This document discusses preformulation studies that are conducted to characterize the physicochemical properties of new drug substances. It covers topics like organoleptic properties, purity, particle size and shape, solubility, and powder flow properties. The goals of preformulation are established as determining necessary physicochemical parameters, kinetic profiles, physical characteristics, and compatibility with excipients. Various methods for analyzing properties like particle size, surface area, and solubility are also summarized.
This document summarizes guidelines from the International Conference on Harmonisation (ICH) regarding stability testing of new drug substances and products. It discusses ICH guidelines Q1A(R2) through Q1F, which provide recommendations on conducting stability studies under various storage conditions to determine appropriate re-test periods and shelf lives. The guidelines specify the types of studies, including stress testing, selection of batches, container closure systems, specifications, testing frequency, and evaluation criteria. The document outlines recommended storage conditions and minimum time periods for long-term, intermediate, and accelerated stability studies to support product registrations.
Pharmaceuticals Sampling plans and techniquesAshishVerma593
Sampling plans and techniques are used to select representative samples from pharmaceutical populations for testing purposes. There are three main WHO sampling formulae: n Plan uses the square root of the population plus one, p Plan uses 0.4 times the square root of the population, and r Plan uses 1.5 times the square root of the population. These formulae are used depending on factors like uniformity and source. Finished products and packaging materials should follow standards like ISO 2859 level II. The AQL provides guidelines on acceptable defect levels based on sample size and inspection level.
SUPAC, BACPAC, Post Marketing SurveillanceMANIKANDAN V
This document discusses various guidelines related to product development and technology transfer in the pharmaceutical industry. It covers SUPAC, BACPAC, and post-marketing surveillance. SUPAC provides guidance for scale-up and post-approval changes, categorizing changes into different levels based on their potential impact. BACPAC guidance addresses post-approval changes for bulk active pharmaceutical ingredients. Post-marketing surveillance involves monitoring adverse drug events after approval to ensure ongoing safety and effectiveness.
This guidance provides recommendations for holders of animal drug applications on reporting categories for changes to conditions established in approved applications. It describes changes to manufacturing sites, scales, equipment, specifications, and processes for synthetic drug substances and intermediates. The guidance recommends reporting categories of annual reports, supplements for changes being effected in 30 days, or prior approval supplements based on the type and potential impact of changes.
Documentation in pharmaceutical industryPRANJAY PATIL
Pranjay Sadashiv Patil, a first year M.Pharm student, presented on documentation in pharmaceutical quality assurance. Documentation defines a system to minimize risks from misinterpretation or errors in oral communication. It includes specifications, test procedures, distribution records, and electronic data handling. Specifications provide parameters and limits for materials, equipment, and products. Test procedures must validate compliance to the end of shelf life. Controlled documents require approval and management of changes, while uncontrolled copies are for reference with a watermark.
NEW ERA OF DRUG PRODUCT: OPPORTUNITIES AND CHALLENGESganpat420
Abstract
Introduction
Global pharmaceutical industry
Indian pharmaceutical industry
Indian Pharmaceutical Market
Opportunities
Challenges
Conclusion
References
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 summarizes guidelines from the International Conference on Harmonisation (ICH) regarding stability testing of new drug substances and products. It discusses ICH guidelines Q1A(R2) through Q1F, which provide recommendations on conducting stability studies under various storage conditions to determine appropriate re-test periods and shelf lives. The guidelines specify the types of studies, including stress testing, selection of batches, container closure systems, specifications, testing frequency, and evaluation criteria. The document outlines recommended storage conditions and minimum time periods for long-term, intermediate, and accelerated stability studies to support product registrations.
Pharmaceuticals Sampling plans and techniquesAshishVerma593
Sampling plans and techniques are used to select representative samples from pharmaceutical populations for testing purposes. There are three main WHO sampling formulae: n Plan uses the square root of the population plus one, p Plan uses 0.4 times the square root of the population, and r Plan uses 1.5 times the square root of the population. These formulae are used depending on factors like uniformity and source. Finished products and packaging materials should follow standards like ISO 2859 level II. The AQL provides guidelines on acceptable defect levels based on sample size and inspection level.
SUPAC, BACPAC, Post Marketing SurveillanceMANIKANDAN V
This document discusses various guidelines related to product development and technology transfer in the pharmaceutical industry. It covers SUPAC, BACPAC, and post-marketing surveillance. SUPAC provides guidance for scale-up and post-approval changes, categorizing changes into different levels based on their potential impact. BACPAC guidance addresses post-approval changes for bulk active pharmaceutical ingredients. Post-marketing surveillance involves monitoring adverse drug events after approval to ensure ongoing safety and effectiveness.
This guidance provides recommendations for holders of animal drug applications on reporting categories for changes to conditions established in approved applications. It describes changes to manufacturing sites, scales, equipment, specifications, and processes for synthetic drug substances and intermediates. The guidance recommends reporting categories of annual reports, supplements for changes being effected in 30 days, or prior approval supplements based on the type and potential impact of changes.
Documentation in pharmaceutical industryPRANJAY PATIL
Pranjay Sadashiv Patil, a first year M.Pharm student, presented on documentation in pharmaceutical quality assurance. Documentation defines a system to minimize risks from misinterpretation or errors in oral communication. It includes specifications, test procedures, distribution records, and electronic data handling. Specifications provide parameters and limits for materials, equipment, and products. Test procedures must validate compliance to the end of shelf life. Controlled documents require approval and management of changes, while uncontrolled copies are for reference with a watermark.
NEW ERA OF DRUG PRODUCT: OPPORTUNITIES AND CHALLENGESganpat420
Abstract
Introduction
Global pharmaceutical industry
Indian pharmaceutical industry
Indian Pharmaceutical Market
Opportunities
Challenges
Conclusion
References
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.
The document provides an overview of pre-formulation, which involves determining the physicochemical properties of a drug substance prior to developing a dosage form. It discusses the goals of pre-formulation to formulate an efficacious dosage form with good bioavailability. The protocol involves characterizing the physical, chemical, solubility, stability and compatibility properties of the drug. Key aspects covered include polymorphism, hygroscopicity, particle size, solubility, dissolution, stability in solution and solid state, and compatibility with excipients. The information guides subsequent formulation development.
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 provides information on the International Conference on Harmonization (ICH), including:
- ICH aims to harmonize technical requirements for pharmaceutical registration across regions to ensure safety and efficacy.
- It involves regulators and industry from the EU, Japan, and USA.
- The goals are to establish common guidelines and make information available globally.
- ICH guidelines cover quality, safety, efficacy, and multidisciplinary topics for drug development and review.
- The document then focuses on specific ICH guidelines related to quality, including stability testing, analytical method validation, and impurities.
Pharmaceutical packaging serves several important purposes: protection, identification, information, containment, integrity, and stability. Packaging design must consider factors like material selection, sterility, and regulations. There are three levels of pharmaceutical packaging: primary, secondary, and tertiary. Primary packaging has direct contact with the product, while secondary and tertiary packaging provide additional protection, grouping, and handling during storage and shipping. Proper packaging is essential for medical products to maintain quality and safety throughout distribution and use.
This document defines stability testing requirements for new drug products. It outlines that three primary batches packaged in the proposed marketing container closure system should undergo long term testing at 25°C/60% RH or 30°C/65% RH, accelerated testing at 40°C/75% RH, and intermediate testing if needed. Specifications, frequency of testing, storage conditions and a post-approval stability commitment are also addressed. The purpose is to provide evidence of a drug product's quality over time under various environmental conditions and establish a shelf life.
This document provides information on current good manufacturing practices (CGMP) regulations enforced by the FDA to ensure quality in pharmaceutical manufacturing. It discusses the importance of CGMP for quality products, customer satisfaction, consistency and company reputation. The objectives are to understand regulatory requirements and minimize risks that can't be detected by final testing. The document outlines various CGMP guidelines related to facilities, equipment, personnel, documentation, batch records, quality control and more. It provides details on specific areas like premises, warehousing, water systems, waste disposal, production areas and equipment cleaning/validation.
This document outlines specifications and testing procedures for pharmaceutical products. It discusses the need to validate testing procedures before adopting them routinely. It also describes the requirements for specifications of starting materials, packaging materials, intermediate and bulk products, and finished products. Specifications should include a description of the material, reference standards, qualitative and quantitative requirements, storage conditions, and expiration dates. Periodic revision may be necessary to comply with pharmacopoeia standards.
IPQC cover the entire chain of operations from the receipt of raw material in the warehouse to the release of finished products from the warehouse for distribution and or sale. IPQC is a process where quality of a product is ensured that it meets the standard according to regulatory authority guidline.
Container closure system and issues facing modern drug packagingPrathameshSarda1
This document discusses container closure systems for drug packaging and outlines some of the key issues. It begins by defining containers and closures, describing common types of containers including well-closed, single and multi-dose, light-resistant, airtight, and aerosol containers. It also classifies and discusses materials used for containers and closures. The document then outlines several issues facing modern drug packaging, including globalization, regulations, economics, new product costs, speed to market pressures, informed consumers, and serialization requirements. It concludes by noting the document will discuss advantages and disadvantages of container closure systems.
Enteral Pharmaceutical Packaging- By Kaleem PetkarKaleem Petkar
Here you will learn about all the enteral packaging types.
This slide also includes certain packaging types with illustrative examples.
You can download my slide absolutely free.
Thanks & regards
Petkar kaleem.
Q1A(R2): STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTSBhaumik Bavishi
The document provides guidelines for submitting stability data for drug substances and drug products as part of a registration application. It outlines the objectives, scope, and general principles of stability testing. Guidelines are given for conducting long-term, accelerated, and intermediate stability studies under various storage conditions. Specifications, testing frequency, number of batches, and container closure systems are also addressed. A commitment to continuing stability studies is recommended if the available data does not cover the proposed shelf life period.
This document provides an overview of New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs). NDAs are required for new drugs and include extensive clinical trial data to prove safety and efficacy. The review process takes 12-15 years and is more expensive. ANDAs are for generic drugs and do not require new clinical trials, only proof of bioequivalence. The review process takes 1-2 years and is less expensive. Both application types provide information on chemistry, manufacturing, labeling, and clinical data in a standardized format.
ICH stands for “International Conference For Harmonization Of Technical Requirements For Pharmaceutical For Human Use” brings together the medicines regulatory authorities and pharmaceutical industry around the world.
The purpose of stability testing is to provide evidence on how the quality of a drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity & light.
The Center for Drug Evaluation and Research (CDER) is responsible for protecting and promoting public health by ensuring the safety and effectiveness of human drugs. CDER oversees new drug development and reviews marketing applications, monitors drug safety after approval, and ensures quality in manufacturing. CDER's mission is to ensure that drugs are safe and effective for their intended use through activities like reviewing new drug applications, communicating drug information to health professionals and consumers, and facilitating innovation in drug development.
Closures are devices used to seal containers like bottles and jars. They must provide an effective hermetic seal while preventing contents from escaping and external substances from entering. Common closure types include screw caps, crown caps, roll-on closures, and press-on caps. Closure quality is ensured through testing of materials, dimensions, extractables and leachables, bioburden, and sterilization validation. Proper closure selection and quality control ensures container integrity and product safety.
This document provides an overview of the ICH Q1A(R2) guideline for stability testing of new drug substances and products. The guideline defines the stability data package required for drug registration in major regions. It addresses testing timelines and conditions for long term, intermediate, and accelerated studies on at least three batches of drug substance and product. The goal is to establish a re-test period or shelf life and recommended storage conditions. Specifications must cover attributes susceptible to change that could impact quality, safety or efficacy. The guideline provides detailed recommendations for testing frequency, storage conditions, and evaluation of results.
The document discusses in-process quality control (IPQC) and final product quality control (FPQC) tests for parenteral pharmaceuticals. It defines parenterals as sterile dosage forms intended for administration other than orally to directly enter systemic circulation. The types of parenterals are described based on volume and packaging. Important IPQC tests are outlined including conductivity, pH, temperature monitoring and volume filled verification. Key FPQC tests for parenterals involve sterility testing, pyrogen testing, clarity evaluation, leakage assessment, uniformity of content and weight tests, and extractable volume determination. Methods for each test are concisely explained.
This guideline is a revised of the ICHQ1A –stability data package for new drug substance /DRUG PRODUCT .The [urpose of guideline to define stability data package that sufficient for a registration application within the 3 regions of EU ,JAPAN & USA & to maintain the quality of drug products, in relation to safety , efficacy & acceptability throughout the propose shelf life.
The document discusses preformulation and summarizes some of its key aspects. Preformulation involves determining the physicochemical properties of new drug substances to aid in developing effective dosage forms. It covers topics like organoleptic properties, purity, particle size and shape, solubilization using surfactants, and the effect of temperature, pH and co-solvents on solubility. It also mentions the importance of preformulation stability studies and considering drug characteristics for different dosage forms. The goals of preformulation are establishing parameters, kinetic profiles, physical characteristics and compatibility with excipients.
This document provides an overview of preformulation studies for developing drug formulations. It discusses the importance of studying the physical and chemical properties of drug substances alone and when combined with excipients. The summary is:
1) Preformulation studies investigate the physical and chemical properties of drugs and how they interact with excipients. This helps formulators develop stable, bioavailable drug products.
2) Key properties studied include solubility, particle size, solid state properties, and how the drug behaves under different conditions like temperature, light and pH.
3) The results of preformulation studies guide formulation development and ensure the final product has the desired quality, performance and safety.
The document provides an overview of pre-formulation, which involves determining the physicochemical properties of a drug substance prior to developing a dosage form. It discusses the goals of pre-formulation to formulate an efficacious dosage form with good bioavailability. The protocol involves characterizing the physical, chemical, solubility, stability and compatibility properties of the drug. Key aspects covered include polymorphism, hygroscopicity, particle size, solubility, dissolution, stability in solution and solid state, and compatibility with excipients. The information guides subsequent formulation development.
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 provides information on the International Conference on Harmonization (ICH), including:
- ICH aims to harmonize technical requirements for pharmaceutical registration across regions to ensure safety and efficacy.
- It involves regulators and industry from the EU, Japan, and USA.
- The goals are to establish common guidelines and make information available globally.
- ICH guidelines cover quality, safety, efficacy, and multidisciplinary topics for drug development and review.
- The document then focuses on specific ICH guidelines related to quality, including stability testing, analytical method validation, and impurities.
Pharmaceutical packaging serves several important purposes: protection, identification, information, containment, integrity, and stability. Packaging design must consider factors like material selection, sterility, and regulations. There are three levels of pharmaceutical packaging: primary, secondary, and tertiary. Primary packaging has direct contact with the product, while secondary and tertiary packaging provide additional protection, grouping, and handling during storage and shipping. Proper packaging is essential for medical products to maintain quality and safety throughout distribution and use.
This document defines stability testing requirements for new drug products. It outlines that three primary batches packaged in the proposed marketing container closure system should undergo long term testing at 25°C/60% RH or 30°C/65% RH, accelerated testing at 40°C/75% RH, and intermediate testing if needed. Specifications, frequency of testing, storage conditions and a post-approval stability commitment are also addressed. The purpose is to provide evidence of a drug product's quality over time under various environmental conditions and establish a shelf life.
This document provides information on current good manufacturing practices (CGMP) regulations enforced by the FDA to ensure quality in pharmaceutical manufacturing. It discusses the importance of CGMP for quality products, customer satisfaction, consistency and company reputation. The objectives are to understand regulatory requirements and minimize risks that can't be detected by final testing. The document outlines various CGMP guidelines related to facilities, equipment, personnel, documentation, batch records, quality control and more. It provides details on specific areas like premises, warehousing, water systems, waste disposal, production areas and equipment cleaning/validation.
This document outlines specifications and testing procedures for pharmaceutical products. It discusses the need to validate testing procedures before adopting them routinely. It also describes the requirements for specifications of starting materials, packaging materials, intermediate and bulk products, and finished products. Specifications should include a description of the material, reference standards, qualitative and quantitative requirements, storage conditions, and expiration dates. Periodic revision may be necessary to comply with pharmacopoeia standards.
IPQC cover the entire chain of operations from the receipt of raw material in the warehouse to the release of finished products from the warehouse for distribution and or sale. IPQC is a process where quality of a product is ensured that it meets the standard according to regulatory authority guidline.
Container closure system and issues facing modern drug packagingPrathameshSarda1
This document discusses container closure systems for drug packaging and outlines some of the key issues. It begins by defining containers and closures, describing common types of containers including well-closed, single and multi-dose, light-resistant, airtight, and aerosol containers. It also classifies and discusses materials used for containers and closures. The document then outlines several issues facing modern drug packaging, including globalization, regulations, economics, new product costs, speed to market pressures, informed consumers, and serialization requirements. It concludes by noting the document will discuss advantages and disadvantages of container closure systems.
Enteral Pharmaceutical Packaging- By Kaleem PetkarKaleem Petkar
Here you will learn about all the enteral packaging types.
This slide also includes certain packaging types with illustrative examples.
You can download my slide absolutely free.
Thanks & regards
Petkar kaleem.
Q1A(R2): STABILITY TESTING OF NEW DRUG SUBSTANCES AND PRODUCTSBhaumik Bavishi
The document provides guidelines for submitting stability data for drug substances and drug products as part of a registration application. It outlines the objectives, scope, and general principles of stability testing. Guidelines are given for conducting long-term, accelerated, and intermediate stability studies under various storage conditions. Specifications, testing frequency, number of batches, and container closure systems are also addressed. A commitment to continuing stability studies is recommended if the available data does not cover the proposed shelf life period.
This document provides an overview of New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs). NDAs are required for new drugs and include extensive clinical trial data to prove safety and efficacy. The review process takes 12-15 years and is more expensive. ANDAs are for generic drugs and do not require new clinical trials, only proof of bioequivalence. The review process takes 1-2 years and is less expensive. Both application types provide information on chemistry, manufacturing, labeling, and clinical data in a standardized format.
ICH stands for “International Conference For Harmonization Of Technical Requirements For Pharmaceutical For Human Use” brings together the medicines regulatory authorities and pharmaceutical industry around the world.
The purpose of stability testing is to provide evidence on how the quality of a drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity & light.
The Center for Drug Evaluation and Research (CDER) is responsible for protecting and promoting public health by ensuring the safety and effectiveness of human drugs. CDER oversees new drug development and reviews marketing applications, monitors drug safety after approval, and ensures quality in manufacturing. CDER's mission is to ensure that drugs are safe and effective for their intended use through activities like reviewing new drug applications, communicating drug information to health professionals and consumers, and facilitating innovation in drug development.
Closures are devices used to seal containers like bottles and jars. They must provide an effective hermetic seal while preventing contents from escaping and external substances from entering. Common closure types include screw caps, crown caps, roll-on closures, and press-on caps. Closure quality is ensured through testing of materials, dimensions, extractables and leachables, bioburden, and sterilization validation. Proper closure selection and quality control ensures container integrity and product safety.
This document provides an overview of the ICH Q1A(R2) guideline for stability testing of new drug substances and products. The guideline defines the stability data package required for drug registration in major regions. It addresses testing timelines and conditions for long term, intermediate, and accelerated studies on at least three batches of drug substance and product. The goal is to establish a re-test period or shelf life and recommended storage conditions. Specifications must cover attributes susceptible to change that could impact quality, safety or efficacy. The guideline provides detailed recommendations for testing frequency, storage conditions, and evaluation of results.
The document discusses in-process quality control (IPQC) and final product quality control (FPQC) tests for parenteral pharmaceuticals. It defines parenterals as sterile dosage forms intended for administration other than orally to directly enter systemic circulation. The types of parenterals are described based on volume and packaging. Important IPQC tests are outlined including conductivity, pH, temperature monitoring and volume filled verification. Key FPQC tests for parenterals involve sterility testing, pyrogen testing, clarity evaluation, leakage assessment, uniformity of content and weight tests, and extractable volume determination. Methods for each test are concisely explained.
This guideline is a revised of the ICHQ1A –stability data package for new drug substance /DRUG PRODUCT .The [urpose of guideline to define stability data package that sufficient for a registration application within the 3 regions of EU ,JAPAN & USA & to maintain the quality of drug products, in relation to safety , efficacy & acceptability throughout the propose shelf life.
The document discusses preformulation and summarizes some of its key aspects. Preformulation involves determining the physicochemical properties of new drug substances to aid in developing effective dosage forms. It covers topics like organoleptic properties, purity, particle size and shape, solubilization using surfactants, and the effect of temperature, pH and co-solvents on solubility. It also mentions the importance of preformulation stability studies and considering drug characteristics for different dosage forms. The goals of preformulation are establishing parameters, kinetic profiles, physical characteristics and compatibility with excipients.
This document provides an overview of preformulation studies for developing drug formulations. It discusses the importance of studying the physical and chemical properties of drug substances alone and when combined with excipients. The summary is:
1) Preformulation studies investigate the physical and chemical properties of drugs and how they interact with excipients. This helps formulators develop stable, bioavailable drug products.
2) Key properties studied include solubility, particle size, solid state properties, and how the drug behaves under different conditions like temperature, light and pH.
3) The results of preformulation studies guide formulation development and ensure the final product has the desired quality, performance and safety.
This document provides an overview of preformulation studies for a new drug. It discusses characterizing the physical and chemical properties of the drug molecule to develop a safe, effective, and stable dosage form. Key aspects of preformulation studies that are described include salt formation, prodrug design, polymorphism, crystallinity, hygroscopicity, particle characterization, bulk density, powder flow properties, solubility analysis, stability analysis, and drug-excipient compatibility testing. The goal of preformulation is to obtain essential information to guide formulation development and design robust evaluation of the new drug candidate.
The document discusses various physicochemical properties that should be evaluated for new drug compounds, including solubility, crystallinity, polymorphism, particle size, density, moisture content, and flow properties. Understanding these properties is important for drug development and formulation design to ensure efficacy, stability, and manufacturability of drug products. Key properties discussed include the difference between amorphous and crystalline forms, how polymorphism can impact stability and solubility, and analytical techniques for characterizing these properties.
This document discusses preformulation testing, which involves investigating the physical and chemical properties of a new drug substance alone and when combined with excipients. The overall objective is to generate information to help formulate stable and bioavailable dosage forms. Key aspects covered include organoleptic properties, purity, particle size and surface area. Common methods for analyzing these parameters, such as chromatography, microscopy, and gas adsorption, are also summarized. The goals are to provide critical data for developing optimized dosage forms that can be mass produced.
This document provides an overview of preformulation studies for intramuscular injections. It discusses various parameters studied in preformulation including organoleptic properties, particle size, shape and distribution, powder flow properties, FTIR spectroscopy, DSC, X-ray diffraction, solubility, partition coefficient, and the effect of temperature on solubility. It also describes stability studies conducted at different stages including stress testing, accelerated and long-term testing to determine shelf life and storage conditions. The testing scope for liquid injectables includes parameters like pH, clarity, assay, degradation products, and functionality of container closure systems. Finally, it discusses climatic zones for stability testing and the hygroscopic nature of some drug substances.
This document discusses micromeritic properties of powders and granulation. It defines micromeritics and explains that particle size is important for physical and pharmacological properties. Common methods to determine particle size are described, including optical microscopy, sieving, sedimentation, and particle volume measurement. Derived powder properties like porosity, packing arrangement, and densities are covered. Factors affecting powder flow properties include particle size, shape, density, and surface texture. Applications of micromeritics in drug release, absorption, stability, and dose uniformity are presented. A case study on enhancing lovastatin dissolution uses methods like angle of repose, bulk density, tapped density, Carr's index, and Hausner's ratio to analyze
Powder Technology
Particle analysis in pharmaceuticals
Determination of particle size and surface area
Large scale equipment for powders
Types of powders
The document discusses preformulation studies for a new drug. It aims to characterize the physical and chemical properties of the drug substance and determine its stability. The objectives are outlined as determining solubility, kinetics, physical characteristics and compatibility with excipients. Key areas covered include analyzing the physicochemical properties, bulk characterization, solubility and stability of the drug. Analytical techniques discussed for characterization include microscopy, thermal analysis, powder X-ray diffraction and particle size determination methods. The importance of preformulation studies to develop a stable dosage form is highlighted.
The document discusses preformulation studies for new chemical entities. It defines preformulation studies and outlines their objectives. The major areas covered in preformulation research are physical description and bulk characterization, solubility analysis, and stability analysis. Key aspects studied include identification, purity, polymorphism, hygroscopicity, and thermal effects. Analytical methods are described for characterizing solid forms, solubility, and stability.
The document provides an outline for lectures on pharmaceutical dosage form processing. It will cover general introduction to manufacturing processes, formulation assessment, analytical method development, formulation development, good manufacturing practices, and drug product stability. Key aspects of preformulation are also summarized, including characterizing organoleptic properties, purity, particle size and shape, solubilization using surfactants, and preformulation stability studies. Manufacturing processes involve transforming raw materials into finished products through various treatment, machining, and reshaping steps while ensuring quality.
This document discusses pre-formulation, which involves investigating the physical and chemical properties of a drug substance alone or combined with excipients. The goal is to develop a stable, effective dosage form. Key tests described include identifying purity, density, compressibility, hygroscopicity, particle size, solid state properties, and compatibility with excipients. Properties like solubility, partition coefficient, and stability are also important to determine for pre-formulation.
Micromeritics study in different formulation • Colloidal dispersion are characterized by
particles that are too small to be seen in the ordinary microscope. • The particles of
pharmaceutical emulsion and suspension and the “fines” of powder fall in the range of the
optical microscope. • Particles having the size of coarser powder , tablet granulation , and
granular salts fall with in the sieve range. Control of particle size and the size range of a drug
can be significantly related to its physical, chemical and pharmacological properties.
Bioavailability, and physical stability in some dosage forms can also be affected by particle
size.Micromeritics is the science and technology of small particles . The unit of particle size
most frequently used in micromeritics is micrometer, also called as a micron.
The document discusses key concepts and steps in preformulation testing. Preformulation involves investigating the physical and chemical properties of a drug substance alone and when combined with excipients. This generates useful information for formulating stable and safe dosage forms with good bioavailability. Some important properties discussed include solubility, particle size and shape, melting point, thermal analysis profile, hygroscopicity, and polymorphism potential. Determining these properties of a new drug substance is an important first step before developing drug formulations.
This document discusses preformulation, which involves studying the physical and chemical properties of a drug prior to developing a dosage form. The goals of preformulation are to establish the drug's physicochemical parameters, physical characteristics, compatibility with excipients, and provide data to support dosage form design and evaluation. The major areas of preformulation study include physical description and bulk characterization, solubility analysis, and stability analysis. Specific tests described include assessing crystallinity, polymorphism, hygroscopicity, particle size, thermal effects, and powder flow properties.
This document provides information about micromeritics, which is the science and technology of small particles. It discusses several key concepts in micromeritics including particle size, shape, density, and surface area. The document then describes several important applications of micromeritics in the pharmaceutical field related to drug release, absorption, stability, and dose uniformity. Several examples are provided to illustrate how reducing particle size can impact solubility and bioavailability. Different methods for measuring particle size distribution are also summarized, including microscopic, sieving, sedimentation, and conductivity techniques.
The document provides an overview of preformulation studies. It discusses the importance of characterizing the physical and chemical properties of new drug molecules during preformulation to aid in the development of stable dosage forms. Some of the key areas covered include drug-excipient compatibility studies, stability kinetics testing, and determining properties like solubility, partition coefficient, and polymorphism that can help dictate the suitable dosage form. The goal of preformulation is to gather necessary data to rationally develop safe and efficacious dosage forms.
This document provides a list of experiments for an industrial pharmacy lab, including preparation and evaluation of various dosage forms like tablets, capsules, injections, syrups, and creams. The first experiment is on preformulation studies of prepared granules, involving determination of properties like bulk density, tapped density, angle of repose, Carr's index, and particle size distribution. The procedures for each parameter are described. Key results from the preformulation studies are summarized.
ICH Q8, Q9, and Q10 guidelines provide a risk-based and scientific approach to pharmaceutical development and manufacturing. Q8 describes pharmaceutical development and quality by design. Q9 covers quality risk management principles. Q10 addresses pharmaceutical quality systems. The guidelines work together throughout the product lifecycle from development to commercial manufacturing and continual improvement. Their integrated implementation enhances product quality and manufacturing efficiency.
Optimization techniques are used to improve pharmaceutical formulations by systematically varying factors and measuring responses. Statistical experimental designs are important tools for optimization that involve planning experiments to determine relationships between factors and responses. Common statistical designs include factorial designs, which examine multiple factors simultaneously, and response surface designs that model those relationships to find optimal conditions. The goal of optimization is to develop the best formulation possible given restrictions, with the primary objective being to improve quality, efficacy or reduce costs rather than absolutely optimize.
The document discusses bioequivalence, which refers to two drug products having the same rate and extent of absorption. Bioequivalence can be assessed through in vivo or in vitro methods. In vivo methods involve pharmacokinetic or pharmacodynamic studies in humans. In vitro methods involve dissolution studies to assess equivalence. The criteria for determining whether in vivo or in vitro studies are needed are described, including factors like dosage form, therapeutic index, and pharmacokinetics of the drug. Biowaivers for in vitro equivalence without in vivo studies are possible under certain specified conditions.
The document provides an overview of the Code of Federal Regulations (CFR) Title 21 Parts 210 and 211, which establish the Current Good Manufacturing Practice (CGMP) regulations for the manufacturing, processing, packing, or holding of drugs. It discusses the history and purpose of the FDA and CFR. It also summarizes key aspects of Parts 210 and 211, including definitions, facility requirements, quality control responsibilities, equipment and utensil cleaning procedures, and material receipt and testing standards. The regulations are intended to ensure that drugs are safe for use and have the ingredients and strength claimed.
The document discusses the process for product registration and drug approval in the United States. All new drug products must complete a registration process with the FDA to ensure safety and efficacy. This involves submitting a New Drug Application (NDA) containing clinical and manufacturing data and information. The NDA goes through a review process by FDA teams with expertise in technical areas. The review determines if the drug is approved for marketing in the United States.
This document discusses the subject of biopharmaceutics and pharmacokinetics. The subject is being taught by Mr. Sunil. The document provides the name of the subject and instructor but no other details about the content being taught.
Transdermal drug delivery systems provide several advantages over oral administration, including maintaining consistent drug levels, avoiding first-pass metabolism, and not requiring active administration. There are two main types of patches - drug-in-adhesive patches where the drug is incorporated directly into the adhesive layer, and reservoir patches where the drug is contained separately from the adhesive. Limitations include the skin posing a barrier to larger drug molecules and low drug payloads, though these systems can still be commercially viable by maintaining drug levels over multiple days. Newer technologies like microneedles and iontophoresis aim to overcome limitations and expand the types of drugs that can be delivered transdermally.
Affinity chromatography is a method used to separate biomolecules from a mixture based on specific interactions between the molecules and a ligand attached to a chromatography matrix. It was developed in the 1930s and relies on reversible interactions like enzyme-substrate or antibody-antigen binding. The target molecule binds to the ligand while unbound molecules are washed away. Then, conditions are altered to dissociate the bound molecule from the ligand, eluting it from the column in a purified form. Affinity chromatography is widely used to purify proteins, nucleic acids, and other biomolecules.
Healthy Eating Habits:
Understanding Nutrition Labels: Teaches how to read and interpret food labels, focusing on serving sizes, calorie intake, and nutrients to limit or include.
Tips for Healthy Eating: Offers practical advice such as incorporating a variety of foods, practicing moderation, staying hydrated, and eating mindfully.
Benefits of Regular Exercise:
Physical Benefits: Discusses how exercise aids in weight management, muscle and bone health, cardiovascular health, and flexibility.
Mental Benefits: Explains the psychological advantages, including stress reduction, improved mood, and better sleep.
Tips for Staying Active:
Encourages consistency, variety in exercises, setting realistic goals, and finding enjoyable activities to maintain motivation.
Maintaining a Balanced Lifestyle:
Integrating Nutrition and Exercise: Suggests meal planning and incorporating physical activity into daily routines.
Monitoring Progress: Recommends tracking food intake and exercise, regular health check-ups, and provides tips for achieving balance, such as getting sufficient sleep, managing stress, and staying socially active.
Michigan HealthTech Market Map 2024. Includes 7 categories: Policy Makers, Academic Innovation Centers, Digital Health Providers, Healthcare Providers, Payers / Insurance, Device Companies, Life Science Companies, Innovation Accelerators. Developed by the Michigan-Israel Business Accelerator
PET CT beginners Guide covers some of the underrepresented topics in PET CTMiadAlsulami
This lecture briefly covers some of the underrepresented topics in Molecular imaging with cases , such as:
- Primary pleural tumors and pleural metastases.
- Distinguishing between MPM and Talc Pleurodesis.
- Urological tumors.
- The role of FDG PET in NET.
MBC Support Group for Black Women – Insights in Genetic Testing.pdfbkling
Christina Spears, breast cancer genetic counselor at the Ohio State University Comprehensive Cancer Center, joined us for the MBC Support Group for Black Women to discuss the importance of genetic testing in communities of color and answer pressing questions.
Under Pressure : Kenneth Kruk's StrategyKenneth Kruk
Kenneth Kruk's story of transforming challenges into opportunities by leading successful medical record transitions and bridging scientific knowledge gaps during COVID-19.
Stem Cell Solutions: Dr. David Greene's Path to Non-Surgical Cardiac CareDr. David Greene Arizona
Explore the groundbreaking work of Dr. David Greene, a pioneer in regenerative medicine, who is revolutionizing the field of cardiology through stem cell therapy in Arizona. This ppt delves into how Dr. Greene's innovative approach is providing non-surgical, effective treatments for heart disease, using the body's own cells to repair heart damage and improve patient outcomes. Learn about the science behind stem cell therapy, its benefits over traditional cardiac surgeries, and the promising future it holds for modern medicine. Join us as we uncover how Dr. Greene's commitment to stem cell research and therapy is setting new standards in healthcare and offering new hope to cardiac patients.
Can coffee help me lose weight? Yes, 25,422 users in the USA use it for that ...nirahealhty
The South Beach Coffee Java Diet is a variation of the popular South Beach Diet, which was developed by cardiologist Dr. Arthur Agatston. The original South Beach Diet focuses on consuming lean proteins, healthy fats, and low-glycemic index carbohydrates. The South Beach Coffee Java Diet adds the element of coffee, specifically caffeine, to enhance weight loss and improve energy levels.
Feeding plate for a newborn with Cleft Palate.pptxSatvikaPrasad
A feeding plate is a prosthetic device used for newborns with a cleft palate to assist in feeding and improve nutrition intake. From a prosthodontic perspective, this plate acts as a barrier between the oral and nasal cavities, facilitating effective sucking and swallowing by providing a more normal anatomical structure. It helps to prevent milk from entering the nasal passage, thereby reducing the risk of aspiration and enhancing the infant's ability to feed efficiently. The feeding plate also aids in the development of the oral muscles and can contribute to better growth and weight gain. Its custom fabrication and proper fitting by a prosthodontist are crucial for ensuring comfort and functionality, as well as for minimizing potential complications. Early intervention with a feeding plate can significantly improve the quality of life for both the infant and the parents.
LGBTQ+ Adults: Unique Opportunities and Inclusive Approaches to CareVITASAuthor
This webinar helps clinicians understand the unique healthcare needs of the LGBTQ+ community, primarily in relation to end-of-life care. Topics include social and cultural background and challenges, healthcare disparities, advanced care planning, and strategies for reaching the community and improving quality of care.
KEY Points of Leicester travel clinic In London doc.docxNX Healthcare
In order to protect visitors' safety and wellbeing, Travel Clinic Leicester offers a wide range of travel-related health treatments, including individualized counseling and vaccines. Our team of medical experts specializes in getting people ready for international travel, with a particular emphasis on vaccines and health consultations to prevent travel-related illnesses. We provide a range of travel-related services, such as health concerns unique to a trip, prevention of malaria, and travel-related medical supplies. Our clinic is dedicated to providing top-notch care, keeping abreast of the most recent recommendations for vaccinations and travel health precautions. The goal of Travel Clinic Leicester is to keep you safe and well-rested no matter what kind of travel you choose—business, pleasure, or adventure.
About this webinar: This talk will introduce what cancer rehabilitation is, where it fits into the cancer trajectory, and who can benefit from it. In addition, the current landscape of cancer rehabilitation in Canada will be discussed and the need for advocacy to increase access to this essential component of cancer care.
Unlocking the Secrets to Safe Patient Handling.pdfLift Ability
Furthermore, the time constraints and workload in healthcare settings can make it challenging for caregivers to prioritise safe patient handling Australia practices, leading to shortcuts and increased risks.
We are one of the top Massage Spa Ajman Our highly skilled, experienced, and certified massage therapists from different corners of the world are committed to serving you with a soothing and relaxing experience. Luxuriate yourself at our spas in Sharjah and Ajman, which are indeed enriched with an ambiance of relaxation and tranquility. We could confidently claim that we are one of the most affordable Spa Ajman and Sharjah as well, where you can book the massage session of your choice for just 99 AED at any time as we are open 24 hours a day, 7 days a week.
Visit : https://massagespaajman.com/
Call : 052 987 1315
Empowering ACOs: Leveraging Quality Management Tools for MIPS and BeyondHealth Catalyst
Join us as we delve into the crucial realm of quality reporting for MSSP (Medicare Shared Savings Program) Accountable Care Organizations (ACOs).
In this session, we will explore how a robust quality management solution can empower your organization to meet regulatory requirements and improve processes for MIPS reporting and internal quality programs. Learn how our MeasureAble application enables compliance and fosters continuous improvement.
2. CONTENTS
Introduction
Organoleptic properties
Purity
Particle size, shape and surface area
Solubilisation, or solubility, Surfactants and its importance
Temperature, pH, co-solvency, solid dispersion, β-
cyclodextrin drug-dispersion system
Crystal properties and polymorphism
Compatibility studies
Preformulation stability studies
A consideration of physico-chemical characteristics of new
drug molecules with respect to different dosage forms
4/25/2023
MMCP 2
3. Preformulation
Preformulation is branch of Pharmaceutical science that
utilizes biopharmaceutical principles in the determination of
physicochemical properties of the drug substance.
Prior to the development of any dosage form new drug , it is
essential that certain fundamental physical & chemical
properties of drug powder are determined .
This information may dictate many of subsequent event &
approaches in formulation development.
This first learning phase is called as preformulation.
4/25/2023
MMCP 3
4. INTRODUCTION
DEFINITION:-
Investigation of physico-chemical properties of the
new drug compound that could affect drug
performance and development of an efficacious
dosage form”.
Preformulation commences when a newly
synthesized drug shows a sufficient pharmacologic
promise in animal model to warrant evaluation in
man.
4/25/2023
MMCP 4
5. Introduction
The preformulation is the first step in the rational
development of a dosage form of a drug substance
alone and when combined with excipients.
Objective :
To generate useful information to the
formulator to design an optimum drug delivery
system.
4/25/2023
MMCP 5
6. Introduction
Before embarking on a formal programme of
preformulation, scientist must consider the following
:
1. Available physicochemical data (including
chemical structure, different salt available).
2. Anticipated dose.
3. Supply situation and development schedule.
4. Availability of stability – indicating assay.
4/25/2023
MMCP 6
7. GOALS OF PREFORMULATION
To establish the necessary physicochemical
parameters of new drug substances.
To determine kinetic rate profile.
To establish physical characteristics.
To establish compatibility with common
excipients.
4/25/2023
MMCP 7
8. Preliminary Evaluation
a) Compound identity.
b) Formula and molecular weight.
c) Structure.
d) Therapeutic indications:
- Probable human dose.
- Desired dosage form(s)
- Bioavailability model
- Competitive products
4/25/2023
MMCP 8
11. COLOR
Color is generally a function of a drug’s inherent
chemical structure relating to a certain level of
unsaturation.
Color intensity relates to the extent of unsaturation as
well as the presence of chromophores.
Some compound may appear to have color although
structurally saturated.
4/25/2023
MMCP 11
12. ODOUR
The substance may exhibit an inherent odor
characteristic of major functional groups present.
Odor greatly affects the flavor of a preparation or
food stuff.
TASTE
If taste is considered as unpalatable, consideration is
to be given to the use of a less soluble chemical form
of the drug.
The odour and taste may be suppressed by using
appropriate flavors and excipients or by coating the
final product.
4/25/2023
MMCP 12
13. PURITY
Designed to estimate the levels of all known &
significant impurities & contaminates in the drug
substance under evaluation.
Study performed in an analytical research &
development group.
It is another parameter which allows for comparison
with subsequent batches.
Occasionally, an impurity can affect stability.
e.g.
- Metal contamination
- Appearance
4/25/2023
MMCP 13
14. PURITY
The techniques used for characterizing the purity of a
drug are the same as those used for other purpose in a
preformulation study.
Thin layer chromatography is a wide ranging
applicability & is an excellent tool for characterizing
the purity.
HPLC, paper chromatography & gas
chromatography are also useful.
More quantitative information can be obtained by
using quantitative differential scanning calorimetry.
4/25/2023
MMCP 14
15. PARTICLE SIZE
Particle size is characterized using these
terms :
i. Very coarse (#8)
ii. Coarse (#20)
iii. Moderately coarse (#40)
iv. Fine (#60)
v. Very fine (#80)
4/25/2023
MMCP 15
16. PARTICLE SIZE
Particle size can influence variety of
important factors :
- Dissolution rate
- Suspendability
- Uniform distribution
- Penetrability
- Lack of grittiness
4/25/2023
MMCP 16
18. Methods to Determine Particle Size
1. Sieving method :
Range : 50 – 150 µm
Simple, inexpensive
If powder is not dry, the apertures get clogged.
2. Microscopy :
Range : 0.2 – 100 µm
Particle size can be determined by the use of
calibrated grid background.
Most direct method.
Slow & tedious method.
4/25/2023
MMCP 18
19. Methods to Determine Particle Size
3. Sedimentation method :
Range : 1 - 200 µm
Andreasen pipette is used.
Particle size is calculated by Stoke’s law :
dst =
Where,
h = distance of fall in time, t
n = viscosity of the medium
ρs = density of the particles
ρ0 = density of the dispersion medium
g = acceleration due to gravity
4/25/2023
MMCP 19
18 η h
(ρs -ρ0) gt
20. Methods to Determine Particle Size
4. Light energy diffraction :
Range : 0.5 – 500 µm
Particle size is determined by the reduction in light
reaching the sensor as the particle, dispersed in a liquid
or gas, passes through the sensing zone.
Quick & fast.
5. Laser holography :
Range : 1.4 – 100 µm
A pulsed laser is fired through an aerosolized particle
spray & photographed in three dimensional with
holographic camera, allowing the particles to be
individually imaged & sized.
4/25/2023
MMCP 20
21. Methods to Determine Particle Size
6. Cascade impaction :
The principle that a particle driven by an
airstream will hit a surface in its path, provide
that its inertia is sufficient to overcome the drug
force that tends to keep in it in airstream.
4/25/2023
MMCP 21
22. POWDER FLOW PROPERTIES
Powder flow properties can be affected by change in particle
size, shape & density.
The flow properties depends upon following-
1. Force of friction.
2. Cohesion between one particle to another.
Fine particle posses poor flow by filling void spaces
between larger particles causing packing & densification of
particles..
By using glident we can alter the flow properties.
e.g. Starch, Talc.
4/25/2023
MMCP 22
23. Determination Of Powder Flow Properties
By determining Angle Of
Repose.
A greater angle of repose
indicate poor flow.
It should be less than 30°.
& can be determined by
following equation.
tan θ = h/r.
where, θ = angle of repose.
h=height of pile.
r= radius.
Angle Of
Repose
( In degree)
Type Of Flow
<25 Excellent
25-30 Good
30-40 Passable
>40 Very poor
4/25/2023
MMCP 23
24. Determination Of Powder Flow Properties
Measurement of free flowing powder by
compressibility.
Also known as Carr's index.
CARR’S INDEX(%) =(TAPPED DENSITY – POURED DENSITY) X 100
TAPPED DENSITY
It is simple, fast & popular method of predicting
powder flow characteristics.
4/25/2023
MMCP 24
25. Determination Of Powder Flow Properties
Carr’s Index Type of flow
5-15 Excellent
12-16 Good
18-21 Fair To Passable
23-35 Poor
33-38 Very Poor
>40 Extremely Poor
4/25/2023
MMCP 25
27. PARTICLE SHAPE
Particle shape will influence the surface area, flow of
particles, packing & compaction properties of the
particles.
A sphere has minimum surface area per unit volume.
Therefore, these properties can be compared for
spheres & asymmetric particles, in order to decide
the shape.
The following expression can be obtained:
Property Sphere particle
surface area πds
2 αs x dp
2
volume (1/6)πds
3 αv x dp
3
4/25/2023
MMCP 27
Cont…
28. PARTICLE SHAPE
Therefore,
surface area = πds
2 = αs x dp
2
Volume = (1/6)πds
3 = αv x dp
3
Solving for αs & αv by equating the appropriate properties
provides:
αs =
πds
2 & αv =
πds
3
When particle shape is spherical, the ds = dp
Thus, αs = π = 3.124 & αv = π/6 = 0.524
Therefore, Shape factor = αs = 3.124 = 6
αv 0.524
4/25/2023
MMCP 28
dp2 6 dp3
29. SURFACEAREA
Particle size & surface area are inversely related
to each other.
Smaller the drug particle, greater the surface area.
Specific surface is defined as the surface area per
unit weight (Sw) or unit volume (Sv) of the
material.
4/25/2023
MMCP 29
30. SURFACEAREA
Estimation of Sw:
Sw = Surface area = Surface area
Weight density x volume
= Sv
ρ
= 6
ρ . d
4/25/2023
MMCP 30
31. Methods for determining
surface area
1. Adsorption method :
Particles with a large specific surface are good
adsorbents for the adsorption of gases & of solutes
from solution.
The volume of nitrogen gas, Vm, in cm3 that 1 g of the
powder can adsorb when the monolayer is complete is
more accurately given by using the BET equation,
however, which can be written as:
P = 1 + (b-1) . P
V(P0 – P) Vmb Vmb P0
4/25/2023
MMCP 31
Cont….
32. Methods for determining
surface area
Where,
V = Volume of gas in cm3 adsorbed per gram of powder
at pressure P.
P = Pressure of the adsorbate, in mmHg.
Po= Saturation vapor pressure (monolayer)
Vm= Amount of vapor adsorbed per unit mass adsorbent,
when the surface is covered with monomolecular
layer
b = Constant that express the difference between the
heat of adsorption & heat of liquefaction of the
adsorbate (nitrogen).
4/25/2023
MMCP 32
34. HOWEVER SIZE REDUCTION
IS NOT REQUIRED IN FOLLOWING CASES
WHEN DRUG IS UNSTABLE.
DEGRADE IN SOLUTION FORM.
PRODUCE UNDESIRABLE EFFECTS.
WHEN SUSTAINED EFFECT IS DESIRED.
4/25/2023
MMCP 34
35. The amount of substance that passes into
solution in order to establish equilibrium at
constant temperature and pressure to
produce a saturated solution.
4/25/2023
MMCP 35
36. If solubility is <1mg/ml indicates need for salt
formation to improve solubility.
If solubility is <1mg/ml in pH= 1 to 7,
preformulation study should be initiated.
Solubility should ideally be measured at two
temperatures: 4°C and 37°C.
4°C to ensure Physical stability.
37°C to support Biopharmaceutical evaluation.
4/25/2023
MMCP 36
37. Description Parts of solvent required for
one part of solute
Very soluble < 1
Freely soluble 1 - 10
Soluble 10 - 30
Sparingly soluble 30 - 100
Slightly soluble 100 - 1000
Very slightly soluble 1000 - 10,000
Insoluble > 10,000
4/25/2023
MMCP 37
38. SOLUBILITY ANALYSIS
Preformulation solubility studies focus on drug
solvent system that could occur during the delivery of
drug candidate.
For e.g. A drug for oral administration should be
examined for solubility in media having isotonic
chloride ion concentration and acidic pH.
4/25/2023
MMCP 38
39. Analytic method that are particularly useful
for solubility measurement include HPLC, UV
spectroscopy, Fluorescence spectroscopy and
Gas chromatography.
Reverse phase HPLC offer accurate and
efficient mean of collecting solubility data of
drug.
4/25/2023
MMCP 39
SOLUBILITY ANALYSIS
40. Ionization constant (pKa)
Can be calculated by Henderson Hasselbach
equation-
For acidic drugs….pH= pKa+ log [ionized drug]
[unionized drug]
For basic drugs….pH= pKa+ log[unionized drug]
[ionized drug]
4/25/2023
MMCP 40
41. pH Solubility Profile
The solubility of acidic or basic drug will show
difference in solubility with changes in pH.
pH solubility profile of a drug can be established
by running the equilibrium solubility experiment
within pH range of 3-7.
4/25/2023
MMCP 41
42. Partition Coefficient
It is the ratio of unionized drug distributed
between organic and aqueous phase at equilibrium.
P o/w = ( C oil / C water )equilibrium
4/25/2023
MMCP 42
43. Effect Of Temperature
The heat of solution Hs, represents the heat
released or absorbed when a mole of solute is
dissolved in large quantity of solvent.
Endothermic reaction
Exothermic reaction
4/25/2023
MMCP 43
44. Determination of solubility
The following points should be considered
The solvent & solute must be pure.
A saturated solution must be obtained before any
solution is removed for analysis.
The method of separating a sample of saturated
solution from undissolved solute must be
satisfactory.
The method of analyzing solution must be reliable
Temperature must be adequately controlled .
4/25/2023
MMCP 44
45. Addition of co-solvent
pH change method
Reduction of particle size
Temperature change method
Hydotrophy
Addition of Surfactant
Dielectrical Constant
Complexation
4/25/2023
MMCP 45
General Method of Increasing
the Solubility
46. • Weak Electrolyte :- Phenobarbitone
• Non polar :- Nitro Cellulose
These are poorly soluble in given solvent.
For such poorly soluble materials, to enhance
their solubility, the water miscible solvents are used
in which the drug has good solubility.
This process of improving solubility is known as
co-solvency and the solvent used is known as co-
solvents.
4/25/2023
MMCP 46
Addition Of Co-Solvent
47. e.g. Phenobarbitone is insoluble in water. A clear
solution is obtained by dissolving in mixture of
Alcohol, Glycerin, Propylene glycol.
e.g. Cosolvents:-
PG, glycerin, sorbitol, PEG, Glyceryl formal,
glycofurol, ethyl carbamate, ethyl lactate and
dimethyl acetamide.
4/25/2023
MMCP 47
Addition Of Co-Solvent
48. pH change Method
Weak base:- Alkaloids, Local Anaesthesia
Weak acid:- Sulphonamides, Barbiturates
In aqueous medium they dissociate poorly and
undissociated portion is insoluble.
e.g. Benzoic acid, Phenobarbitone
So, solubility of the undissociated portion is
improved by pH control.
For weak acidic drug:- increase pH, solubility is
increase.
For weak base drug:- decrease pH, increase
solubility.
4/25/2023
MMCP 48
49. Reduction in Particle size improve solubility of
drug.
Basically reduction in particle size increase contact
surface area of the particle, there by ultimately it
increase rate of solubility of drug.
Reduction Of Particle size
4/25/2023
MMCP 49
50. In endothermic reaction by increasing temperature
solubilityisincrease.
In exothermic reaction by increasing temperature
solubility is decrease.
e.g. Methyl Cellulose when mixed with water and
temperature is raised, it becomes insoluble. To
dissolve it cold water is added.
4/25/2023
MMCP 50
Temperature Change Method
51. The term Hydotrophy has been used to designate the
increase in solubility in water of various substances
due to the presences of large amount of additives.
e.g. Solubilization of Benzoic acid with Sodium
benzoate.
4/25/2023
MMCP 51
Hydotrophy
52. Surfactants are molecules with well defined polar
and non-polar region that allow them to aggregate in
solution to form micelles. Non polar drugs can
partition into micelles and be solubilized.
e.g. Surfactant based solution of Taxol, that is
solubilized in 50% solution of Cremophor.
4/25/2023
MMCP 52
Addition of Surfactant
53. Dielectrical Constant is the effect that substances
has, when it acts as a solvent on the case with which it
separates oppositely charged atoms.
e.g. DEC of Water- 80
Kerosene- 2
Glycerine- 48
.2
4/25/2023
MMCP 53
Dielectrical Constant
54. Complexation
For the Complexation occur both drug and ligand
molecule should be able to donate or accept
electrons.
The solubility of compound is the sum of solubility
of the compound and its complex.
e.g. HgI2 (Mercuric Iodide) is sparingly soluble in
water. Its solubility in water is increased by forming
complex with KI.
HgI2 +2KI K2HgI4 (water soluble)
4/25/2023
MMCP 54
55. SURFACTANT
Surfactants:-
are wetting agents that lower the surface
tension of a liquid, allowing easier spreading,
and lower the interfacial tension between two
liquids.
Classification
Some commonly encountered surfactants of
each type include:
1. Ionic 2. Non ionic
Cationic
Anionic
Zwitterionic
4/25/2023
MMCP 55
56. IONIC
Cationic Surfactants:-
Quaternary ammonium salts are more preferred
because they are less affected by pH.
e.g. Cetyl Trimethyl Ammonium Bromide (CTAB)
Hexadecyl Trimethyl Ammonium Bromide, and other
Alkyltrimethyl Ammonium Salts, Cetylpyridinium
Chloride (cpc)
4/25/2023
MMCP 56
57. Anionic Surfactants:-
They are the most commonly used surfactants,
containing Carboxylate, Sulfonate, Sulfate ions.
e.g. Sodium Dodecyl Sulphate (SDS), Ammonium
Lauryl Sulphate and other alkyl sulfate salts, Sodium
Laureth Sulphate, also known as Sodium Lauryl
Ether Sulphate (SLES).
4/25/2023
MMCP 57
IONIC
58. Zwitterionic:-
When a single surfactant molecule exhibit both
anionic and cationic dissociations it is called
amphoteric or Zwitterionic.
The anion include carboxylates and phosphate
group and the cation include quaternary
ammonium group.
e.g. Dodecly Betamine
Dodecly Dimethylamine Oxide
4/25/2023
MMCP 58
IONIC
59. NONIONIC
These are most widely used because they are
free from non compatability, stability and
potential toxicity and classified as water soluble
and water insoluble non ionic surfactants.
e.g. Long chain fatty acids, fatty alcohols
Water solubility of these agents is further
increased by addition of polyoxyethylene groups
through ether linkage with one of the alcohol
group.
e.g. spans
4/25/2023
MMCP 59
61. Why Stability?
Provide a evidence on how the quality of a drug
substance or drug product varies with time under the
influence of a variety of environmental factors such
as….. temperature, Humidity and light.
Establish a re-test period for the drug substance or a
shelf life for the drug product and recommended storage
conditions.
Because physical, chemical or microbiological changes
might impact the efficiency and security of the final
product
4/25/2023
MMCP 61
62. Where and Why?
Stability Studies are preformed on ...
Drug Substances (DS) The unformulated drug
substance that may subsequently be formulated with
excipients to produce the dosage form.
Drug Products (DP) The dosage form in the final
immediate packaging intended for marketing…….
controlled and documented determination of
acceptable changes of the drug substance or drug
product
4/25/2023
MMCP 62
63. What are changes?
Physical changes
• Appearance
• Melting point
• Clarity and color of solution
• moisture
• Crystal modification (Polymorphism)
• Particle size
Chemical changes
• Increase in Degradation
• Decrease of Assay
Microbial changes
4/25/2023
MMCP 63
64. Forced degradation studies
Acidic & Basic conditions.
Dry heat exposure
UV radiation exposure
Influence of pH
Influence of temperature
Influence of ionic strength
4/25/2023
MMCP 64
65. Arrhenius Equation
K = Ae-Ea /RT
where..k = specific rate of degradation.
R = gas constant ( 1.987 calories degree -1mole)
T = absolute temperature.
A = frequency factor.
4/25/2023
MMCP 65
66. Arrhenius Equation
Plot of log K v/s 1/T….yields a slope equal to -Ea/2.303 R ….. From
which heat of activation (Ea) can be calculated.
Log k2/k1 = ΔHa/2.303 R . (T2 –T1 )/T2.T1
4/25/2023
MMCP 66
68. Testing scope for Solid dosage
Physical-chemical properties
– Appearance
– Elasticity
– Mean mass
– Moisture
– Hardness
– Disintegration
– Dissolution
Chemical properties
– Assay
– Degradation
Microbial properties
Container closure system properties
– Functionality tests (e.g. extraction from blister)
4/25/2023
MMCP 68
Tablet & Capsule
69. Testing scope for Oral liquid form
Physical-chemical properties
– pH
– Color & clarity of solution
–Viscosity
– Particle size distribution (for oral suspensions only)
Chemical properties
– Assay
– Degradation products
– Degradation preservatives
– Content antioxidants
Microbial properties
Container closure system properties
– Functionality tests
4/25/2023
MMCP 69
70. Testing scope for
LIQUID FORMS for inj. and PARENTRAL
Physical-chemical properties
– pH
– Loss on weight
– Color & clarity of solution
Chemical properties
– Assay
– Degradation products
– Degradation preservatives
– Content antioxidants
Microbial properties
Container closure system properties
– Functionality tests
4/25/2023
MMCP 70
71. Testing scope for
SEMI LIQUID FORMS
Physical-chemical properties
– Appearance, odor, homogenesity, consistency
– Loss on weight,Viscosity
– Content uniformity (within the container)
Chemical properties
– Assay
– Degradation products
– Content preservatives
– Content antioxidants
Microbial properties
Container closure system properties
– Functionality tests
4/25/2023
MMCP 71
72. Climatic Zones / Storage conditions
Climatic Zone
Countries
Calculated data
Temp. humidity
°C % r.h.
Derived data
Temp humidity
°C % r.h.
Climatic Zone I
"Temperate"
Japan, United Kingdom,
Northern Europe,
Canada, Russia, United
States
20 42 21 45
Climatic Zone II
"Mediterranean,
Subtropical"
Japan, United States,
Southern Europe
26.4 52 25 60
4/25/2023
MMCP 72
73. Climatic Zones / Storage conditions
Climatic Zone
Countries
Calculated data
Temp. humidity
°C % r.h.
Derived data
Temp humidity
°C % r.h.
Climatic Zone III
"Hot, dry"
Iran, Iraq, Sudan
26,4 35 30 35
Climatic Zone IV
"Hot, humid"
Brazil, Ghana, Indonesia,
Nicaragua,
Philippines
26,7 76
30 70
4/25/2023
MMCP 73
74. What is ICH?
ICH stands for International Conference on Harmonization
of
Technical Requirements for Registration of Pharmaceuticals for
Human use
Objectives of ICH
• Harmonization of registration applications within the three
regions of the EU, Japan and the United States.
• ICH is a joint initiative involving both regulators and industry
as equal partners in the scientific and technical discussions of
the testing procedures which are required to ensure and assess
the safety,quality and efficacy of medicines.
4/25/2023
MMCP 74
75. What or Who is ICH?
There are Six Parties directly involved in the decision making process
• EU: European Commission - European Union
• EFPIA: European Federation of Pharmaceutical Industries and
Associations
• MHLW: Ministry of Health, Labor andWelfare, Japan
• JPMA: Japan Pharmaceutical Manufacturers Association
• FDA: US Food and Drug Administration
• PhRMA: Pharmaceutical Research and Manufacturers of America
4/25/2023
MMCP 75
76. There are additionally observers installed to act as a link
with non-ICH countries and regions
• WHO
•The European FreeTrade Area (EFTA),
represented by Swissmedic Switzerland
• Health Canada
٠Global guidelines
4/25/2023
MMCP 76
77. ICH Guidelines
• QualityGuidelines “Q” (chemical and pharmaceuticalQA)
– details see next slide
• Safety Guidelines “S” (in vitro and in vivo pre-clinical studies)
– covering CarcinogenicityTesting, GenotoxicityTesting,
Toxicokinetics and Pharmacokinetics ….. etc.
• Efficacy Guidelines “E” (clinical studies in human subject)
– Covering clinical safety, Dose Response Studies, Good
Clinical Practices, Clinical evaluation …. etc.
• Multidisciplinary Guidelines “M”
– Covering MedicalTerminology, Electronic Standards for
Transmission of Regulatory Information …… etc.
– Important for Stability !
» Guideline M4:The CommonTechnical Document (CTD)
4/25/2023
MMCP 77
78. ICH Q-Guidelines (Quality)
Stability Testing in Climatic Zone I and II (Q1A)
Photostability Testing (Q1B)
Stability Testing for New Dosage Forms (Q1C)
Bracketing and Matrixing Designs (Q1D)
Evaluation of Stability Data (Q1E)
Stability Testing in Climatic Zones III and IV (Q1F)
Validation of Analytical Procedures (Q2)
Impurities (Q3)
Biotechnological Products (Q5)
Specifications (Q6)
4/25/2023
MMCP 78
79. Study Storage condition
Minimum time period
covered by data at
submission
Long term 25°C ± 2°C / 60% ± 5% r.h or
30°C ± 2°C / 65% ± 5% r.h.
12 months
Intermediate 30°C ± 2°C / 65% ± 5% r.h. 6 months
Accelerated 40°C ± 2°C / 75% ± 5% r.h. 6 months
4/25/2023
MMCP 79
Drug substances - General case
Drug substances - intended for storage in a Refrigerator
Study Storage condition Minimum time period
covered by data at
submission
Long term 5°C ± 3°C 12 months
Accelerated 25°C ± 2°C / 60% ± 5% r.h. 6 months
80. Drug substances/Product- intended for storage in Freezer
Study Storage condition Minimum time period
covered by data at
submission
Long term -20°C ± 5°C 12 months
4/25/2023 MMCP 80
Drug products - General case
Study Storage condition Minimum time period
covered by data at
submission
Long term 25°C ± 2°C / 60% ± 5% r.h. or
30°C ± 2°C / 65% ± 5% r.h.
12 months
Intermediate 30°C ± 2°C / 65% ± 5% r.h. 6 months
Accelerated 40°C ± 2°C / 75% ± 5% r.h. 6 months
81. Drug products - packaged in Semi-permeable containers
Study Storage condition Minimum time period
covered by data at
submission
Long term 25°C ± 2°C / 40% ± 5% r.h. or
30°C ± 2°C / 35% ± 5% r.h.
12 months
Intermediate 30°C ± 2°C / 65% ± 5% r.h. 6 months
Accelerated 30°C ± 2°C / 65% ± 5% r.h. 6 months
4/25/2023 MMCP 81
Drug products - intended for storage in a Refrigerator
Study Storage condition Minimum time period
covered by data at
submission
Long term 5°C ± 3°C 12 months
Accelerated 25°C ± 2°C / 60% ± 5% r.h. 6 months
82. . From the graph : time period to have 90% potency for each temperature namely
37°c, 45°c and 60°c were ascertained for Formulation F3 which are depicted in the
following table
Temperature under study Time required to have a 90%
potency (days) i.e.‘t’ 90%
37°C 262
45°C 192
60°C 95
4/25/2023 MMCP 82
CALCULATIONS FOR SHELF LIFE PREDICTION
‘t’ 90% values from the above table then convert into log ‘t’ 90% and their
coresponding temperature (t) into absolute temperature (‘T’). Then reciprocal of
absolute temperature 1/T was calculated at each temperature.
83. TABLE DEPICTING ‘t’90% ,1/TAND LOG ‘t’90%
VALUES FOR FORMULATION F3AT 37°C, 45°C
AND 60°C
Temperature
under study
‘t’ 90% (days) 1/T Log ‘t’ 90%
37°C 262 3.225*10-3 2.41
45°C 192 3.14*10-3 2.28
60°C 95 3.000*10-3 1.97
4/25/2023
MMCP 83
84. TABLE DEPICTING ‘t’90% ,1/TAND LOG ‘t’90%
VALUES FOR FORMULATION F3AT 37°C, 45°C
AND 60°C
At 30°C(RoomTemperature)
T = ‘t’ +273
= 30+273
T = 303 1/T=1/303=3.30*10-3
Depicts a plot between log t 90% and 1/T10-3 Formulation F3 at 37°C ,
45°C,60 °C.The straight line so obtained was extra plotted to 1/T
value at 30°C & the corresponding log ‘t’ at 30°C on y axis was noted
down. It was found to be 2.69.
Now log’ t’ 90% at 30°C = 2.69
‘t’ 90°C at 30°C = 490 days.
Therefore shelf life of formulation F3 in years = 490/365 = 1.342 years
or = 1.3 years.
4/25/2023
MMCP 84
88. REFERENCES
1. Ansel’s pharmaceutical Dosage forms & Drug delivery
systems, 8th edition by Loyd V. Allen, Nicholas G.popovich,
Howard C. Ansel, publised by B.I.Publication pvt. Ltd.,
page no:- 187-193,42 & 43,126-133.
2. Pharmaceutical preformulation by J.T.Cartensen published
by technomic publishing Co., page no:- 1-6, 211-212.
3. Textbook of physical pharmaceutics by C.V.S.
Subrahmanyam, published by Vallabh prakashan, page no:-
182-208, 222-226.
4/25/2023
MMCP 88
89. REFERENCES
4. The theory & practice of industrial pharmacy by
Leon Lachman, Herbert A. Lieberman, Joseph L.
kenig, 3rd edition, published by Varghese Publishing
house, page no:- 171-184.
5. Martin’s Physical pharmacy & Pharmaceutical
science, 5th edition by Patrick J. Sinco, Published by
Lippincott williams & wilkins, page no:- 547-550.
6. Pharmaceutical dosage forms : Tablet volume1,
edited by Herbert A. Lieberman & Leon Lachman,
published by Marcel dekker, page no:- 1-10.
4/25/2023
MMCP 89