This document discusses complexation and protein binding. It defines complexes as molecules where most bonds can be described by classical theories of valency, but one or more bonds are anomalous. Complexes result from donor-acceptor or Lewis acid-base reactions between constituents.
It describes different types of complexes including metal complexes where the metal ion is the central atom. It also discusses organic molecular complexes formed between two organic molecules via hydrogen bonds or van der Waals forces. Inclusion complexes involve one compound being trapped in the lattice structure of another.
Various methods for analyzing complexes are presented, including determining stoichiometric ratios and stability constants using methods like continuous variation, distribution, solubility, and pH titration. Applications of complex
This document provides information on complexation and protein binding. It defines complexation as the association between two or more molecules to form a non-bonded entity through interactions like coordination bonds, van der Waals forces, hydrogen bonds, etc. It classifies complexes into metal complexes, organic molecular complexes, and inclusion complexes. It also discusses ligand types, methods of analyzing complexes, and applications of complexation. The document then defines protein binding and discusses factors that affect binding like drug and protein properties, drug interactions, and patient factors. It explains kinetics of protein binding and methods to determine binding constants and sites like direct plots, Scatchard plots, and others.
1. Complexation refers to the association of two or more interacting molecules or ions through coordinate bonding. This can occur between metal ions and ligands to form metal complexes, or between two organic molecules to form organic complexes.
2. Complexation has various applications in formulation such as improving physical state, reducing volatility, and enhancing solid state stability. It can also influence drug action by modifying properties like absorption, bioavailability, toxicity, and antibacterial activity.
3. Protein binding refers specifically to the formation of complexes between drug molecules and blood proteins. This binding affects the amount of free or unbound drug available to produce pharmacological effects.
This document discusses various physicochemical properties of drug molecules that are important for product development, including refractive index, optical rotation, dielectric constant, dipole moment, and dissociation constant. It provides definitions and measurement techniques for each property, as well as their applications in areas like product formulation, storage conditions, identification of substances, and understanding acid-base equilibria. Measurement of these properties allows for characterization of drug molecules and optimization of drug products.
State of matter and properties of matter (Part-3) (Eutectic mixture)Ms. Pooja Bhandare
This document discusses eutectic mixtures, which are mixtures of two or more phases that have the lowest melting point. A eutectic mixture is formed at a specific composition where the phases simultaneously crystallize from a molten solution. The term comes from the Greek word meaning "easily melted". Eutectic mixtures can be formed between APIs, APIs and excipients, or excipients. Below the eutectic temperature, the mixture exists as a solid, while above it exists as a liquid. Eutectic mixtures have various applications in the pharmaceutical industry, such as improving drug solubility and bioavailability for different routes of administration like oral, transdermal, parental, and nasal delivery.
A coordination complex is formed via a Lewis acid-base reaction between a central metal ion and surrounding ligands. Common ligands donate lone electron pairs to form coordinate covalent bonds with the metal. Coordination complexes have altered physical and chemical properties compared to the individual components. Complexation can impact drug properties like solubility, stability, and pharmacokinetics, which are important considerations in drug delivery and activity.
This document discusses pH, buffers, and isotonic solutions. It provides information on pH scales, how pH is determined through electrometric and colorimetric methods, and applications of buffers. Buffer solutions are defined as those that resist changes in pH when small amounts of acid or base are added. The mechanisms and properties of buffer action are explained. The Henderson-Hasselbalch equation relating the pH of a buffer solution to the ratio of concentrations of its weak acid and salt is derived. Factors affecting buffer capacity are also outlined.
This document provides information on complexation and protein binding. It defines complexation as the association between two or more molecules to form a non-bonded entity through interactions like coordination bonds, van der Waals forces, hydrogen bonds, etc. It classifies complexes into metal complexes, organic molecular complexes, and inclusion complexes. It also discusses ligand types, methods of analyzing complexes, and applications of complexation. The document then defines protein binding and discusses factors that affect binding like drug and protein properties, drug interactions, and patient factors. It explains kinetics of protein binding and methods to determine binding constants and sites like direct plots, Scatchard plots, and others.
1. Complexation refers to the association of two or more interacting molecules or ions through coordinate bonding. This can occur between metal ions and ligands to form metal complexes, or between two organic molecules to form organic complexes.
2. Complexation has various applications in formulation such as improving physical state, reducing volatility, and enhancing solid state stability. It can also influence drug action by modifying properties like absorption, bioavailability, toxicity, and antibacterial activity.
3. Protein binding refers specifically to the formation of complexes between drug molecules and blood proteins. This binding affects the amount of free or unbound drug available to produce pharmacological effects.
This document discusses various physicochemical properties of drug molecules that are important for product development, including refractive index, optical rotation, dielectric constant, dipole moment, and dissociation constant. It provides definitions and measurement techniques for each property, as well as their applications in areas like product formulation, storage conditions, identification of substances, and understanding acid-base equilibria. Measurement of these properties allows for characterization of drug molecules and optimization of drug products.
State of matter and properties of matter (Part-3) (Eutectic mixture)Ms. Pooja Bhandare
This document discusses eutectic mixtures, which are mixtures of two or more phases that have the lowest melting point. A eutectic mixture is formed at a specific composition where the phases simultaneously crystallize from a molten solution. The term comes from the Greek word meaning "easily melted". Eutectic mixtures can be formed between APIs, APIs and excipients, or excipients. Below the eutectic temperature, the mixture exists as a solid, while above it exists as a liquid. Eutectic mixtures have various applications in the pharmaceutical industry, such as improving drug solubility and bioavailability for different routes of administration like oral, transdermal, parental, and nasal delivery.
A coordination complex is formed via a Lewis acid-base reaction between a central metal ion and surrounding ligands. Common ligands donate lone electron pairs to form coordinate covalent bonds with the metal. Coordination complexes have altered physical and chemical properties compared to the individual components. Complexation can impact drug properties like solubility, stability, and pharmacokinetics, which are important considerations in drug delivery and activity.
This document discusses pH, buffers, and isotonic solutions. It provides information on pH scales, how pH is determined through electrometric and colorimetric methods, and applications of buffers. Buffer solutions are defined as those that resist changes in pH when small amounts of acid or base are added. The mechanisms and properties of buffer action are explained. The Henderson-Hasselbalch equation relating the pH of a buffer solution to the ratio of concentrations of its weak acid and salt is derived. Factors affecting buffer capacity are also outlined.
Complexation and Protein Binding [Part-1](Introduction and Classification an...Ms. Pooja Bhandare
Complexation: Classification of complexation:
Metal ion or co-ordination complexes :
Inorganic type Organic molecular complexes :
Quinhydrone type
Picric acid type
Caffeine and other drug complexes
Polymer type
Inclusion or occlusion compound
Channel lattice type
Layer type
Monomolecular type
Macromolecular type
Chelates
Olefin type
Aromatic type
Pi (п) complexes
Sigma (б) complexes
Sandwich complexes
The document discusses complexation, which is the combination of individual groups or molecules to form larger molecules or ions. Complexes are formed through coordination bonds between a central metal atom or ion and surrounding ligands. Ligands can be monodentate, bidentate, or polydentate. Complexation has applications in drug delivery through properties like enhanced solubility and stability. Metal ion complexes and organic molecular complexes are discussed as examples. Protein binding of drugs is another type of complexation that affects drug absorption, distribution, metabolism, and excretion by binding drugs and rendering them pharmacologically inactive. Factors influencing protein binding include drug properties, protein properties, and patient factors.
State of matter and properties of matter (Part-2) (Latent Heat, Vapour pressu...Ms. Pooja Bhandare
Latent Heat, Vapour pressure, Factor affecting vapour pressure, Surface area, Types of molecule, Temperature and Intermolecular forces, Sublimation Critical point
Physical Pharmaceutics-IUnit-IIISurface and Interfacial tension (Part-1)(Li...Ms. Pooja Bhandare
This document discusses liquid interfaces and surface and interfacial tension. It defines a liquid interface as the boundary between phases in contact, with surface referring specifically to the boundary between a liquid and gas. Surface tension is the force per unit length acting at right angles to the liquid surface and arises from cohesive intermolecular forces being imbalanced at the surface. Molecules in the bulk liquid experience equal attractive forces from all sides, while surface molecules only experience inward attraction. This imbalance causes the surface to contract and results in surface tension. Interfacial tension similarly describes the imbalance of forces at the boundary between immiscible liquids. Some examples of liquid surface tensions are provided.
1. The document discusses different types of complexes that can form between molecules, including metal ion complexes, organic molecular complexes, and inclusion complexes.
2. Metal ion complexes involve donation of electron pairs from ligands to a central metal ion. Important types include inorganic complexes containing ligands like ammonia, and chelate complexes where a ligand donates multiple electron pairs.
3. Organic molecular complexes are weaker and involve polarization of molecules and charge transfer rather than covalent bonding. Examples discussed include complexes of drugs containing N-C=S moieties that can complex with iodine.
Sanjo College of Pharmaceutical Studies, Physical Pharmaceutics I , 3rd semester B.Pharm, Complexation & protein binding, Classification in detail, determination methods, application of complexes in pharmacy.
Physical pharmacy i third semester (unit-i) solubility of drugMs. Pooja Bhandare
Physical pharmaceutics is the study of physicochemical properties of drug molecules in designing dosage forms. This document discusses the definitions and concepts related to solubility of drugs. It defines key terms like solute, solvent, saturated solution, and explains how solubility is expressed quantitatively and qualitatively. The mechanisms of solute-solvent interactions are discussed based on the nature of solvents being polar, non-polar or semi-polar. Specific examples are provided to illustrate solubility principles for different classes of solvents.
Complexation and Protein Binding [Part-2](Method of analysis, Complexation a...Ms. Pooja Bhandare
This document discusses various methods for analyzing complexes, including continuous variation (Job's) method, distribution method, solubility method, pH titration method, and spectroscopy. The continuous variation method analyzes changes in physical properties like dielectric constant when complexes form to determine stoichiometric ratios. The distribution method examines how the distribution of a solute between immiscible liquids changes with complexation to estimate stability constants. The solubility method observes whether solubility increases or decreases with the addition of a complexing agent. pH titration is reliable for complexes that affect pH upon formation. Spectroscopy techniques like UV and NMR are also used to determine rate constants and equilibrium constants.
Solubility of liquids in liquids, The term miscibility refers to the mutual solubility of the component of liquid - liquid system, Raoult’s Law, Raoult’s law may be mathematically expressed as: Ideal solution, Real solution
There are 6 main methods to analyze β-cyclodextrin complexes: 1) continuous variation method, 2) spectroscopy methods, 3) distribution methods, 4) pH titration methods, 5) solubility methods, and 6) general methods such as NMR spectroscopy and infrared spectroscopy. The document then provides details on the continuous variation, spectroscopy, pH titration, solubility, and distribution methods. It explains how each method can be used to determine stability constants and analyze complex formation between β-cyclodextrin and other molecules.
This document discusses complexation and protein binding. It defines complexes as molecules where some bonds cannot be described by classical valence theory. Complexation is the association of two molecules to form a non-covalently bonded entity with defined stoichiometry. Ligands interact with central metal ions or atoms in metal complexes. Protein binding is the formation of drug-protein complexes, which can impact drug absorption, distribution, metabolism, and action. Factors like drug and protein properties, concentrations, and interactions can influence protein binding. Common blood proteins that bind drugs include human serum albumin, glycoproteins, and lipoproteins.
State of matter and properties of matter (Part-6)(Relative humidity, Liquid ...Ms. Pooja Bhandare
RELATIVE HUMIDITY, Humidity, Wet and Dry Hygrometer, LIQUID COMPLEX, LIQUID CRYSTALS, Types of liquid crystals, GLASSY STATES, Characteristics glassy state, Types of glassy state, What is the Glass Transition Temperature?
This document discusses solubilization and surfactants. It defines solubilization as preparing an isotropic solution of an insoluble substance using a component or suitable method. Solubility is affected by the nature of solute and solvent, temperature, pressure, and particle size. Surfactants lower surface tension and act as detergents, wetting agents, etc. When added to water, surfactants self-assemble into micelles with hydrophilic heads facing out and hydrophobic tails inside in spherical, rod, or lamellar shapes above the critical micelle concentration. Micelle formation is driven by thermodynamics to increase entropy.
Quantitative approach to the to the factor influcing solubility of drug; (Sol...Ms. Pooja Bhandare
Quantitative approach to the to the factor influcing solubility of drugs, Temperature,Nature of solvent, The boiling point of the liquids and the melting point of solids,Crystal properties:
Particle size (surface area ) of drug particles: The influence of substituent’s in molecular structures, Molecular size:
. pH :
The document discusses coarse dispersions and suspensions. It defines a suspension as an insoluble solid dispersed in a liquid medium where the particles are larger than 0.1 μm. Common types of suspensions include orally administered, ophthalmic, and injectable suspensions. Desirable qualities include minimal settling, uniform distribution, and appropriate viscosity. The document outlines factors that influence particle interactions like surface energy and interfacial tension. It also discusses strategies to achieve stability including controlled flocculation, use of surfactants, polymers, and structured vehicles.
Solubility of drugs: Solubility expressions, mechanisms of solute solvent interactions, ideal solubility parameters, solvation & association, quantitative approach to the factors
influencing solubility of drugs, diffusion principles in biological systems. Solubility
of gas in liquids, solubility of liquids in liquids, (Binary solutions, ideal solutions)
Raoult’s law, real solutions. Partially miscible liquids, Critical solution temperature . Distribution law, its limitations and applications
This document discusses solubility of drugs and factors that influence drug solubility. It begins by listing topics that will be covered, including solubility expressions, mechanisms of solute-solvent interactions, ideal solubility parameters, solvation and association, quantitative approaches to factors influencing drug solubility, and principles of diffusion in biological systems. It then lists learning objectives which are to define solubility terms, understand solubility of gases, solids and liquids in liquids, and concepts such as Raoult's law, real solutions, phase diagrams and critical solution temperature. The document then discusses these topics in more detail over several pages.
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.
1. Complex compounds are molecules where some bonds cannot be described by classical theories of valency and involve anomalous bonds.
2. Complexes form through interactions like coordination bonds, hydrogen bonds, and van der Waals forces between different chemical species.
3. Complexation can alter properties like solubility, conductivity, and chemical reactivity and is used in applications like increasing drug solubility, purification of water, drug analysis, and as anticoagulants.
1. Complex compounds are molecules where most bonds can be described classically but one or more bonds are anomalous. They form through interactions like hydrogen bonding, ion-dipole forces, and coordination bonds.
2. Metal complexes are formed when a central metal atom bonds to surrounding ligands. Inorganic complexes include chelates where multidentate ligands bond to the metal. Organic molecular complexes are stabilized by weaker interactions like hydrogen bonding.
3. Complexes have applications in improving solubility, stability, and bioavailability of drugs. They are also used in water purification, analysis, and as catalysts.
Complexation and Protein Binding [Part-1](Introduction and Classification an...Ms. Pooja Bhandare
Complexation: Classification of complexation:
Metal ion or co-ordination complexes :
Inorganic type Organic molecular complexes :
Quinhydrone type
Picric acid type
Caffeine and other drug complexes
Polymer type
Inclusion or occlusion compound
Channel lattice type
Layer type
Monomolecular type
Macromolecular type
Chelates
Olefin type
Aromatic type
Pi (п) complexes
Sigma (б) complexes
Sandwich complexes
The document discusses complexation, which is the combination of individual groups or molecules to form larger molecules or ions. Complexes are formed through coordination bonds between a central metal atom or ion and surrounding ligands. Ligands can be monodentate, bidentate, or polydentate. Complexation has applications in drug delivery through properties like enhanced solubility and stability. Metal ion complexes and organic molecular complexes are discussed as examples. Protein binding of drugs is another type of complexation that affects drug absorption, distribution, metabolism, and excretion by binding drugs and rendering them pharmacologically inactive. Factors influencing protein binding include drug properties, protein properties, and patient factors.
State of matter and properties of matter (Part-2) (Latent Heat, Vapour pressu...Ms. Pooja Bhandare
Latent Heat, Vapour pressure, Factor affecting vapour pressure, Surface area, Types of molecule, Temperature and Intermolecular forces, Sublimation Critical point
Physical Pharmaceutics-IUnit-IIISurface and Interfacial tension (Part-1)(Li...Ms. Pooja Bhandare
This document discusses liquid interfaces and surface and interfacial tension. It defines a liquid interface as the boundary between phases in contact, with surface referring specifically to the boundary between a liquid and gas. Surface tension is the force per unit length acting at right angles to the liquid surface and arises from cohesive intermolecular forces being imbalanced at the surface. Molecules in the bulk liquid experience equal attractive forces from all sides, while surface molecules only experience inward attraction. This imbalance causes the surface to contract and results in surface tension. Interfacial tension similarly describes the imbalance of forces at the boundary between immiscible liquids. Some examples of liquid surface tensions are provided.
1. The document discusses different types of complexes that can form between molecules, including metal ion complexes, organic molecular complexes, and inclusion complexes.
2. Metal ion complexes involve donation of electron pairs from ligands to a central metal ion. Important types include inorganic complexes containing ligands like ammonia, and chelate complexes where a ligand donates multiple electron pairs.
3. Organic molecular complexes are weaker and involve polarization of molecules and charge transfer rather than covalent bonding. Examples discussed include complexes of drugs containing N-C=S moieties that can complex with iodine.
Sanjo College of Pharmaceutical Studies, Physical Pharmaceutics I , 3rd semester B.Pharm, Complexation & protein binding, Classification in detail, determination methods, application of complexes in pharmacy.
Physical pharmacy i third semester (unit-i) solubility of drugMs. Pooja Bhandare
Physical pharmaceutics is the study of physicochemical properties of drug molecules in designing dosage forms. This document discusses the definitions and concepts related to solubility of drugs. It defines key terms like solute, solvent, saturated solution, and explains how solubility is expressed quantitatively and qualitatively. The mechanisms of solute-solvent interactions are discussed based on the nature of solvents being polar, non-polar or semi-polar. Specific examples are provided to illustrate solubility principles for different classes of solvents.
Complexation and Protein Binding [Part-2](Method of analysis, Complexation a...Ms. Pooja Bhandare
This document discusses various methods for analyzing complexes, including continuous variation (Job's) method, distribution method, solubility method, pH titration method, and spectroscopy. The continuous variation method analyzes changes in physical properties like dielectric constant when complexes form to determine stoichiometric ratios. The distribution method examines how the distribution of a solute between immiscible liquids changes with complexation to estimate stability constants. The solubility method observes whether solubility increases or decreases with the addition of a complexing agent. pH titration is reliable for complexes that affect pH upon formation. Spectroscopy techniques like UV and NMR are also used to determine rate constants and equilibrium constants.
Solubility of liquids in liquids, The term miscibility refers to the mutual solubility of the component of liquid - liquid system, Raoult’s Law, Raoult’s law may be mathematically expressed as: Ideal solution, Real solution
There are 6 main methods to analyze β-cyclodextrin complexes: 1) continuous variation method, 2) spectroscopy methods, 3) distribution methods, 4) pH titration methods, 5) solubility methods, and 6) general methods such as NMR spectroscopy and infrared spectroscopy. The document then provides details on the continuous variation, spectroscopy, pH titration, solubility, and distribution methods. It explains how each method can be used to determine stability constants and analyze complex formation between β-cyclodextrin and other molecules.
This document discusses complexation and protein binding. It defines complexes as molecules where some bonds cannot be described by classical valence theory. Complexation is the association of two molecules to form a non-covalently bonded entity with defined stoichiometry. Ligands interact with central metal ions or atoms in metal complexes. Protein binding is the formation of drug-protein complexes, which can impact drug absorption, distribution, metabolism, and action. Factors like drug and protein properties, concentrations, and interactions can influence protein binding. Common blood proteins that bind drugs include human serum albumin, glycoproteins, and lipoproteins.
State of matter and properties of matter (Part-6)(Relative humidity, Liquid ...Ms. Pooja Bhandare
RELATIVE HUMIDITY, Humidity, Wet and Dry Hygrometer, LIQUID COMPLEX, LIQUID CRYSTALS, Types of liquid crystals, GLASSY STATES, Characteristics glassy state, Types of glassy state, What is the Glass Transition Temperature?
This document discusses solubilization and surfactants. It defines solubilization as preparing an isotropic solution of an insoluble substance using a component or suitable method. Solubility is affected by the nature of solute and solvent, temperature, pressure, and particle size. Surfactants lower surface tension and act as detergents, wetting agents, etc. When added to water, surfactants self-assemble into micelles with hydrophilic heads facing out and hydrophobic tails inside in spherical, rod, or lamellar shapes above the critical micelle concentration. Micelle formation is driven by thermodynamics to increase entropy.
Quantitative approach to the to the factor influcing solubility of drug; (Sol...Ms. Pooja Bhandare
Quantitative approach to the to the factor influcing solubility of drugs, Temperature,Nature of solvent, The boiling point of the liquids and the melting point of solids,Crystal properties:
Particle size (surface area ) of drug particles: The influence of substituent’s in molecular structures, Molecular size:
. pH :
The document discusses coarse dispersions and suspensions. It defines a suspension as an insoluble solid dispersed in a liquid medium where the particles are larger than 0.1 μm. Common types of suspensions include orally administered, ophthalmic, and injectable suspensions. Desirable qualities include minimal settling, uniform distribution, and appropriate viscosity. The document outlines factors that influence particle interactions like surface energy and interfacial tension. It also discusses strategies to achieve stability including controlled flocculation, use of surfactants, polymers, and structured vehicles.
Solubility of drugs: Solubility expressions, mechanisms of solute solvent interactions, ideal solubility parameters, solvation & association, quantitative approach to the factors
influencing solubility of drugs, diffusion principles in biological systems. Solubility
of gas in liquids, solubility of liquids in liquids, (Binary solutions, ideal solutions)
Raoult’s law, real solutions. Partially miscible liquids, Critical solution temperature . Distribution law, its limitations and applications
This document discusses solubility of drugs and factors that influence drug solubility. It begins by listing topics that will be covered, including solubility expressions, mechanisms of solute-solvent interactions, ideal solubility parameters, solvation and association, quantitative approaches to factors influencing drug solubility, and principles of diffusion in biological systems. It then lists learning objectives which are to define solubility terms, understand solubility of gases, solids and liquids in liquids, and concepts such as Raoult's law, real solutions, phase diagrams and critical solution temperature. The document then discusses these topics in more detail over several pages.
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.
1. Complex compounds are molecules where some bonds cannot be described by classical theories of valency and involve anomalous bonds.
2. Complexes form through interactions like coordination bonds, hydrogen bonds, and van der Waals forces between different chemical species.
3. Complexation can alter properties like solubility, conductivity, and chemical reactivity and is used in applications like increasing drug solubility, purification of water, drug analysis, and as anticoagulants.
1. Complex compounds are molecules where most bonds can be described classically but one or more bonds are anomalous. They form through interactions like hydrogen bonding, ion-dipole forces, and coordination bonds.
2. Metal complexes are formed when a central metal atom bonds to surrounding ligands. Inorganic complexes include chelates where multidentate ligands bond to the metal. Organic molecular complexes are stabilized by weaker interactions like hydrogen bonding.
3. Complexes have applications in improving solubility, stability, and bioavailability of drugs. They are also used in water purification, analysis, and as catalysts.
1.1 Introduction
1.2 Classification of Complexation
1.3 Applications, Methods of Analysis
1.4 Protein Binding
1.5 Complexation and the drug actions
1.6 Crystalline Structures of Complexes and Thermodynamic Treatment of Stability Constants.
This document discusses different types of metal ion complexes and protein binding. It describes inorganic complexes containing ligands such as ammonia and cyanide. Chelates form more stable complexes due to multiple bonding sites for the metal. Organic molecular complexes involve weaker interactions like hydrogen bonding or charge transfer. Inclusion complexes trap one component within the lattice structure of the other. Common examples discussed include hexamine cobalt chloride, caffeine complexes, and drug polymer interactions.
This document provides answers to questions about organic chemistry concepts. It defines key terms like catenation, isomerism, alkyl groups, functional groups, alkanes, and alkyl radicals. It also lists major commercial sources of alkanes, describes isomers and functional groups for several compounds, and provides structural formulas for alkanes and alkynes. The document aims to clarify fundamental organic chemistry concepts and distinguish between related terms.
This document defines complexation and provides classifications and examples of different types of complexes. It begins by defining complexes as molecules where most bonding can be described by classical theories but one or more bonds are anomalous. Complexes are classified as metal ion complexes, organic molecular complexes, or inclusion/occlusion complexes. Metal ion complexes include inorganic, chelate, and metal-olefin types. Organic molecular complexes involve weaker interactions and include drug-caffeine, polymer, picric acid, and quinhydrone types. Inclusion complexes trap one molecule within another's structure, including channel, layer, and clathrate types. Examples like starch-iodine and hydroquinone clathrates are provided.
This document provides definitions and classifications of complex compounds. It defines complexes as molecules where most bonding structures can be described by classical theories but one or more bonds are anomalous. Complexes result from donor-acceptor reactions between Lewis acids and bases. They are divided into metal ion complexes, organic molecular complexes, and inclusion complexes. Metal complexes involve coordination between metal ions and ligands. Chelates form cyclic structures with multidentate ligands. Organic complexes involve weaker interactions like hydrogen bonding. Inclusion complexes entrap guest molecules in host structures like channels, layers, or cavities. Common examples of complexes and their properties are discussed.
Complexation and plasma proteing pptindingssuser7add2a
Vineet Joshi discusses the process of complexation in pharmaceuticals. Complexation involves a ligand donating an electron pair to a metal ion, forming a coordinate covalent bond. This process can improve the physical state, volatility, solid state stability, chemical stability, solubility, dissolution, partition coefficient, absorption, bioavailability, and reduce toxicity of drugs. Some examples given include beta-cyclodextrin complexes improving the properties of nitroglycerin, vitamin A, vitamin D, and phenobarbital. Complexation can also be used to develop novel drug delivery systems and assay drugs containing metal ions.
The document discusses complexation and protein binding. It begins with introducing the topic and providing context about the course. It then discusses different types of complexes like chelates, olefin complexes, aromatic complexes, and organic molecular complexes. It describes how these complexes are formed through interactions like coordinate covalent bonds. It also discusses inclusion compounds, clathrates, and cyclodextrins which form cage-like structures to trap guest molecules. Protein binding and methods to determine drug-protein binding are also mentioned. The document provides an overview of different types of complexes and their applications in pharmaceuticals.
This document discusses complexation and protein binding. It defines complexation as interactions between two or more compounds capable of independent existence via covalent or non-covalent bonds. Complexes are classified as metal ion complexes or organic molecular complexes. Metal ion complexes include inorganic complexes, chelates, and aromatic complexes. Organic molecular complexes involve donor-acceptor interactions or hydrogen bonds. Complexation can enhance drug solubility, bioavailability, and modify drug properties. It is used in diagnosis, as a therapeutic tool, and to treat poisoning by facilitating removal of toxic substances from the body.
The document is a syllabus for the GPAT-2019 exam covering topics in physical chemistry, physical pharmacy, and organic chemistry. Some key topics included are:
1. Physical chemistry topics like thermodynamics, electrochemistry, kinetics, and solutions.
2. Physical pharmacy topics like surface phenomena, rheology, dispersion systems, and solubility.
3. Organic chemistry topics like functional group chemistry, aromatic compounds, carbonyl reactions, heterocyclic chemistry, and stereochemistry.
The syllabus provides an overview of the concepts and reactions to be covered in each topic for the exam.
This document summarizes the synthesis of polymers containing terpyridine ligands for binding metal ions. It describes (1) creating resorcinol monomers containing terpyridine ligands using a Suzuki coupling, (2) removing methyl groups to allow polymerization, (3) polymerizing the monomers, (4) attaching metal ions like palladium and copper to the polymers, and (5) conducting Suzuki reactions to test the polymer-bound catalysts. Preliminary results suggest the desired product is formed using a single polymer sample for multiple reactions.
This document discusses the use of organic reagents in quantitative analysis techniques like gravimetric analysis, volumetric analysis, spectrophotometry, and chromatography. It focuses on gravimetric analysis, describing the key steps of preparing a solution, separating the desired constituent, weighing the isolated constituent, and calculating the amount in the sample. Precipitation is a common gravimetric technique that uses a precipitating agent to isolate an analyte from solution based on the formation and mass of the precipitate. Organic reagents can also be used as indicators, titrants, and masking/demasking agents in volumetric analysis. Complexometric titrations often use organic dyes as indicators to signal the completion of metal-EDTA complex
Learning objectives
Introduction
Complexing agents
Complexing Titration using EDTA
Need for Maintenance of pH
pH Indicators used in complexometric Titrations
Types of EDTA Titration
Factors Influencing EDTA reaction
Masking and demasking agents
Conclusion
Reference
complexometric titration , colorimetry and spectrophotometry ushaSanmugaraj
it consists of notes for complexometric titration principle, edta, procedure, applications. colorimetry and spectrophotometry principle, introduction, instrumentation and applications
Classification of dispersed systems & their general characteristics, size & shapes of colloidal particles, classification of colloids & comparative account of their general properties. Optical, kinetic & electrical properties. Effect of electrolytes, coacervation, peptization& protective action.
Properties of amino acids:
- Amino Acids have an Asymmetric Center
- D and L stereoisomerism of amino acids
- Acid-Base Properties of Amino Acids
- Titration of amino acids
- Absorption
- Solubility
- Chemical properties of amino acid
Coordination compounds are complex compounds where transition metals are bound to anions or neutral molecules. They follow postulates put forth by Werner in 1898. Coordination compounds have important applications in qualitative and quantitative analysis, extraction and purification of metals, biological systems, industry, and medicine. They are used as catalysts, in electroplating, photography, chelate therapy, and some are effective in inhibiting tumor growth.
Similar to Pharmaceutical Complexation and Protein Binding (20)
This document discusses various parameters used to characterize drug release from pharmaceutical formulations, including diffusion parameters described by Higuchi's equation, dissolution parameters like the effects of agitation and pH, and pharmacokinetic parameters like Cmax, Tmax, and AUC. It also covers models like the Heckel equation that can be applied to understand powder compaction and the Korsmeyer-Peppas model for characterizing drug release mechanisms.
This document discusses optimization techniques used in pharmaceutical development. It defines optimization as choosing the best alternative from available options to make something as perfect or effective as possible. It discusses various optimization parameters like problem type (constrained vs unconstrained), variables (independent vs dependent), and methods like response surface methodology, factorial designs, evolutionary operations, and search methods. Response surface methodology uses statistical experimental designs like central composite designs to determine the relationship between independent and dependent variables and find the optimum formulation.
The document discusses ethics in computing in pharmaceutical research and computer use in market analysis. It addresses key ethical issues like privacy, liability, ownership, and power related to use of computers. It also discusses relevant codes of conduct for computer use and how computers can be used in market analysis to facilitate collection and dissemination of market information. A survey was conducted of industry participants to assess potential acceptance of computer-aided marketing systems. The advisory committee concluded such a system should be developed to complement existing marketing practices.
Quality by Design (QbD) is a systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding based on sound science and quality risk management. Key aspects of QbD include establishing a Quality Target Product Profile (QTPP) that identifies critical quality attributes (CQAs), understanding critical material attributes (CMAs) and critical process parameters (CPPs), and implementing a control strategy for CQAs and CPPs. The ICH Q8 guideline introduced QbD, and it has been further developed through guidelines like ICH Q9 and Q10. Examples show how QbD has been applied scientifically in different pharmaceutical development and manufacturing processes.
This document discusses the application of computer-aided techniques in developing pharmaceutical emulsions and microemulsions. It provides several examples of how experimental design and artificial neural networks have been used to optimize emulsion formulations and processing parameters. Specifically, researchers have used factorial design, response surface methodology, and artificial neural networks to determine the ideal concentrations of formulation components, processing conditions, and emulsifier mixtures to produce emulsions with desirable properties like stability, viscosity, and particle size. These computer-aided approaches allow for simultaneous optimization of multiple formulation parameters and provide a way to shorten product development time compared to traditional trial-and-error methods.
This document discusses various solubilization techniques for improving the solubility of poorly soluble drugs, including physical and chemical modifications. Under physical modifications, it covers crystal modification techniques like polymorphism and salt formation. It also discusses particle size reduction methods like micronization, nanonization, and production of nanosuspensions. Other techniques covered are drug dispersion in carriers through solid solutions, eutectic mixtures and solid dispersions. It also discusses solubilization using surfactants, complexation, and chemical modifications. The techniques discussed aim to improve drug dissolution rates and oral absorption of class II drugs limited by solubility.
This document discusses factors that affect drug absorption in the gastrointestinal (GI) tract. It covers pharmaceutical factors like a drug's solubility, particle size, salt form, and polymorphism/amorphism, which can impact dissolution rate and absorption. It also discusses patient-related factors like age, GI pH, transit time, and disease status. Key pharmaceutical factors that influence drug absorption are solubility, dissolution rate, and factors that impact effective surface area like particle size.
This document provides an overview of parenterals (injectable drugs). It discusses:
- Definitions and routes of administration including subcutaneous, intramuscular, intravenous, and others
- Formulation components like vehicles, buffers, antioxidants, and preservatives
- Manufacturing facilities and processes including design of aseptic areas, environmental controls, and personnel requirements
- Quality control tests for parenterals including clarity, leakage, sterility, and pyrogen testing
This document discusses the three common states of matter - gases, liquids, and solids. It provides details on the properties and behaviors of each state. Gases have widely separated molecules and are compressible. Liquids have more tightly packed molecules and are relatively incompressible. Solids have molecules in close contact that do not move and are nearly incompressible. The document then focuses more on properties of solids, including crystalline and amorphous structures. It also discusses phase equilibria, liquid crystals, and properties of gases including gas laws and the ideal gas equation.
This document discusses rheology, which is the branch of physics dealing with the deformation and flow of liquids. It provides definitions and examples of different types of fluid flow, including Newtonian, plastic, pseudoplastic, and dilatant flow. Key aspects covered include viscosity, shear stress, yield value, and the effects of temperature, particle concentration, and other factors on rheological properties. Common instruments used to measure viscosity, such as capillary, falling sphere, cup and bob, and cone and plate viscometers are also described.
This document discusses interfacial phenomena and surface tension. It begins with definitions of interface, surface tension, and interfacial tension. Several methods for measuring surface tension are described, including the capillary rise method, Du-Nouy ring method, and stallagmometric method. The concepts of surface free energy, spreading coefficient, and surface active agents are also introduced.
1. The document discusses colloidal dispersions, which are systems where particles between 1 nm and 1000 nm are dispersed uniformly throughout a dispersion medium.
2. Colloidal systems are classified based on particle size into molecular dispersions, colloidal dispersions, and coarse dispersions. They are also classified based on particle-medium interactions into lyophilic, lyophobic, and association colloids.
3. The key properties of colloidal systems discussed are electrical properties (surface charge, zeta potential, electrophoresis), optical properties (Tyndall effect, turbidity), and kinetic properties (Brownian motion, diffusion, viscosity).
1. The document discusses regulatory requirements for drug approval, including non-clinical and clinical studies that must be conducted and submitted to regulatory agencies like the FDA.
2. It describes the various teams involved in drug development, including discovery, preclinical, clinical, manufacturing, and marketing teams. The responsibilities and roles of each team are provided.
3. The approval process is outlined, including requirements for an Investigational New Drug (IND) application to the FDA. The IND must provide data from animal and other preclinical studies. It allows clinical trials to proceed if approved by the FDA within 30 days.
Total quality management (TQM) is a management approach focused on customer satisfaction through continual improvement. It involves all employees and emphasizes strategic planning, fact-based decision making, and effective communication. TQM aims to hold all parties accountable for quality and can improve profitability, customer satisfaction, productivity, and employee morale. Quality by design (QbD) is a concept where quality is planned and designed into products and processes from the development stage to reduce issues and meet customer needs.
This document discusses emulsions and self-emulsifying drug delivery systems (SEDDS). It defines emulsions as mixtures of two immiscible liquids stabilized by an emulsifying agent. The main types of emulsions described are oil-in-water, water-in-oil, multiple emulsions, and microemulsions. SEDDS are defined as isotropic mixtures of oils, surfactants, and co-solvents/co-surfactants that spontaneously form emulsions when exposed to aqueous media and can improve drug solubility and bioavailability. Key factors in developing SEDDS like choice of oils, surfactants, and evaluation methods are also summarized.
The document discusses suspensions, which are two-phase systems composed of solid particles dispersed in a liquid. Suspensions can be classified based on particle size as molecular, colloidal, or coarse dispersions. They can also be classified as flocculated or deflocculated based on how the particles interact. Factors like particle size, viscosity, density, and interfacial properties affect suspension stability. Common methods for producing suspensions include precipitation, dispersion, and controlled flocculation. The stability of suspensions is evaluated through sedimentation volume, degree of flocculation, and zeta potential measurements. Equipment like colloid mills and ultrasonic devices can be used to formulate suspensions.
This document discusses various parameters used to characterize drug release from pharmaceutical formulations. It describes diffusion parameters defined by Higuchi's equation and plots. Dissolution parameters like the effects of agitation, pH, temperature, and medium properties are outlined. Pharmacokinetic parameters including Cmax, Tmax, and AUC are defined. The Heckel equation is presented as a method to analyze powder compaction. Similarity factors f1 and f2 are introduced to compare dissolution profiles. The Higuchi and Korsmeyer-Peppas models for drug release are presented.
The document discusses kinetics of stability and accelerated stability testing. It provides details on zero order, first order and second order reactions. It explains the determination of rate constants, half life and time for 90% degradation using kinetic equations. The document also discusses Arrhenius equation for predicting shelf life from accelerated stability studies conducted at elevated temperatures. It summarizes the guidelines for stability testing of active pharmaceutical ingredients and finished pharmaceutical products as per ICH.
The document discusses different analytical techniques used to analyze drug-excipient interactions, including thermogravimetric analysis (TGA), differential thermal analysis (DTA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and FT-IR spectroscopy. Each technique is described in one to two sentences. TGA measures mass changes as temperature changes and provides information on physical and chemical phenomena like decomposition. DTA and DSC measure the temperature and heat flow differences between a sample and reference to determine endothermic and exothermic reactions like melting. XRD analyzes diffraction patterns to characterize crystal structure and polymorphism. FT-IR identifies functional groups and structures by analyzing absorption peaks.
This document provides an overview of pharmaceutical packaging. It discusses the functions of packaging including protection, storage, identification and information provision. It describes common packaging materials like glass, plastic, metal and rubber and how they are used. Different dosage forms like solids, liquids, and parenterals are outlined along with their typical packaging. Recent trends in the industry toward devices like prefilled syringes and regulations from the FDA are also summarized.
it describes the bony anatomy including the femoral head , acetabulum, labrum . also discusses the capsule , ligaments . muscle that act on the hip joint and the range of motion are outlined. factors affecting hip joint stability and weight transmission through the joint are summarized.
Walmart Business+ and Spark Good for Nonprofits.pdfTechSoup
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This presentation includes basic of PCOS their pathology and treatment and also Ayurveda correlation of PCOS and Ayurvedic line of treatment mentioned in classics.
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How to Build a Module in Odoo 17 Using the Scaffold MethodCeline George
Odoo provides an option for creating a module by using a single line command. By using this command the user can make a whole structure of a module. It is very easy for a beginner to make a module. There is no need to make each file manually. This slide will show how to create a module using the scaffold method.
How to Add Chatter in the odoo 17 ERP ModuleCeline George
In Odoo, the chatter is like a chat tool that helps you work together on records. You can leave notes and track things, making it easier to talk with your team and partners. Inside chatter, all communication history, activity, and changes will be displayed.
LAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UPRAHUL
This Dissertation explores the particular circumstances of Mirzapur, a region located in the
core of India. Mirzapur, with its varied terrains and abundant biodiversity, offers an optimal
environment for investigating the changes in vegetation cover dynamics. Our study utilizes
advanced technologies such as GIS (Geographic Information Systems) and Remote sensing to
analyze the transformations that have taken place over the course of a decade.
The complex relationship between human activities and the environment has been the focus
of extensive research and worry. As the global community grapples with swift urbanization,
population expansion, and economic progress, the effects on natural ecosystems are becoming
more evident. A crucial element of this impact is the alteration of vegetation cover, which plays a
significant role in maintaining the ecological equilibrium of our planet.Land serves as the foundation for all human activities and provides the necessary materials for
these activities. As the most crucial natural resource, its utilization by humans results in different
'Land uses,' which are determined by both human activities and the physical characteristics of the
land.
The utilization of land is impacted by human needs and environmental factors. In countries
like India, rapid population growth and the emphasis on extensive resource exploitation can lead
to significant land degradation, adversely affecting the region's land cover.
Therefore, human intervention has significantly influenced land use patterns over many
centuries, evolving its structure over time and space. In the present era, these changes have
accelerated due to factors such as agriculture and urbanization. Information regarding land use and
cover is essential for various planning and management tasks related to the Earth's surface,
providing crucial environmental data for scientific, resource management, policy purposes, and
diverse human activities.
Accurate understanding of land use and cover is imperative for the development planning
of any area. Consequently, a wide range of professionals, including earth system scientists, land
and water managers, and urban planners, are interested in obtaining data on land use and cover
changes, conversion trends, and other related patterns. The spatial dimensions of land use and
cover support policymakers and scientists in making well-informed decisions, as alterations in
these patterns indicate shifts in economic and social conditions. Monitoring such changes with the
help of Advanced technologies like Remote Sensing and Geographic Information Systems is
crucial for coordinated efforts across different administrative levels. Advanced technologies like
Remote Sensing and Geographic Information Systems
9
Changes in vegetation cover refer to variations in the distribution, composition, and overall
structure of plant communities across different temporal and spatial scales. These changes can
occur natural.
How to Fix the Import Error in the Odoo 17Celine George
An import error occurs when a program fails to import a module or library, disrupting its execution. In languages like Python, this issue arises when the specified module cannot be found or accessed, hindering the program's functionality. Resolving import errors is crucial for maintaining smooth software operation and uninterrupted development processes.
RPMS TEMPLATE FOR SCHOOL YEAR 2023-2024 FOR TEACHER 1 TO TEACHER 3
Pharmaceutical Complexation and Protein Binding
1. Presented by
(Dr) Kahnu Charan Panigrahi
Asst. Professor, Research Scholar,
Roland Institute of Pharmaceutical Sciences,
(Affiliated to BPUT)
Web of Science Researcher ID: AAK-3095-2020
Complexation
And Protein Binding
2. Complex compounds are defined as those molecules in
which most of the bonding structures can be described by
classical theories of valency between atoms, but one/more
of these bonds are some what anomalous.
Complexes or coordination compounds, according to the
classic definition, result from a donor–acceptor mechanism
or Lewis acid–base reaction between two or more different
chemical constituents.
Intermolecular forces involved in the formation of
complexes are the van der Waals forces of dispersion,
dipolar, and induced dipolar types. Hydrogen bonding
provides a significant force in some molecular complexes,
and coordinate covalence is important in metal complexes
4. I) Metal complexes:
METAL
(substrate)
Central atom
BASE
(ligand)
Electron pair donor
COMPLEX
formed by
co-ordination
bond
In this complex metal ion constitute the central atom and
interact with a base.
5. A) INORGANIC COMPLEXES:
Werner postulates:
1. There are 2 types of valency primary (ionic), secondary
(coordinate).
2. Same type of anion/ radical/ molecule may be held by any one /
both type of valency.
3. Every central atom has fixed number of non-ionic valences (co-
ordination number)
4. The co-ordination atoms occupy the first sphere/coordination
sphere, other atoms occupy second/ ionization sphere.
5. Neutral molecules/ions may satisfy non-ionic valency.
6. The non-ionic valences are directed to specific positions in space.
Ex: [Co Cl (NH3)5] Cl2
Substrate Coordination sphere
Ionization sphere
6. Ex: [Co Cl (NH3)5] Cl2
1. Compound ionize to form [Co Cl (NH3)5]+2 and 2Cl- .
2. Central chlorine do not precipitate with silver nitrate.
3. Substrate and ligand are bonded with coordination bond.
4. Coordination number is maximum number of atoms and groups
that combine with central atom in coordination sphere.
5. Co-ordination number for cobalt is 6.
Participate in
complexation
B) CHELATES:
These are group of metal ion complexes in which a substrate/ ligand
provides 2/more donor groups to combine with a metal ion. (In case
of inorganic complex only one donor group present)
Ligands-didentate, tridentate, polydentate.
7. Hexadentate -
Ethylenediaminetetraacetic acid
(EDTA)- Has a total of six points
(4:0 and 2: N) for attachment of
metal ions.
Sequestering:
This is a process in which the property of
metal is suppressed without removing it
from the solution.
Sequestering Agent:
This is a ligand which forms a stable
water soluble metal chelate
Ex: chlorophyll, hemoglobin.
8. Chelates applications:
1. INCREASING SOLUBILITY:
Fruit juices and drugs (ascorbic acid) + Fe/Cu oxidative
degradation.
Add EDTA + Fe/Cu stable Chelate
2. PURIFICATION OF HARD WATER:
Hard water (Ca+2) + EDTA EDTA-Ca+2 (ppt)
3. DURG ANALYSIS:
Procainamide + cupric ions (1:1) at pH 4-4.5 Coloured complex
detect by Colourimetry.
4. ANTI-COAGULANT:
Blood (Ca+2) + EDTA/Citrates/Oxalates prevent thrombin
formation no clotting.
9. C,D: OLEFIN AND AROMATIC TYPE:
a. These involves Lewis acid-base reactions
b. These type of complexes can be used as catalysts in the
manufacturing of bulk drugs, intermediates and in drug
analysis.
10. II. ORGANIC MOLECULAR COMPLEXES:
1. Interaction between 2 organic molecules Complex
temperature change molecular compound.
2. These complexes have (H)bonds/ weak vander wall forces/
dipole-induced dipole interactions.
3. Energy of attraction is 3K.Cal/mole
4. Bond distance is 3A0
11. MECHANISM:
1. Donar-Acceptor type:-
Bonds between uncharged species is formed and stabilized by
dipole-dipole interactions.
EX: N-Dimethyl aniline + 2,4,6-Trinitro anisole.
2. Charge transfer
complexes:-
Complex is stabilized by resonance.
Ex: Benzene + Trinitro benzene.
12. A) DRUG & CAFFINE COMPLEX:
Acidic drugs (benzocaine, procaine) + Caffeine Complexes
Mechanism:
1. dipole-dipole forces/ hydrogen bonding between acid (H) atom
and caffeine carboxyl group.
2. Interaction of non-polar parts
Ex: Caffeine + Benzocaine.
13. DRUG & CAFFINE COMPLEX APPLICATIONS:
1. These complexes can improve / extend absorption and
bioavailability of drug.
2. These complexes can enhance/ inhibit solubility and dissolution
rate of drug.
3. Caffeine+ gentisic acid complexes mask bitter taste of caffeine.
B) POLYMER COMPLEXES:
Polymers with nucleophilic oxygen (PEG/CMC)
+Drugs(tannic acid/salicylic acid/phenols) Complexes.
Disadvantages:
1. Incompatibilities in suspension, emulsion, ointments.
2. Complexes + Container drug loss
3. Complexes + preservatives decrease preservative action.
14. C) PICRIC ACID COMPLEXES:
Picric acid (strong acid) + strong base Salt.
Picric acid (strong acid) + weak base Complexes.
Ex: BUTESIN PICRATE
Picric acid (antiseptic) + Butesin (anesthetic)
(Ratio- 2:1)
1% ointment used for burns and abrasions.
15. D) QUINHYDRONE COMPLEXES:
Alcoholic solutions of equimolar quantities of Hydroquinone and
Benzoquinone form Quinhydrone complexes (green crystals)
Mechanism:
1. Overlapping of π electrons of molecules
2. (H) bonding for stabilizing complex.
Applications:
Used as electrode in pH determination.
Hydroquinone
Benzoquinone
16. 3.INCLUSION COMPLEXES/OCCLUSION COMPOUNDS:
One compound is trapped in lattice/cage like structure of other
compound. Interaction are due to suitable molecular structure.
A) CHANNEL LATTICE TYPE:
• In case of starch-iodine solution iodine molecule are trapped within
spiral of glucose molecule.
• In case of Urea-methyl α-lipolate is a needle shaped hexagonal
channel complex in which urea act as host.
Host (tubular channel)- Deoxycholic acid, urea, thiourea, amylose
Guest (long unbranched straight chain compounds)- paraffin, esters,
acids, ethanol.
Applications:
• Seperation of isomers:
Dextro, levo-terpineol are separated using Digitonin.
• In analysis of dermatological creams, long chain compounds
interfere and removed by complexation with urea.
17. B) LAYER TYPES:
• They form monomolecular layer of guest and host.
• Host (Layers With Gaps)- clays, bentonite
• Guest (entrapped in gaps)- hydrocarbons, alcohols, glycols.
• Use: Due to their large surface area they are used as
catalysts.
18. C)CLATHRATES: (cage like structure):
• During crystallization some compounds (host) form cage like
structures in which coordinating compound (guest) is entrapped.
• Ex: warfarin sodium (water + isopropyl alcohol)
• Ex. Hydroquinone form cage with hydrogen bonds and hole have
diameter of 4.2A0.This can entrap methanol, carbon dioxide,
hydrochloric acid.
CAGE
Application:
• Synthetic metal-alumino silicate are known to be used as
molecular sieves.
• These are use to store volatile substances and toxic substances.
19. D) MONO MOLECULAR INCLUSION COMPLEX:
Single guest molecule entrapped by single host molecule.(generally
cyclodextrins)
Cyclodextrins:
Cyclodextrins are cyclic oligo sacchirides containing minimum of 6 D-
(+) gluco pyranose units attached by α-1,4 linkages.
Cyclodextrins Cavity diameter (Ao) Glucopyranose units
α 5 6
β 6 7
γ 8 8
Hydrophilic
entrance
Hydrophobic
interior
21. Method of analysis:
Estimation of 2 parameters
1. Stoichiometric ratio of Ligand: Metal / Donar : Acceptor
2. Stability Constant of complex.
Methods:
1. Method of continuous variation.
2. Distribution method
3. Solubility method
4. pH titration method.
22. General procedure:
Equation for complexation
M + n A MAn
Stability constant
Applying Log on both sides
Log [MAn] = log K + log [M] + n log [A]
[M] = Conc. of Metal ion uncomplexed
[A] = Conc. of ligand uncomplexed
[MAn] = Conc. of complex
n = number of mole
23. 1. Method of continuous variation
1. Dielectric constant
2. Refractive index
3. Spectrophotometric
extinction coefficient
Physical
properties
Characteristics
of species.
A
+B
No
complexation
Complexatio
n
Physical
properties
are additive
values
Physical
properties
values different
24. 1. Due to
complexation
physical properties
result may be
maximum or
minimum.
2. At maximum/
minimum point note
concentration of
individual species.
3. Calculate
stoichiometric
ratio of species.
25. 2. Distribution method:
• Distribution of solute between two immiscible liquids is
expressed by Partition / Distribution coefficient.
• Partition coefficient / Distribution changes due to
complexation.
• By conducting 2 experiments stability constant is
estimated.
• Example: Iodine complex with Potassium iodide.
I2 + 𝐾+𝐼− = 𝐾+𝐼−3
26.
27. 3. Solubility method:
• When mixture form complexes solubility may increase/ decrease.
• Experiments are conducted to estimate donor – acceptor ratio and
equilibrium constant.
• Example: PABA-caffeine complex
Experiment:
1. Caffeine (Complexing agent) taken in different concentrations in a
series of flask.
2. Excess PABA is added to all flask with agitation
3. Solution are filtered and analyzed for drug content.
4. At zero conc. of caffeine the first point indicates solubility of drug
PABA in water.
5. With addition of caffeine the solubility of PABA is increased up to
second point. At this point the solution is saturated with respect to
complex and drug itself.
6. On further addition complex precipitate up to third point. Atthis
point all excess PABA converted to complex.
7. On further addition of caffeine higher complex are formed.
28.
29. 4. pH titration method:
This method is suitable if complexation produces change in pH.
Example: Chelation of cupric ions by glycine molecule
Chelation of calcium ion by EDTA
The reaction represented as
𝐶𝑢2+
+ 2𝑁𝐻3+
𝐶𝐻2𝐶𝑂𝑂−
= 𝐶𝑢 (𝑁𝐻2 𝐶𝐻2𝐶𝑂𝑂)2 + 2𝐻+
Experiment:
1. Glycine solution (75 ml) titrated with NaoH, pH is recorded.
2.Complex solution of Glycine solution (75 ml) and Cu+2 titrated
with NaoH, pH is recorded.
3.Complexation releases protons and pH decreases. Hence metal-
glycine complex curve below the glycine curve
4.The horizontal distance between the curve between the curve
gives amount of alkali cosumed.
5.Quantity of alkali = Concentration of ligand bound at that pH.
n= 𝑇𝑜𝑡𝑎𝑙 𝑐𝑜𝑛𝑐. 𝑜𝑓 𝑙𝑖𝑔𝑎𝑛𝑑 𝑏𝑜𝑢𝑛𝑑
𝑇𝑜𝑡𝑎𝑙 𝑐𝑜𝑛𝑐, 𝑜𝑓 𝑚𝑒𝑡𝑎𝑙 𝑖𝑜𝑛
30. Stability constant represented as β
log β = 2 X p [A] (at n=1)
p [A] = pKa- pH- log ( [HA]initial - [NaoH] )
Where p [A] is related to Conc. of ligand bound (glycine)
pKa = Dissociation constant of ligand, glycine
[HA]initial = Conc. of glycine at initial stage
[NaoH] = Horizontal distance expressed in mole/litre
31. COMPLEXATION –Applications in pharmacy
•Physical state
•Volatility
•Solid state Stability
•Chemical stability
•Solubility
•Dissolution
•Partition coefficient
•Absorption & bioavailability
•Reduced toxicity
•Antidote in metal poisoning
•Drug action through metal
poisoning
•Antibacterial activity
34. 7. Partition Coefficient:
(Water + Benzene) + Permanganate ions Partition in to
W
A
TER.
(Water + Benzene) + Permanganate ions + Crown ether
Partition in to Benzene.
8. Absorption & bioavailability
β-CD + Barbiturates Complex Improves
Bioavailability
Tetracyclines + Ca+2 / Mg+2 Insoluble metal Complex
Reduced Absorption & Bioavailability
9. Reduced Toxicity:
β-CD + Indomethacin Reduce ulcerogenic effect
β-CD + Chlorpramazine Reduce local tissue toxicity.
35. 10. Antidote in metal poisoning:
Arsenic, Mercury (Toxic metal ions) + (-SH) groups of
enzymes Effect normal functioning.
Dimercaprol + Arsenic, Complex Easily eliminated
Mercury from body.
11. Drug action through metal poisoning:
8-Hydroxy Quinoline + Iron Complex Enter malarial
parasite Accumulation of metal Anti-Malarial action.
12. Antibacterial activity:
PAS + Cupric ions Cupric Complex + Chelates.
(anti-Tubercular drug)
Chelates 30 times more fat soluble Penetrate in to
cells High anti-Tubercular action.
36. PROTEIN DRUG COMPLEXATION AND DRUG
ACTION
• The phenomenon of complex formation of drugs with
proteins is called protein binding.
• A protein bound drug is neither metabolized nor excreted
hence it is pharmacologically inactive. Binding of drugs to
proteins is generally of reversible & irreversible.
• Reversible binding generally involves weak chemical bond
such as: Hydrogen bonds, Hydrophobic bonds, Ionic bonds
and Van der waal's forces.
• While Irreversible drug binding, though rare, arises as a
result of covalent binding and is often result carcinogenicity
or tissue toxicity of the drug.
Protein + drug ⇌Protein-drug complex
Protein binding may be divided into:
1. Intracellular binding.
2. Extracellular binding.
37.
38. BINDING OF DRUG TO BLOOD COMPONENTS
The order of binding of drugs:
albumin> α1-acid glycoprotein> lipoproteins> globulins
39. Binding of drug to Human serum albumin:
• The Molecular weight of albumin is 65,000 — 69,000.Albumin
is distributed in the plasma and in the extracellular fluids of
skin , muscle ,and various tissues.
• Elimination half life of albumin is 17-18 days . Albumin
concentration is 3.5-5.5% (w/v) or 4.5 mg/dl.
• Many weak acidic drugs bind to albumin by electrostatic and
hydrophobic bonds.
• There are four site of attachment of drug.
I. Warfarine & Azapropazone Site
II. Diazepam Site
III. Digoxine Site
IV. Tamoxifen Site
40. SITE l: To this specific site a large population of drugs bind like Non-
Steroidal AntiInflammatory Drugs mainly phenylbutazone,
indomethacin, many sulfonamides e.g.; sulfamethoxine,
sulfamethizole, and even many anti-epileptic drugs like phenytoin
etc. This site is also called as Warfarin binding site or as
Azapropazone binding site.
SITE Il: This is actually said to be Diazepam binding site.
Benzodiazepines, medium chain fatty acids, ibuprofen, ketoprofen,
etc. bind extensively at this site. This is due to structural changes the
following drugs have high and specific affinity for this site.
SITE Ill: This site is called as Digitoxin binding site
SITE IV: This is referred as Tamoxifen binding site.
41. Binding of drug to α1-acid glycoprotein
They ate also called as orosomucoid. The molecular weight of α1-
acid glycoprotein is 44,000. They are bound by Hydrophobic bonds
E.g. : Basic Drugs such as Imipramine , Amytriptyline , Lidocaine ,
nortriptyline, Propranolol, Quinidine and disopyramide
Binding of drug to Lipoprotines:
They are bound by hydrophobic bond. The molecular weight of
lipoprotein is 2-3 lakhs to 34 lakhs. Bound drug dissolve in lipid
core. Example acidic drug (diclofenac), Neutral (cyclosporin) and
Basic drug (chlorpromazine). They are classified as
• Chylomicrons
• Very low density lipoprotine
• Low density lipoprotine(more in human)
• High density lipoprotine
42.
43. Binding Of Drugs To Blood cells
Red Blood Cells (RBC's) are the major blood cells which rates
about 40% of total blood. The red blood corpuscles constitute
95% of the total blood cells concentration in the body. Major
portion of red blood cells to which drugs can bind are:
i) Hemoglobin: The weight & structural is similar to that of
HSA but the concentration is much higher than of albumins in
blood. Examples of drugs that bind are phenytoin,
pentobarbital etc.
ii) Carbonic Anhydrase Inhibitors: Carbonic anhydrase
inhibitors mainly bind to the site like chlorthaizine.
iii) Red Blood cell membrane: Basic drugs like imipramine are
known to bind to RBC membrane.
44. BINDING OF DRUG TO EXTRAVASCULAR TISSUE PROTEIN
•
• Importance: 1. It increases apparent volume of distribution of drug.
2. localization of a drug at a specific site in body.
• Factor affecting: lipophilicity, structural feature of drug, perfusion
rate, pH differences.
Binding order: Liver › Kidney › Lung ›Muscles
Tissue Binding of
1.Liver Irreversible binding of Epoxides of
Halogenated Hydrocarbon & Paracetamol.
2.Lungs Basic drugs: Imipramine, Chlorpromazine,
&AntiHistaminics.
45. Tissue Binding of
3.Kidney Metallothionin protein binds to Heavy
metals & results in Renal accumulation
and toxicity.
4.Skin Chloroquine& Phenothiazine bind
to Melanin.
5.Eye Chloroquine & Phenothiazine also
binds to Eye Melanin & results in
Retinopathy.
6.Hairs Arsenicals, Chloroquine, &
Phenothiazine.
7.Bones Tetracycline(yellow discoloration of
teeth), Lead(replaces Ca & cause
brittleness)
8.Fats Lipophilic drugs
(thiopental), Pesticides
(DDT)
9.NucleicAcid Chloroquine & Quinacrine.
46. FACTORS AFFECTING PROTEIN DRUG BINDING
1. Drug-related factors
a. Physicochemical characteristics of the drug:-
Protein binding is directly related to the lopophilicity of drug. An increase
in lipophilicity increases the extent of binding.
b. Concentration of drug in the body:-
Alteration in the concentration of drug substance as well as the protein
molecules or surfaces subsequently brings alteration in the protein
binding process.
c. Affinity of a drug for a particular bindingcomponent:-
This factor entirely depends upon the degree of attraction or affinity the
protein molecule or tissues have towards drug moieties. For Digoxin has
more affinity for cardiac muscles proteins as compared to that of
proteins of skeletal muscles or those in the plasma like HSA.
47. 2. Protein/ tissue related factors:
a. Physicochemical characteristics of protein or binding agent:
•. Lipoproteins & adipose tissue tend to bind lipophilic drug by
dissolving them in their lipid core.
•. The physiological pH determines the presence of active anionic &
cationic groups on the albumin to bind a variety of drug.
b. Concentration of protein or binding component:
•. Among the plasma protein , binding predominantly occurs with
albumin, as it is present in high concentration in comparision to
other plasma protein.
•. The amount of several proteins and tissue components available for
binding, changes during disease state.
48. 3. Drug interactions
a. Competition between drugs for the binding sites :-
D2
D1+P D2+P
D1: Displaced drug. D2: Displacer drug.
e.g. Administration of phenylbutazone to a patient on Warfarin therapy
results in Hemorrhagic reaction.
b. Competition between drug & normal body constituents:-
The free fatty acids are known to interact with a no. of drugs that binds
primarily to HSA. the free fatty acid level increase in physiological, pathological
condition.
49. c. Allosteric changes in protein molecule:-
• The process involves alteration of the protein structure by the drug
or it’s metabolite thereby modifying its binding capacity.
e.g. aspirin acetylates lysine fraction of albumin thereby modifying its
capacity to bind NSAIDs like phenylbutazone.
4. Patient-related factors
Age:
1.Neonates: Low albumin content: More free drug.
2.Young infants: High dose of Digoxin due to large renal
clearance.
3.Elderly:Low albumin: So more free drug.
Intersubject variability: Due to genetics & environmental factors.
50. Disease states:-
Disease Influence on plasma
protein
Influence on protein drug
binding
Renal failure ↓ Albumin content ↓ binding of acidic drugs;
neutral and basic drugs are
un affected
Hepatic failure ↓ Albumin synthesis ↓ binding of acidic drugs;
and binding of basic drugs is
normal
Inflamatory states i.e,truama
surgery etc… ↑AAG levels
↑ binding of basic drugs;
neutral and acidic drugs are
un affected
52. A scatchard plot is useful when high conc. of free drug is there.
53.
54.
55. SIGNIFICANCE OF PROTEIN/TISSUE BINDING OF DRUG
a. Absorption-
• As we know the conventional dosage form follow first order kinetics.
So when there is more protein binding then it disturbs the absorption
equilibrium.
b. Distribution-
• A protein bound drug in particular does not cross the BBB, the
placental barrier, the glomerulus.
• Thus protein binding increases the distribution of drugs.
c. Metabolism-
• Protein binding decreases the metabolism of drugs & enhances the
biological half life.
• Only unbound fraction get metabolized.
• e.g. Phenylbutazone & Sulfonamide.
56. d. Elimination
•
•
•
Only the unbound drug is capable of being eliminated.
Protein binding prevent the entry of drug to the metabolizing organ
(liver ) & to glomerulus filtration.
e.g. Tetracycline is eliminated mainly by glomerular filtration.
e. Systemic solubility of drug
• Lipoprotein act as vehicle for hydrophobic drugs like steroids, heparin
etc.
f. Drug action-
• Protein binding inactivates the drugs because sufficient concentration of
drug can not be build up in the receptor site for action.
• e.g. Naphthoquinone
57. g. Sustain release-
• The complex of drug protein in the blood act as a reservoir &
continuously supply the free drug.
• e.g. Suramin sodium-protein binding for antitrypanosomal action.
h. Diagnosis-
• The chlorine atom of chloroquine replaced with radiolabeled I-
131 can be used to visualize-melanomas of eye & disorders of
thyroid gland.
58. THERMODYNAMIC TREATMENT OF STABILITY CONSTANTS:
• The standard free energy change of complexation is related to the
overall stability constant K (or any of the formation constants) by
the relationship.
ΠGo = -2.303RT log K
• The standard enthalpy change ΠH may be obtained from the slope
of a plot of log K versus l/T, following the expression:
log K = ΠH / 2.303R T + constant
• When the values of K at two temperatures are known, the
following equation may be 'used:
log(K2/K1 ) = - ΠH/2.303R(T2-T1/T1-T2)
• The standard entropy change is :
ΠGo = ΠH – T ΠS
• Andrews and Keefer demonstrated that ΠH andΠS generally
become more negative as the stability constant for molecular
complexation increases.
• As the binding between donor and acceptor becomes stronger, ΠH
would be expected to have a larger negative value.