Acceptance criteria for intermediate precision or for ruggedness are
predetermined. A typical acceptance criterion for ruggedness is that the
difference in the mean value for dissolution results between any two
conditions, using the same strength, does not exceed an absolute 10% at
time points with <85% dissolved and does not exceed 5% for time points
>85%. Acceptance criteria may be product specific, and other statistical
tests and limits may be used.
ā¢ For Robustness Selection of parameters to be varied depends on the
dissolution procedure and analysis type. The parameters may include
medium composition (e.g., buffer or surfactant concentration, pH,
deaeration), volume, agitation rate, sampling time, and temperature.
45. VALIDATION
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ā¢ The standard solution is stored under conditions that ensure stability. The
stability of the standard solution is analyzed over a specified period of time
(for at least the time of the entire dissolution procedure), using a freshly
prepared standard solution at each time interval for comparison. The
acceptable range for standard solution stability is influenced by the
concentration and is typically between 98% and 102% at the expected final
concentration.
ā¢ The sample solution is typically stored at room temperature. The sample is
analyzed over a specified period of time, using the original sample solution
response for comparison. The typical acceptable range for sample solution
stability may be between 98% and 102%, compared with the initial analysis
of the sample solutions. If the solution is not stable, aspects to consider
include temperature (refrigeration may be needed), light protection, and
container material (plastic or glass).