Polymorphism is the ability of a solid material to exist in two or more crystalline forms. The document discusses the different types of polymorphism, factors that influence polymorphism, and methods to identify and produce polymorphs. It also outlines several applications of polymorphism in pharmaceuticals and organic chemistry. Specifically, selecting the right polymorph is important for drug stability, solubility, and bioavailability.
In this slide, you will learn about what is polymorphism, types, and properties of polymorphism, the application of polymorphism in pharmaceutical industries, polymorphism of several drugs. Hope you will like it.
The document discusses various techniques for enhancing the solubility of poorly soluble drugs. It begins by explaining the importance of drug solubility for bioavailability and outlines several techniques, including physical modifications like reducing particle size and modifying crystal forms, chemical modifications like changing pH, and forming complexes with agents. A key technique is using surfactants to create microemulsions that can solubilize drugs and enhance permeability across biological membranes. Overall, the techniques aim to increase surface area, modify crystal energy states, or alter a drug's chemistry to improve its solubility.
Polymorphism refers to a solid material existing in two or more crystalline forms with different arrangements in the crystal lattice. Over 50% of active pharmaceutical ingredients have more than one polymorphic form, which can exhibit different properties like solubility, dissolution rate, and stability. Methods to identify polymorphs include x-ray diffraction, differential scanning calorimetry, and thermal microscopy. The choice of polymorph is important for drug formulations, as the metastable form may have better bioavailability but convert to the stable form, impacting suspension stability or drug absorption. Case studies show certain polymorphs can be medically inactive or cause production issues if they convert dominant forms.
This document discusses drug dissolution, including definitions, theories, mechanisms, factors affecting dissolution, intrinsic dissolution rate, and in-vitro dissolution testing models. It defines dissolution as the process where a solid substance solubilizes in a solvent. The key theories of drug dissolution discussed are the diffusion layer model, Danckwert's model, and the interfacial barrier model. Factors that can impact dissolution include properties of the drug substance, dosage form excipients, test conditions, and more. Intrinsic dissolution rate is defined as the dissolution of pure substances under standardized conditions. Various in-vitro dissolution testing models are also summarized, including non-sink and sink methods.
Techniques for enhancement of dissolution rateSagar Savale
The document discusses various techniques to enhance the dissolution rate of drugs, which is important for predicting bioavailability. It describes the process of dissolution and factors that influence the rate based on the Noyes-Whitney equation. Several methods are covered, including increasing surface area through particle size reduction, using surfactants, solid dispersions, polymorphism, molecular encapsulation, salt formation, and nanosuspensions. Enhancing dissolution rate can improve drug efficacy by increasing bioavailability.
In this slide, you will learn about what is polymorphism, types, and properties of polymorphism, the application of polymorphism in pharmaceutical industries, polymorphism of several drugs. Hope you will like it.
The document discusses various techniques for enhancing the solubility of poorly soluble drugs. It begins by explaining the importance of drug solubility for bioavailability and outlines several techniques, including physical modifications like reducing particle size and modifying crystal forms, chemical modifications like changing pH, and forming complexes with agents. A key technique is using surfactants to create microemulsions that can solubilize drugs and enhance permeability across biological membranes. Overall, the techniques aim to increase surface area, modify crystal energy states, or alter a drug's chemistry to improve its solubility.
Polymorphism refers to a solid material existing in two or more crystalline forms with different arrangements in the crystal lattice. Over 50% of active pharmaceutical ingredients have more than one polymorphic form, which can exhibit different properties like solubility, dissolution rate, and stability. Methods to identify polymorphs include x-ray diffraction, differential scanning calorimetry, and thermal microscopy. The choice of polymorph is important for drug formulations, as the metastable form may have better bioavailability but convert to the stable form, impacting suspension stability or drug absorption. Case studies show certain polymorphs can be medically inactive or cause production issues if they convert dominant forms.
This document discusses drug dissolution, including definitions, theories, mechanisms, factors affecting dissolution, intrinsic dissolution rate, and in-vitro dissolution testing models. It defines dissolution as the process where a solid substance solubilizes in a solvent. The key theories of drug dissolution discussed are the diffusion layer model, Danckwert's model, and the interfacial barrier model. Factors that can impact dissolution include properties of the drug substance, dosage form excipients, test conditions, and more. Intrinsic dissolution rate is defined as the dissolution of pure substances under standardized conditions. Various in-vitro dissolution testing models are also summarized, including non-sink and sink methods.
Techniques for enhancement of dissolution rateSagar Savale
The document discusses various techniques to enhance the dissolution rate of drugs, which is important for predicting bioavailability. It describes the process of dissolution and factors that influence the rate based on the Noyes-Whitney equation. Several methods are covered, including increasing surface area through particle size reduction, using surfactants, solid dispersions, polymorphism, molecular encapsulation, salt formation, and nanosuspensions. Enhancing dissolution rate can improve drug efficacy by increasing bioavailability.
Accelerated stability testing exposes pharmaceutical products to elevated temperatures and humidity to rapidly determine their shelf life. Samples are stored at conditions like 40°C/75%RH and tested over time. The Arrhenius equation relates reaction rate constants at different temperatures, allowing prediction of shelf life at normal storage conditions from accelerated data. Limitations include reactions not dependent on temperature alone and products losing integrity at high stresses.
Polymorphism is very important in those areas of chemical research where full
characterization of a material has a pivotal role in determining its ultimate use, e.g., in
pharmaceutical, pigment, agrochemical, explosive, and fine chemical industries.
Polymorphism has been recognized as an important element of drug development
Polymorphic forms of a drug substance can have different chemical and physical
properties, including melting point, chemical reactivity, apparent solubility, apparent
solubility, dissolution rate, optical, electrical, and mechanical properties, vapor pressure,
stability, and density.
These properties can have a direct effect on the ability to process and/or manufacture the
drug substance and the drug product, as well as on drug product stability, dissolution, and
bioavailability.
Polymorphism is very common among pharmaceutical substances and thermodynamic
stability of a polymorph can impact pharmaceutical properties such as bioavailability,
processability and manufacturability.
Polymorphic forms possess higher potential energy with respect to the
thermodynamically stable or lowest entry forms.
Different polymorphic phase’s exhibit unique physicochemical properties include
solubility, dissolution rates which can influence bioavailability.
The ability to isolate, differentiate, and characterize individual polymorphs is a major
challenge to the pharmaceutical industry.
PHARMACEUTICAL APPLICATIONS OF POLYMORPHISM
- Improved physical stability
- Ease of handling
- Improved bioavailability
- Better chemical stability
- Sustained release
The document discusses various techniques to improve the solubility of poorly soluble drugs, including salt formation, co-solvency, and particle size reduction. It focuses on using salt formation between flurbiprofen and tris(hydroxymethyl)aminomethane to increase solubility. Analytical techniques like DSC, TGA, HPLC, and UV were used to characterize the flurbiprofen-tris salt and showed improved solubility over flurbiprofen alone. The conclusion states that increasing water solubility of insoluble drugs is important for developing effective dosage forms and delivering drugs to the absorption site.
This document discusses approaches to controlled release oral drug delivery systems using hydrodynamically balanced systems. It describes various gastrointestinal anatomy and physiology factors that influence gastric retention time such as size, density, and food intake. Several mechanistic approaches to achieve prolonged gastric retention are outlined, including high-density systems, bioadhesive systems, swelling and expanding systems, magnetic systems, superporous hydrogels, and floating systems. Floating drug delivery systems that form rafts or generate gas are described as important approaches to obtain sufficient drug bioavailability through gastric retention.
Dispersed systems consist of particulate matter dispersed in a continuous medium and are classified based on particle size as molecular dispersions, colloidal dispersions, or coarse dispersions. Colloidal dispersions have particle sizes between 1-1000 nm that are not visible under an ordinary microscope but can be seen under an electron microscope. Colloidal dispersions exhibit Brownian motion, diffusion, sedimentation, osmotic pressure, viscosity, and optical properties. The document then provides details on these various properties of colloidal dispersions.
This document provides an overview of a seminar presentation on drug stability given by Ms. Swati S. Bharati to Mumbai University. The presentation covers topics such as the importance of stability testing, degradation pathways including physical, chemical and microbial degradation, kinetic stability, and solution and solid state stability. It defines stability and the purpose of stability studies. Examples are provided to illustrate different types of degradation pathways and how they can be prevented.
This document discusses stability testing of drugs and pharmaceuticals. It covers factors that influence media effects and pH effects on stability. The document outlines the purpose of stability testing, which is to provide evidence on how drug quality varies over time under different environmental conditions. This ensures the quality of pharmaceuticals during distribution and storage. The document discusses guidelines for stability testing and defines terms like shelf life, retest date, accelerated testing and stress testing. It also covers the different climatic zones and conditions used for long-term stability testing.
This document provides an overview of solubility and dissolution. It defines key terms like solubility, dissolution, and saturation solubility. It discusses factors that affect solubility like temperature, particle size, and polarity. It also describes different techniques to improve solubility including use of co-solvents, surfactants, and complexation. Surfactants can improve solubility through micelle formation. The document is intended as an introduction to solubility and techniques to enhance solubility of poorly soluble drugs.
This document discusses chemical kinetics and drug stability. It begins by introducing chemical kinetics and its application to studying physical and chemical reactions in drugs and dosage forms. It then discusses the rates of different reaction orders (zero, first, second) and how to determine reaction order. Factors that can affect reaction rates are also covered. The document outlines methods for stability testing of drugs and formulations to ensure patient safety, legal compliance and product quality. It discusses causes of drug instability and approaches to prevent or delay degradation, including accelerated stability testing. Stability considerations for semi-solid and solid dosage forms are also addressed. Finally, international regulatory guidelines for stability studies from ICH and WHO are mentioned.
Preformulation studies characterize the physical and chemical properties of drug molecules to develop safe, effective, and stable dosage forms. The goals are to develop formulations that are stable, safe, and effective. Major areas of study include physical characterization of properties like crystallinity and polymorphism, hygroscopicity, particle size, and powder flow. Solubility is analyzed through measurements of ionization, partition coefficient, aqueous solubility, and pH-solubility profiles. Stability is analyzed through studies of photolytic stability, stability to oxidation, and drug-excipient compatibility.
This document discusses various techniques to improve the solubility of poorly soluble drugs, which is important for developing effective dosage forms and achieving desired drug concentrations. It defines solubility and discusses the importance of solubility in drug development. Some key techniques covered are co-solvency, use of surfactants, solid dispersions, complexation, changing temperature, hydrotropy, polymorphism, amorphous forms, solvates, salt formation, and micronization/nanonization. The goal is to select the optimal method for a given drug to enhance dissolution and absorption.
Preformulation part 1- Preformulation- Crystal, Amorphous, Polymorphism, Pseu...vijaysrampur
The document provides an introduction to preformulation, which involves studying the physical and chemical properties of a drug substance prior to formulation development. The goals of preformulation are to generate information to develop stable, bioavailable dosage forms and establish parameters that may affect drug performance. Key physical properties studied include organoleptic characteristics, bulk properties like solubility and polymorphism, and chemical properties like hydrolysis and oxidation. Understanding these characteristics is essential for designing optimal drug delivery systems. Preformulation is the first step in rational development of a dosage form.
This document discusses hard and soft gelatin capsules. Gelatin capsules enclose drug substances within soluble shells, usually made from gelatin derived from animal bones and hides. Hard gelatin capsules are prepared through dipping, spinning, drying, stripping and trimming processes. Soft gelatin capsules are manufactured using one of four methods: plate, rotary die, reciprocating die or Accogel machine. The document describes the soft gelatin capsule production process and lists common evaluation tests for capsules including weight variation, content uniformity, dissolution and disintegration.
1. The document discusses different types of deformation that solids undergo when external forces are applied, including elastic deformation, plastic deformation, and breaking.
2. Elastic deformation is reversible and follows Hooke's Law, relating stress to strain linearly. Plastic deformation is irreversible and leads to a permanent change in shape.
3. The document also defines moduli that quantify a material's resistance to different types of deformation, including Young's modulus, shear modulus, and bulk modulus. These properties depend on the material and can be used to characterize its stiffness.
The document discusses the HLB system for classifying emulsifying agents based on their hydrophilic-lipophilic balance. Emulsifying agents with HLB values between 3-6 produce water-in-oil emulsions, while those between 8-18 produce oil-in-water emulsions. It also describes common methods for preparing emulsions on a small scale, including the continental, English, and bottle methods. Factors that affect emulsion stability are creaming, coalescence, microbial deterioration, and physical or chemical changes over time. Proper use of emulsifiers, thickeners, preservatives, and storage conditions can help increase stability.
Drug-excipient compatibility studies are important to identify compatible excipients for drug formulations. Compatibility can be tested using various analytical techniques including thermal methods like DSC and DTA, accelerated stability studies, spectroscopy like FTIR, and chromatography like TLC. Incompatibilities are identified by changes in thermal behavior, degradation of the drug, or appearance of new peaks in analytical tests. Common techniques involve storing drug-excipient mixtures under accelerated conditions and monitoring the samples for physical or chemical changes over time. The results of compatibility studies provide critical information for formulation development and regulatory filings.
This document discusses an introduction to rheology and its importance in pharmacy. It begins by outlining the topics to be covered, which include the importance of rheology in pharmacy applications, definitions and fundamentals, types of fluids, viscosity, measurements of viscosity, instrumentation, and viscoelasticity. The first section defines rheology and describes its importance in areas like manufacturing dosage forms, handling drugs for administration, topical applications, and more. The introduction provides definitions of key terms like shear stress and rate of shear. It also describes Newton's laws of viscous flow. The document goes on to classify fluids as Newtonian or non-Newtonian and describes different types of non-Newtonian fluids.
Solid dispersion techniques can increase the dissolution and bioavailability of poorly water soluble drugs. This is done by improving the drug's solubility in water and enhancing oral absorption. There are various types of solid dispersions categorized by their miscibility and how drug molecules are distributed. Common preparation methods include melting, solvent evaporation, and melting solvent techniques. Solid dispersions produce colloidal drug particles that have higher dissolution rates and absorption compared to conventional dosage forms. Characterization methods include thermal analysis, X-ray diffraction, spectroscopy, and dissolution testing. Solid dispersions can improve drug stability, taste masking, and release from semisolid dosage forms.
Importance of partition coefficient, solubility and dissociation on pre-formu...SHANE_LOBO145
This document discusses the importance of preformulation studies, specifically focusing on partition coefficient, dissociation constant, and solubility. It defines these key terms and explains their significance in determining drug absorption and developing drug formulations. The partition coefficient indicates a drug's lipophilicity and ability to cross cell membranes. The dissociation constant and Henderson-Hasselbalch equation are used to predict drug ionization and site of absorption in the gastrointestinal tract. Solubility is critical for bioavailability and influences formulation strategies to increase or decrease a drug's aqueous solubility. Understanding these physicochemical properties is essential for designing an optimal drug delivery system.
This document discusses polymorphism as part of a preformulation study seminar. It defines polymorphism as the ability of a substance to exist in two or more crystalline forms that have different molecular arrangements. The key points covered include:
- The need to study polymorphism to select the most stable and soluble form for formulations. Metastable forms often have better bioavailability.
- Various methods to identify and characterize polymorphs such as X-ray diffraction, thermal analysis techniques like DSC and TGA, and microscopy.
- Factors that can influence polymorphic transitions like temperature, humidity, solvents, grinding, and compression during tableting.
- The importance of understanding polymorphism for properties like
Accelerated stability testing exposes pharmaceutical products to elevated temperatures and humidity to rapidly determine their shelf life. Samples are stored at conditions like 40°C/75%RH and tested over time. The Arrhenius equation relates reaction rate constants at different temperatures, allowing prediction of shelf life at normal storage conditions from accelerated data. Limitations include reactions not dependent on temperature alone and products losing integrity at high stresses.
Polymorphism is very important in those areas of chemical research where full
characterization of a material has a pivotal role in determining its ultimate use, e.g., in
pharmaceutical, pigment, agrochemical, explosive, and fine chemical industries.
Polymorphism has been recognized as an important element of drug development
Polymorphic forms of a drug substance can have different chemical and physical
properties, including melting point, chemical reactivity, apparent solubility, apparent
solubility, dissolution rate, optical, electrical, and mechanical properties, vapor pressure,
stability, and density.
These properties can have a direct effect on the ability to process and/or manufacture the
drug substance and the drug product, as well as on drug product stability, dissolution, and
bioavailability.
Polymorphism is very common among pharmaceutical substances and thermodynamic
stability of a polymorph can impact pharmaceutical properties such as bioavailability,
processability and manufacturability.
Polymorphic forms possess higher potential energy with respect to the
thermodynamically stable or lowest entry forms.
Different polymorphic phase’s exhibit unique physicochemical properties include
solubility, dissolution rates which can influence bioavailability.
The ability to isolate, differentiate, and characterize individual polymorphs is a major
challenge to the pharmaceutical industry.
PHARMACEUTICAL APPLICATIONS OF POLYMORPHISM
- Improved physical stability
- Ease of handling
- Improved bioavailability
- Better chemical stability
- Sustained release
The document discusses various techniques to improve the solubility of poorly soluble drugs, including salt formation, co-solvency, and particle size reduction. It focuses on using salt formation between flurbiprofen and tris(hydroxymethyl)aminomethane to increase solubility. Analytical techniques like DSC, TGA, HPLC, and UV were used to characterize the flurbiprofen-tris salt and showed improved solubility over flurbiprofen alone. The conclusion states that increasing water solubility of insoluble drugs is important for developing effective dosage forms and delivering drugs to the absorption site.
This document discusses approaches to controlled release oral drug delivery systems using hydrodynamically balanced systems. It describes various gastrointestinal anatomy and physiology factors that influence gastric retention time such as size, density, and food intake. Several mechanistic approaches to achieve prolonged gastric retention are outlined, including high-density systems, bioadhesive systems, swelling and expanding systems, magnetic systems, superporous hydrogels, and floating systems. Floating drug delivery systems that form rafts or generate gas are described as important approaches to obtain sufficient drug bioavailability through gastric retention.
Dispersed systems consist of particulate matter dispersed in a continuous medium and are classified based on particle size as molecular dispersions, colloidal dispersions, or coarse dispersions. Colloidal dispersions have particle sizes between 1-1000 nm that are not visible under an ordinary microscope but can be seen under an electron microscope. Colloidal dispersions exhibit Brownian motion, diffusion, sedimentation, osmotic pressure, viscosity, and optical properties. The document then provides details on these various properties of colloidal dispersions.
This document provides an overview of a seminar presentation on drug stability given by Ms. Swati S. Bharati to Mumbai University. The presentation covers topics such as the importance of stability testing, degradation pathways including physical, chemical and microbial degradation, kinetic stability, and solution and solid state stability. It defines stability and the purpose of stability studies. Examples are provided to illustrate different types of degradation pathways and how they can be prevented.
This document discusses stability testing of drugs and pharmaceuticals. It covers factors that influence media effects and pH effects on stability. The document outlines the purpose of stability testing, which is to provide evidence on how drug quality varies over time under different environmental conditions. This ensures the quality of pharmaceuticals during distribution and storage. The document discusses guidelines for stability testing and defines terms like shelf life, retest date, accelerated testing and stress testing. It also covers the different climatic zones and conditions used for long-term stability testing.
This document provides an overview of solubility and dissolution. It defines key terms like solubility, dissolution, and saturation solubility. It discusses factors that affect solubility like temperature, particle size, and polarity. It also describes different techniques to improve solubility including use of co-solvents, surfactants, and complexation. Surfactants can improve solubility through micelle formation. The document is intended as an introduction to solubility and techniques to enhance solubility of poorly soluble drugs.
This document discusses chemical kinetics and drug stability. It begins by introducing chemical kinetics and its application to studying physical and chemical reactions in drugs and dosage forms. It then discusses the rates of different reaction orders (zero, first, second) and how to determine reaction order. Factors that can affect reaction rates are also covered. The document outlines methods for stability testing of drugs and formulations to ensure patient safety, legal compliance and product quality. It discusses causes of drug instability and approaches to prevent or delay degradation, including accelerated stability testing. Stability considerations for semi-solid and solid dosage forms are also addressed. Finally, international regulatory guidelines for stability studies from ICH and WHO are mentioned.
Preformulation studies characterize the physical and chemical properties of drug molecules to develop safe, effective, and stable dosage forms. The goals are to develop formulations that are stable, safe, and effective. Major areas of study include physical characterization of properties like crystallinity and polymorphism, hygroscopicity, particle size, and powder flow. Solubility is analyzed through measurements of ionization, partition coefficient, aqueous solubility, and pH-solubility profiles. Stability is analyzed through studies of photolytic stability, stability to oxidation, and drug-excipient compatibility.
This document discusses various techniques to improve the solubility of poorly soluble drugs, which is important for developing effective dosage forms and achieving desired drug concentrations. It defines solubility and discusses the importance of solubility in drug development. Some key techniques covered are co-solvency, use of surfactants, solid dispersions, complexation, changing temperature, hydrotropy, polymorphism, amorphous forms, solvates, salt formation, and micronization/nanonization. The goal is to select the optimal method for a given drug to enhance dissolution and absorption.
Preformulation part 1- Preformulation- Crystal, Amorphous, Polymorphism, Pseu...vijaysrampur
The document provides an introduction to preformulation, which involves studying the physical and chemical properties of a drug substance prior to formulation development. The goals of preformulation are to generate information to develop stable, bioavailable dosage forms and establish parameters that may affect drug performance. Key physical properties studied include organoleptic characteristics, bulk properties like solubility and polymorphism, and chemical properties like hydrolysis and oxidation. Understanding these characteristics is essential for designing optimal drug delivery systems. Preformulation is the first step in rational development of a dosage form.
This document discusses hard and soft gelatin capsules. Gelatin capsules enclose drug substances within soluble shells, usually made from gelatin derived from animal bones and hides. Hard gelatin capsules are prepared through dipping, spinning, drying, stripping and trimming processes. Soft gelatin capsules are manufactured using one of four methods: plate, rotary die, reciprocating die or Accogel machine. The document describes the soft gelatin capsule production process and lists common evaluation tests for capsules including weight variation, content uniformity, dissolution and disintegration.
1. The document discusses different types of deformation that solids undergo when external forces are applied, including elastic deformation, plastic deformation, and breaking.
2. Elastic deformation is reversible and follows Hooke's Law, relating stress to strain linearly. Plastic deformation is irreversible and leads to a permanent change in shape.
3. The document also defines moduli that quantify a material's resistance to different types of deformation, including Young's modulus, shear modulus, and bulk modulus. These properties depend on the material and can be used to characterize its stiffness.
The document discusses the HLB system for classifying emulsifying agents based on their hydrophilic-lipophilic balance. Emulsifying agents with HLB values between 3-6 produce water-in-oil emulsions, while those between 8-18 produce oil-in-water emulsions. It also describes common methods for preparing emulsions on a small scale, including the continental, English, and bottle methods. Factors that affect emulsion stability are creaming, coalescence, microbial deterioration, and physical or chemical changes over time. Proper use of emulsifiers, thickeners, preservatives, and storage conditions can help increase stability.
Drug-excipient compatibility studies are important to identify compatible excipients for drug formulations. Compatibility can be tested using various analytical techniques including thermal methods like DSC and DTA, accelerated stability studies, spectroscopy like FTIR, and chromatography like TLC. Incompatibilities are identified by changes in thermal behavior, degradation of the drug, or appearance of new peaks in analytical tests. Common techniques involve storing drug-excipient mixtures under accelerated conditions and monitoring the samples for physical or chemical changes over time. The results of compatibility studies provide critical information for formulation development and regulatory filings.
This document discusses an introduction to rheology and its importance in pharmacy. It begins by outlining the topics to be covered, which include the importance of rheology in pharmacy applications, definitions and fundamentals, types of fluids, viscosity, measurements of viscosity, instrumentation, and viscoelasticity. The first section defines rheology and describes its importance in areas like manufacturing dosage forms, handling drugs for administration, topical applications, and more. The introduction provides definitions of key terms like shear stress and rate of shear. It also describes Newton's laws of viscous flow. The document goes on to classify fluids as Newtonian or non-Newtonian and describes different types of non-Newtonian fluids.
Solid dispersion techniques can increase the dissolution and bioavailability of poorly water soluble drugs. This is done by improving the drug's solubility in water and enhancing oral absorption. There are various types of solid dispersions categorized by their miscibility and how drug molecules are distributed. Common preparation methods include melting, solvent evaporation, and melting solvent techniques. Solid dispersions produce colloidal drug particles that have higher dissolution rates and absorption compared to conventional dosage forms. Characterization methods include thermal analysis, X-ray diffraction, spectroscopy, and dissolution testing. Solid dispersions can improve drug stability, taste masking, and release from semisolid dosage forms.
Importance of partition coefficient, solubility and dissociation on pre-formu...SHANE_LOBO145
This document discusses the importance of preformulation studies, specifically focusing on partition coefficient, dissociation constant, and solubility. It defines these key terms and explains their significance in determining drug absorption and developing drug formulations. The partition coefficient indicates a drug's lipophilicity and ability to cross cell membranes. The dissociation constant and Henderson-Hasselbalch equation are used to predict drug ionization and site of absorption in the gastrointestinal tract. Solubility is critical for bioavailability and influences formulation strategies to increase or decrease a drug's aqueous solubility. Understanding these physicochemical properties is essential for designing an optimal drug delivery system.
This document discusses polymorphism as part of a preformulation study seminar. It defines polymorphism as the ability of a substance to exist in two or more crystalline forms that have different molecular arrangements. The key points covered include:
- The need to study polymorphism to select the most stable and soluble form for formulations. Metastable forms often have better bioavailability.
- Various methods to identify and characterize polymorphs such as X-ray diffraction, thermal analysis techniques like DSC and TGA, and microscopy.
- Factors that can influence polymorphic transitions like temperature, humidity, solvents, grinding, and compression during tableting.
- The importance of understanding polymorphism for properties like
This document discusses preformulation studies, which focus on the physical and chemical properties of a new drug compound and how those properties could impact drug performance and dosage form development. The goals of preformulation studies are to establish the physicochemical parameters, kinetics, stability, and compatibility of a new drug compound alone and when combined with excipients. Key physicochemical properties investigated include particle size, shape, crystallinity, solubility, hygroscopicity, and stability. Understanding these properties helps with rational dosage form design and evaluation of product efficacy and stability.
Preformulation involves determining the physicochemical properties of new drug substances to establish parameters that may impact drug performance and dosage form development. Some key goals of preformulation testing include establishing a drug's physical characteristics, solubility, stability, and compatibility with excipients. Understanding properties like solubility, hygroscopicity, and powder flow help determine how a drug should be processed, stored, and formulated to ensure quality. Preformulation is an important first step in rational dosage form design.
This document discusses pre-formulation studies, which involve characterizing physicochemical properties of drug substances to provide information useful for developing stable and bioavailable dosage forms. Key aspects covered include determining drug degradation pathways, solubility, hygroscopicity, polymorphism, and thermal properties. The goal of pre-formulation is to understand factors influencing drug performance, stability, bioavailability, and dosage form development.
This document discusses preformulation for new drug development. A change in formulation, dosage, route of administration, or dosage form of an existing drug causes it to be considered "new" and requires safety and efficacy evaluation. Preformulation aims to optimize a drug's physical and chemical properties for a stable, effective dosage form. It involves characterizing the drug molecule and developing the dosage form. Some goals of preformulation include establishing the drug's physicochemical parameters, kinetic profile, physical characteristics, and compatibility with excipients. Polymorphism, or the ability of a drug to exist in different crystal forms, is also evaluated as it can impact properties like solubility, dissolution rate, and bioavailability.
The document discusses the use of metastable polymorphs to enhance oral bioavailability. It begins by defining polymorphism as the ability of a compound to crystallize in more than one distinct crystal structure. Metastable polymorphs are excited crystalline states that have longer lifetimes than ordinary excited states but shorter than the ground state. Using metastable polymorphs can improve properties like solubility and bioavailability. Several techniques to produce metastable polymorphs are described, like seeding, additives, and solvent control. Case studies demonstrate how metastable forms of drugs like famotidine and terazosin hydrochloride were approved generically. Regulatory considerations for showing sameness to the reference listed drug are also covered.
This document provides an overview of amorphous solid dispersions. It discusses glass transition temperature and how polymers can inhibit drug crystallization as a carrier matrix. Preparation methods like hot melt extrusion and solvent evaporation are described. Characterization techniques involve thermal analysis, spectroscopy and diffraction to analyze phase composition and molecular arrangement. In vitro tests examine the "spring and parachute" effect where drug dissolution increases initially before precipitation occurs without proper inhibition. Amorphous solid dispersions provide a formulation strategy for improving solubility of poorly water soluble drug candidates.
This document discusses the need for dosage forms and pre-formulation studies. It notes that dosage forms are needed to safely and conveniently deliver accurate drug doses while protecting drugs from environmental factors. Pre-formulation studies characterize the physical and chemical properties of drug substances to aid in the development of stable and effective dosage forms. These studies determine properties like solubility, stability, and compatibility with excipients. Understanding these properties provides insights to ensure quality during processing and storage.
Solid state stability and shelf-life assignment, Stability protocols,reports ...Durga Bhavani
This document discusses guidelines for solid state stability and shelf-life assignment studies as outlined by ICH. It provides definitions of stability, the need for stability studies, and factors that influence drug degradation like temperature, moisture, light and interactions. The document outlines the types of studies, including real-time and accelerated stability studies. It discusses stability protocols, reports, and test conditions recommended by ICH to determine a drug's shelf life.
This document discusses preformulation studies, which characterize the physicochemical properties of new drug molecules to develop safe, effective, and stable dosage forms. It covers various areas of preformulation research like organoleptic properties, bulk characterization, crystallinity, polymorphism, hygroscopicity, micromeritic properties, solubility, pKa determination, and stability studies. Analytical techniques used for characterization include microscopy, DSC, IR, XRD, SEM, and TGA. The goals of preformulation are to establish the drug's properties, determine its kinetics and stability, ensure compatibility with excipients, and improve the drug product's manufacturing, storage and performance.
A drug injected intravascularly directly enters the systemic circulation and exerts its pharmacological effects.
Majority of drugs administered extravascularly, generally orally.
If intended to act systemically, such drugs can exert their pharmacological actions only when they come into blood circulation from their site of application. So, absorption is an important step.
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.
1. Preformulation studies characterize the physical and chemical properties of drug molecules to develop safe, effective, and stable dosage forms.
2. Key areas of preformulation include evaluating organoleptic properties, bulk characterization, solubility analysis, and stability analysis.
3. Important parameters studied are particle size, hygroscopicity, crystallinity, polymorphism, and powder flow properties which can impact drug dissolution, bioavailability, stability and manufacturability of dosage forms.
This document discusses excipients and their role in drug formulations. It notes that excipients are ingredients other than the active pharmaceutical ingredient that are used to formulate dosage forms. Excipients can act as protective agents, bulking agents, and can improve drug bioavailability. The document then lists common types of excipients and potential interactions between drugs and excipients, such as physical, chemical, biopharmaceutical, and excipient-excipient interactions. It describes several analytical techniques used to detect drug-excipient interactions, including DSC, accelerated stability studies, FT-IR, DRS, chromatography methods, and others.
Preformulation studies characterize the physical and chemical properties of new drug molecules to aid in developing safe, effective, and stable dosage forms. The objectives are to establish physico-chemical parameters, determine kinetics and stability, and establish compatibility with excipients. Major areas of investigation include organoleptic properties, bulk characterization like crystallinity and polymorphism, solubility analysis including pH effects, and stability analysis of solutions and solids. Understanding these properties provides insights for processing and storage to ensure drug quality.
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.
English Drug and Alcohol Commissioners June 2024.pptxMatSouthwell1
Presentation made by Mat Southwell to the Harm Reduction Working Group of the English Drug and Alcohol Commissioners. Discuss stimulants, OAMT, NSP coverage and community-led approach to DCRs. Focussing on active drug user perspectives and interests
At Apollo Hospital, Lucknow, U.P., we provide specialized care for children experiencing dehydration and other symptoms. We also offer NICU & PICU Ambulance Facility Services. Consult our expert today for the best pediatric emergency care.
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2. CONTENT
6. Methods to
identify
polymorphism
5.methods of
polymorphism
9. Conclusion
10. Reference
8.Pharmacetiucal
application
2. Need to study
polymorphism
1. Intro
4.types of
polymorphism
3.Properties of
polymorphism
8. Polymorphism of
organic chemistry
7. Applications
3. Introduction
The term polymorph has been derived from Greek word "poly" which means "many"
and "morph" implying "form". Hence, polymorphism refers to different structural forms
of a chemical substance.
It is defind as the ability of a solid material to exist in two or more crystalline forms with
different arrangements or conformations in the crystal lattice.
Polymorphism can potentially be found in any crystalline material including polymers,
minerals, and metals, and is related to allotropy, which refers to chemical elements. The
complete morphology of a material is described by polymorphism and other variables
such as crystal habit, amorphous fraction or crystallographic defects. Polymorphism is
relevant to the fields of pharmaceutics. agrochemicals, pigments, dyestuffs, foods and
explosives.
4. More than 50% of active pharmaceutical ingredients (APIs) are estimated to have more
than one polymorphic form. Polymorphism and pseudomorphism are very common
amongst drugs and are responsible for differences in many properties.
The first observation of polymorphism is attributed to Friedrich Wohler and
Justus Von Liebig, in 1832. He was examining a boiling solution of organic solid
benzamide. During cooling, initially the benzamide is crystallized in the form of silky
needles but on standing they were slowly transformed or replaced into another form like
rhombic crystals.
The different crystal types are the result of hydration or salvation, in pseudo
polymorphism. Glycine is example for organic polymorph and is able to form mono
clinic and hexagonal crystals
5. Silica is the example for polymorphism and it forms many polymorphs such as a quartz,
ß-quartz, tridymite, cristobalite, coesite, and stishovite. A classic example for polymorph
are the minerals calcite and agagonite, both forms of calcium carbonate.
Polymorphism is exhibited in diamonds and graphite. Both diamond and graphite are
polymorphs of the same element carbon. Both the elements entirely consist of carbon but
they have different crystalline structures and physical properties, since the structure
determines the properties of the compounds
6. Need to study polymorphism
Depending upon their relative stability, one of the several polymorphic form will be
physically more stable than others.
Stable polymorph represents the lowest energy state, has highest melting point and
least aqueous solubility.
Metastable form represent the higher energy state, have lower melting point and
high aqueous solubility.
Metastable form converted to the stable form due to their higher energy state.
Metastable form shows better bioavailability and therefore preferred in
formulations.
7. Only 10% of the pharmaceuticals are present in their metastable form.
The effect of polymorphism on bioavilability is the most important consequencefor
drug substaces if the bioavailability is mediated via dissolution.
The example is chloramphenicol palmitate. Other like novobiocin, griseofulvine,
carbanazepine, aspirin and ampiciline.
The polymorphism of the excipients may also play an important role in bioavailability.
latest example: HYDOISOINDOLIN
8. Stability characteristics
Stable form
Meta form
Solubility
ratio-
solubility of
metastable
form/
solubility of
stable form
Stable form
having least
aqueous
solubility.
Meta form
having high
aqueous
solubility.
Depending upon
relative stability there
are two form of
polymorphs::
9. Dissolution behavior of polymorphs
Order of dissolution
rate:
amorphous>metastab
le>stable.
As the thermodynamic
activity of polymorph is
lower there is lower
apparent solubility and
thus absorption is also
less.
Among which dissolution
rate is one of the most
important.
The abosrption rate and
bioavailability of drug administered
orally is controlled by many factor.
Behaviour
10. Polymorphs shows the same properties in the liquid or gaseous state but they behave differently in solid
state.
Vapour
pressure
Solubility and
dissolution
rate
Hygroscopicity
Stability
Cryastal habit
Optical and
electrical
property
Melting and
sublimation
temperature
Properties of
polymorphism
11. Types of polymorphism
02
Enantiotropic
polymorph
Eg:Sulfur
01
Monotropic
polymorph
Eg:Glyceryl
stearate
Monotrophs only one polymorph is
stable at all temperature below the
melting point, with all other
polymorph being unstable.
Enantitrophs: if one form
stable over certain pressure
and temperature range. while
the other polymorph is stable
over different pressure and
temperature range.
15. 1. Solvent evaporation method (Rota Evaporation) :
In this approach, the saturated solution of the drug is prepared in an appropriate solvent and the solvent
is removed by rotatory evaporation. Air drying at various temperatures, can also be employed to obtain
different potential polymorphs.
2. Slow cooling approach:
This technique is frequently employed for the polymorphic forms of less soluble drugs in the solvent
systems having boiling point range of 30 to 90°C. In brief, the solute is heated in the solvent just above
the boiling point of the latter to produce the saturated solution. This solution is transferred to a stoppered
tube and is connected to a Dewar flask containing water at a temperature just below the boiling point of
the solvent. The Dewar flask is left in these conditions for several days. This technique may further be
improved to obtain better crystal forms using different solvent mixtures of different polarities. Variation in
the solvent composition may inhibit or promote growth of particular crystal faces and hence, can yield
crystals of the desired morphology. This approach is also called the solution growth approach.
3. Solvent diffusion technique :
This method is employed when the amount of drug available is less, and the drug is sensitive to air
and/or solvent(s). In this option, the solution is placed in a sample tube; subsequently a less dense
solvent is carefully dripped down the sides of the tube using either a pipette or a syringe to form a
discreet layer.
16. 4. Vapor diffusion method :
This method is analogous to the previous one and is also applicable for the less quantities of the sample. In
this case, the concentrated drug solution (0.5 µL to approximately 20 µL) is placed as a drop hanging on
the underside of a microscope cover slip.
The cover slip with the hanging drop is sealed with silicon oil over a solution (approx. 1 mL; reservoir)
containing high concentration of precipitant. Due to higher precipitant concentration, the latter has lower
vapor pressure than the drug solution. This results in diffusion of the solvent from the drop towards the
reservoir and subsequent crystallization of the API within hours to weeks.
18. Used in the identification of polymorphs crystal exist in isotropic and anisotropic form.
Isotropic examine the velocity of light is same in all direction.
Anisotropic crystal have 2 or 3 different light velocity or refractive indices.
Video recording system and polarizing microscope fitted during according to heating and cooling stage
for investigating polymorph.
Hot stage microscopy
Fluid stage transformation as a function of temperature is observed.
Silicon oil stage microscopy is used for detection of pseudopolymorph
X-ray diffraction method
It provide the most complete information about solid state.
This method is based on the scattering of x-ray by crystal.
Optical crystallography
19. Thermo gravimetric analysis
Is a type of testing that is performed on samples to determine changes in weight in relation to
change in temperature.
Such analysis relies on a high degree of precision in measurements; weight and temperature
changes.
As many weight loss similar, the weight loss curve may require transformation before results may
be interpreted.
20. Applications
The knowledge of solid-state properties in an early stage of development helps to avoid
manufacturing problems, to fine tune the performance of drugs and provides space for
innovations.
E,g.- Famotidine which is an excellent histamine
H2 receptor antagonist is also found to exist in two different polymorphic forms, metastable
polymorph B and stable polymorph A.
For improvement of therapeutic activity of drug.
To prevent loss of raw material.
• For better bioavailability of drug.
21. Pharmaceutical application of polymorphs
Suspension :
In preparation of suspension use of a wrong polymorph of a drug, a phase
conversion from the metastable to stable polymorph may occur. This results in crystal growth
and caking of suspension.
Eg:
cortisone acetate was one of the most difficult polymorphic problems to solve. Macek
obtained the first patent on stable noncaking aqueous suspension of cortisone acetate and
methods of preparing the same. He describe the early attempts to obtain a stable aqueous
suspension, where cortisone acetate, in the form of crystals stable in the dry state, was
suspended in the aqueous medium and allowed to remain in the medium for a few hours. It was
observed that crystals growth of the cortisone acetate invariably occurred with subsequent
caking and sedimentation.
A physically stable aqueous suspension was obtained by ball-milling
cortisone acetate powder, in the aqueous vehicle where a polymorphic phase transition
occurred. In a later patent, Magerlein described two new polymorphs of cortisone acetate, Form
A ,which is not stable in the dry state, and Form B, which is stable in the dry state. Both crystal
forms when used in aqueous suspensions gave physically stable, noncaking aqueous
suspension.
22. Creams:
When creams are prepared with the active ingredient suspended in the cream base. use of the
wrong polymorph can result in a phase inversion to a more stable phase. As a consequence,
crystal growth can occur in the vehicle yielding gritty, cosmetically unacceptable creams or
products in which the active ingredient is unevenly distributed. During the preparation of a
topical cream it is necessary to select the correct polymorph of the active ingredient, which
when suspended is least susceptible to growth in the cream base.
Solution:
Flynn has reported some problem in the formulation of a parenteral solution of a drug. In this
instance, determination of the water solubility of the compound indicated the drug to be
adequately soluble for the concentration required in the formulation. Stability studies on the
formulation quickly turned up the presence of a precipitate. An investigation of the problem
showed the precipitate to consist of a less soluble polymorph of the compound. The problem
was solved by formulating the product a vehicle containing sufficient cosolvent to solubilize
the less soluble polymorphic form.
23. Polymorphism in organic chemistry
Active pharmaceutical ingredients (APIS), frequently
delivered to the patient in the solid-state as part of an approved dosage form, can exist in such
diverse solid forms as polymorphs, pseudopolymorphs, salts, co-crystals and amorphous solids.
Various solid forms often display different mechanical, thermal, physical and chemical properties that
can remarkably influence the bioavailability, hygroscopicity, stability and other performance
characteristics of the drug. Hence, a thorough understanding of the relationship between the
particular solid form of an active pharmaceutical ingredient (API) and its functional properties is
important in selecting the most suitable form of the API for development into a drug product.
In past decades, there have been significant efforts on the
discovery, selection and control of the solid forms of APIs and bulk drugs. This contribution discusses
the thermodynamics and kinetics of polymorphic systems, the characterization of polymorphs, and the
transformation between polymorphs.
24. Conclusion
In the present era of evolving understanding, it is accepted that not merely chemical purity/integrity of the
API is the sole dependable and formulation influential parameter. The physical arrangements of the
constituents in the crystal lattice have immense potential to influence the physicochemical properties of
the drugs and subsequently the therapeutic outcomes. Therefore, the study of polymorphic forms has
become as important as any other branch of pharmaceutical sciences, as the former helps to embark
upon the proper API/excipient form selection.
with the foregoing discussion, it is clear that probably every organic medicinal can exist in different
polymorphs and the choice of the proper polymorph will determine if a pharmaceutical preparation will be
chemically or physically stable, or if a powder will tablet or not tablet well, or if the blood level obtained
will be the therapeutic level to give the pharmacologic response desired. Thus, it is time that
pharmaceutical companies, as a part of their pre- formulation studies, identify and study the stability of
different polymorphs of each potential new drug, as they do the melting points or other physical
characteristics.
25. REFERENCES
Karpinski PH. Polymorphism of active pharmaceutical ingredients. ChemEng Technol. 2006; doi:
10.1002/ceat.200500397.
Chawla G, Bansal AK. Challenges in polymorphism of pharmaceuticals. CRIPS. 2004. . The theory
and practice of industrial pharmacy by - Leon Lechman, Joseph L Kanig.
Biopharmaceutics and pharmacokinetics by- DM Bhramankar, Sunil Jaiswal.
Physical pharmacy by- Alfred Martine. Sun C. Grant DJW. Influence of crystal structure on the
tableting properties of sulfamerazine polymorphs. Pharm Res. 2001; 18(3):274-80.
Eyjolfsson R. Enalapril maleate polymorphs: instability of form II in a blet formulation. Phamazie. 2002;
57(5):347–48.
Schmidt AC, Senfter N, Griesser UJ. Crystal polymorphism of local anaesthetic drugs. J Therm Anal
Calorim. 2003: 73:397-404.