1)Physical Properties
Physical property of drug is responsible for its action
2)Chemical Properties
The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
This document discusses structure-activity relationships in drug design and formulation. It introduces Hammett and Hansch plots, which relate reaction rates and biological activity to electronic and physicochemical properties. Modification of lead compounds is explored through changing functional groups, stereochemistry and lipophilicity. Morphine is used as a case study to illustrate how properties like log P, binding groups and stereochemistry impact opioid activity. The conclusion emphasizes the role of medicinal chemistry in understanding disease and developing safer, more effective pharmaceuticals.
This document discusses acid-base theories and the ionization constant (pKa). The Arrhenius, Bronsted-Lowry, and Lewis theories define acids and bases. The pKa describes the tendency of compounds to dissociate into ions and is related to pH. The Henderson-Hasselbalch equation relates pH, pKa, and the concentrations of ionized and unionized forms of an acid or base. Determining a drug's pKa is important for understanding its absorption, distribution, and effects in different parts of the body which have varying pH levels.
Phsicochemical properties according to pci syllubus.
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties : Physical property of drug is responsible for its action
2)Chemical Properties :The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
Medicinal chemistry involves the design and synthesis of pharmaceutical agents to benefit humanity. It includes synthesis, structure-activity relationship studies, receptor interactions, and analysis of absorption, distribution, metabolism, and excretion. The field has its roots in the isolation of alkaloids like morphine in the early 19th century. In the late 19th century, semi-synthetic and synthetic derivatives of plant-derived compounds were developed. Modern medicinal chemistry emerged in the late 19th/early 20th century with advances like the receptor theory and development of antibiotics and sulfonamides. The 1940s-1960s were a "golden era" with the invention of many modern drug classes such as corticosteroids, antipsychotics
Protein binding of drugs can be reversible or irreversible. Reversible binding involves weak interactions like hydrogen bonds or hydrophobic bonds, while irreversible binding results from covalent bonds. Drugs bind to plasma proteins like albumin and alpha-1-acid glycoprotein, as well as to components in blood cells and extravascular tissues. The extent of protein binding affects the absorption, distribution, metabolism, and excretion of drugs. It determines the amount of active, unbound drug available to elicit its pharmacological response. Protein binding is influenced by factors related to the drug, binding proteins, and patient characteristics. It is important for understanding a drug's pharmacokinetics and pharmacodynamics.
Drug-plasma protein binding plays a key role in drug pharmacokinetics and pharmacodynamics. Proteins, particularly albumin and alpha-1-acid glycoprotein, bind drugs reversibly through mechanisms like hydrogen bonding, hydrophobic interactions, and van der Waals forces. Only the unbound fraction of a drug is active, as protein-bound drug is inert and cannot cross membranes or exert effects. Several factors influence protein binding, including drug properties, protein concentrations, and disease states. The degree of protein binding impacts drug absorption, distribution, metabolism, and elimination.
1 UNIT I: INTRODUCTION TO MEDICINAL CHEMISTRY SONALI PAWAR
Medicinal chemistry is a multidisciplinary field that combines organic chemistry, biochemistry, pharmacology and other sciences to study the design, synthesis and actions of pharmaceutical drugs. The document provides a brief history of medicinal chemistry, noting early examples of medicinal substances used in ancient civilizations. It then discusses several important physicochemical properties that influence a drug's biological effects, including solubility, partition coefficient, hydrogen bonding, ionization and others. The relationships between these properties and drug absorption, distribution, metabolism and excretion are also summarized.
This document discusses structure-activity relationships in drug design and formulation. It introduces Hammett and Hansch plots, which relate reaction rates and biological activity to electronic and physicochemical properties. Modification of lead compounds is explored through changing functional groups, stereochemistry and lipophilicity. Morphine is used as a case study to illustrate how properties like log P, binding groups and stereochemistry impact opioid activity. The conclusion emphasizes the role of medicinal chemistry in understanding disease and developing safer, more effective pharmaceuticals.
This document discusses acid-base theories and the ionization constant (pKa). The Arrhenius, Bronsted-Lowry, and Lewis theories define acids and bases. The pKa describes the tendency of compounds to dissociate into ions and is related to pH. The Henderson-Hasselbalch equation relates pH, pKa, and the concentrations of ionized and unionized forms of an acid or base. Determining a drug's pKa is important for understanding its absorption, distribution, and effects in different parts of the body which have varying pH levels.
Phsicochemical properties according to pci syllubus.
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties : Physical property of drug is responsible for its action
2)Chemical Properties :The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
Medicinal chemistry involves the design and synthesis of pharmaceutical agents to benefit humanity. It includes synthesis, structure-activity relationship studies, receptor interactions, and analysis of absorption, distribution, metabolism, and excretion. The field has its roots in the isolation of alkaloids like morphine in the early 19th century. In the late 19th century, semi-synthetic and synthetic derivatives of plant-derived compounds were developed. Modern medicinal chemistry emerged in the late 19th/early 20th century with advances like the receptor theory and development of antibiotics and sulfonamides. The 1940s-1960s were a "golden era" with the invention of many modern drug classes such as corticosteroids, antipsychotics
Protein binding of drugs can be reversible or irreversible. Reversible binding involves weak interactions like hydrogen bonds or hydrophobic bonds, while irreversible binding results from covalent bonds. Drugs bind to plasma proteins like albumin and alpha-1-acid glycoprotein, as well as to components in blood cells and extravascular tissues. The extent of protein binding affects the absorption, distribution, metabolism, and excretion of drugs. It determines the amount of active, unbound drug available to elicit its pharmacological response. Protein binding is influenced by factors related to the drug, binding proteins, and patient characteristics. It is important for understanding a drug's pharmacokinetics and pharmacodynamics.
Drug-plasma protein binding plays a key role in drug pharmacokinetics and pharmacodynamics. Proteins, particularly albumin and alpha-1-acid glycoprotein, bind drugs reversibly through mechanisms like hydrogen bonding, hydrophobic interactions, and van der Waals forces. Only the unbound fraction of a drug is active, as protein-bound drug is inert and cannot cross membranes or exert effects. Several factors influence protein binding, including drug properties, protein concentrations, and disease states. The degree of protein binding impacts drug absorption, distribution, metabolism, and elimination.
1 UNIT I: INTRODUCTION TO MEDICINAL CHEMISTRY SONALI PAWAR
Medicinal chemistry is a multidisciplinary field that combines organic chemistry, biochemistry, pharmacology and other sciences to study the design, synthesis and actions of pharmaceutical drugs. The document provides a brief history of medicinal chemistry, noting early examples of medicinal substances used in ancient civilizations. It then discusses several important physicochemical properties that influence a drug's biological effects, including solubility, partition coefficient, hydrogen bonding, ionization and others. The relationships between these properties and drug absorption, distribution, metabolism and excretion are also summarized.
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.
DEFINITION:
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties
Physical property of drug is responsible for its action 2)Chemical Properties
The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
Various Physico-Chemical Properties are,
Solubility Partition Coefficient
Dissociation constant Hydrogen Bonding Ionization of Drug Redox Potential Complexation Surface activity Protein binding Isosterism
1. Solubility:
• The solubility of a substance at a given temperature is defined as the concentration of the dissolved solute, which is in equillibrium with the solid solute.
• Solubility depends on the nature of solute and solvent as well as temperature , pH & pressure.
• The solubility of drug may be expressed in terms of its affinity/philicity or repulsion/phobicity for either an aqueous or organic solvent.
The atoms and molecules of all organic substances are held together by various types of bonds (e.g. hydrogen bond, dipole –dipole, ionic bond etc.)
These forces are involved in solubility because it is the solvent-solvent, solute-solute, solvent-solute interactions that governs solubility.
Methods to improve solubility of drugs
1) Structural modification (alter the structure of molecules) 2) Use of Cosolvents (Ethanol, sorbitol,PPG,PEG)
3) Employing surfactants 4) Complexation
Importance of solubility
1. Solubility concept is important to pharmacist because it govern the preparation of liquid dosage form and the drug must be in solution before it is absorbed by the body to produce the biological activity.
2. Drug must be in solution form to interact with receptors.
The movement of molecules from one phase to another is called partitioning.
If two immiscible phases are placed adjacent to each other, the solute will distribute itself between two immiscible phases until equilibrium is attained; therefore no further transfer of solute occurs.
1. Metabolism, or biotransformation, is the process by which enzymes convert lipid-soluble compounds into water-soluble compounds so they can be excreted from the body.
2. The major site of drug metabolism is the liver, through phase I (functionalization) and phase II (conjugation) reactions. Phase I reactions involve oxidation, reduction, and hydrolysis, while phase II reactions conjugate compounds to make them more hydrophilic through glucuronidation, methylation, sulfation, and other processes.
3. Cytochrome P450 enzymes and UDP-glucuronyl transferases are among the most important enzyme families involved in drug metabolism. Metabolism can
Protein binding of drugs can significantly impact a drug's pharmacokinetic and pharmacodynamic properties. There are two main classes of protein binding - binding to blood components like plasma proteins and blood cells, and binding to extravascular tissue proteins in organs like the liver, kidneys, lungs, and muscles. The extent of protein binding is influenced by factors related to the drug, such as its lipophilicity and concentration, factors related to the binding protein, such as its concentration and number of binding sites, and patient-related factors like age and disease state. Protein binding impacts a drug's absorption, distribution, metabolism, elimination, and ability to reach its receptor site and produce an effect. It can inactivate drugs by sequestering
Medicinal chemistry involves the design and discovery of biologically active compounds to treat diseases. A drug's effects depend on its physicochemical properties like ionization, polarity, and lipid-water partition coefficient, which determine absorption, distribution, metabolism, and excretion. Drug names include chemical, trade, and generic names. Understanding a drug's physicochemical parameters helps explain its mechanism of action and effects.
Bioisosterism is a strategy used in drug design that involves replacing one chemical group with another that has similar physical or chemical properties. This is done to improve properties like potency, selectivity, toxicity, and pharmacokinetics without significantly changing the chemical structure. Common bioisosteric replacements include replacing hydrogen with fluorine, replacing carboxylic acids with amides or esters, or replacing phenyl rings with heteroaromatic or saturated rings. The application of bioisosterism has been an important concept in medicinal chemistry for nearly 80 years and will continue to play a role in drug discovery and optimization.
Pharmaceutical suspension can be classified based on the dispersed phase, vehicle used, proportion of solid particles, particle size, etc. They can be stabilized using suspending agents, viscosity increasing agents, surface charge, etc. Recent advances include nano suspensions to improve solubility, taste masked suspensions to improve palatability, and sustained release suspensions to reduce dosing frequency. Evaluation methods include sedimentation studies, rheological measurements, and zeta potential determination.
This is the presentation for B. Pharm. IV semester students.
It includes Introduction of Medicinal Chemistry, History and Development of Medicinal Chemistry
This powerpoint presentation will help to know about introduction of bioisosterism by Biotechnology point of view. Hope this powerpoint presentation will your reference.
Polymorphism is the ability of solid materials to exist in two or more crystalline forms with different arrangements or conformations of the constituents in the crystal lattice. ... More than 50% of active pharmaceutical ingredients (APIs) are estimated to have more than one polymorphic form
This document discusses cytochrome P450 (CYP) enzymes, which metabolize many drugs and are primarily located in hepatocyte endoplasmic reticulum. It describes the three types of enzyme inhibition - competitive, non-competitive, and uncompetitive. Several examples of drug interactions caused by CYP inhibition are provided, including interactions between terfenadine and macrolides/azole antifungals, cimetidine and disopyramide, grapefruit juice and calcium channel blockers, omeprazole and phenytoin/diazepam, and rifampicin induction of CYP enzymes.
Surfactants and their applications in pharmaceutical dosage formMuhammad Jamal
This presentation is very much helpful for the medical students,pharmacists, researchers and other health care providers. i hope it will provide important information regarding surfactants and their applications in pharmaceutical dosage forms.
Medicinal chemistry involves the discovery and design of new therapeutic chemicals and their development into medicines and drugs. It is an interdisciplinary field combining chemistry and biology. Medicinal chemists work to design new drug compounds, determine their biological effects, optimize their structures for desired effects and minimal side effects, and study how the body processes drugs. The physicochemical properties of drugs, like solubility, acidity, and reactivity influence their biological actions and interactions with targets in the body. Understanding these properties helps predict drugs' behaviors and design new candidates. A drug's solubility is key to its formulation and absorption in the body. Both lipophilic and hydrophilic structural features impact a molecule's solubility profile. Acidity and
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.
Medicinal chemistry involves the design and synthesis of pharmaceutical agents to benefit humanity. It includes structure-activity relationships, receptor interactions, and absorption/metabolism properties of compounds. Combinatorial chemistry produces large libraries of similar molecules for screening via techniques like solid phase synthesis and parallel/mixed synthesis. Quantitative structure-activity relationship analysis uses parameters like lipophilicity, electronic effects, and steric hindrance to develop mathematical models correlating biological activity to a compound's physicochemical properties.
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties : Physical property of drug is responsible for its action
2)Chemical Properties :The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
The document discusses various physicochemical properties of drugs that influence their biological activity and effects. It covers properties like solubility, partition coefficient, dissociation constant, hydrogen bonding, ionization, complexation, and stereochemistry. Solubility and partition coefficient affect absorption and distribution of drugs in the body. Ionization influences what form a drug is in and its ability to cross membranes. Hydrogen bonding and complexation can impact properties like boiling point and drug availability. Protein binding and stereochemistry also influence a drug's pharmacological effects. Understanding these physicochemical properties is important for drug design and development.
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.
DEFINITION:
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties
Physical property of drug is responsible for its action 2)Chemical Properties
The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
Various Physico-Chemical Properties are,
Solubility Partition Coefficient
Dissociation constant Hydrogen Bonding Ionization of Drug Redox Potential Complexation Surface activity Protein binding Isosterism
1. Solubility:
• The solubility of a substance at a given temperature is defined as the concentration of the dissolved solute, which is in equillibrium with the solid solute.
• Solubility depends on the nature of solute and solvent as well as temperature , pH & pressure.
• The solubility of drug may be expressed in terms of its affinity/philicity or repulsion/phobicity for either an aqueous or organic solvent.
The atoms and molecules of all organic substances are held together by various types of bonds (e.g. hydrogen bond, dipole –dipole, ionic bond etc.)
These forces are involved in solubility because it is the solvent-solvent, solute-solute, solvent-solute interactions that governs solubility.
Methods to improve solubility of drugs
1) Structural modification (alter the structure of molecules) 2) Use of Cosolvents (Ethanol, sorbitol,PPG,PEG)
3) Employing surfactants 4) Complexation
Importance of solubility
1. Solubility concept is important to pharmacist because it govern the preparation of liquid dosage form and the drug must be in solution before it is absorbed by the body to produce the biological activity.
2. Drug must be in solution form to interact with receptors.
The movement of molecules from one phase to another is called partitioning.
If two immiscible phases are placed adjacent to each other, the solute will distribute itself between two immiscible phases until equilibrium is attained; therefore no further transfer of solute occurs.
1. Metabolism, or biotransformation, is the process by which enzymes convert lipid-soluble compounds into water-soluble compounds so they can be excreted from the body.
2. The major site of drug metabolism is the liver, through phase I (functionalization) and phase II (conjugation) reactions. Phase I reactions involve oxidation, reduction, and hydrolysis, while phase II reactions conjugate compounds to make them more hydrophilic through glucuronidation, methylation, sulfation, and other processes.
3. Cytochrome P450 enzymes and UDP-glucuronyl transferases are among the most important enzyme families involved in drug metabolism. Metabolism can
Protein binding of drugs can significantly impact a drug's pharmacokinetic and pharmacodynamic properties. There are two main classes of protein binding - binding to blood components like plasma proteins and blood cells, and binding to extravascular tissue proteins in organs like the liver, kidneys, lungs, and muscles. The extent of protein binding is influenced by factors related to the drug, such as its lipophilicity and concentration, factors related to the binding protein, such as its concentration and number of binding sites, and patient-related factors like age and disease state. Protein binding impacts a drug's absorption, distribution, metabolism, elimination, and ability to reach its receptor site and produce an effect. It can inactivate drugs by sequestering
Medicinal chemistry involves the design and discovery of biologically active compounds to treat diseases. A drug's effects depend on its physicochemical properties like ionization, polarity, and lipid-water partition coefficient, which determine absorption, distribution, metabolism, and excretion. Drug names include chemical, trade, and generic names. Understanding a drug's physicochemical parameters helps explain its mechanism of action and effects.
Bioisosterism is a strategy used in drug design that involves replacing one chemical group with another that has similar physical or chemical properties. This is done to improve properties like potency, selectivity, toxicity, and pharmacokinetics without significantly changing the chemical structure. Common bioisosteric replacements include replacing hydrogen with fluorine, replacing carboxylic acids with amides or esters, or replacing phenyl rings with heteroaromatic or saturated rings. The application of bioisosterism has been an important concept in medicinal chemistry for nearly 80 years and will continue to play a role in drug discovery and optimization.
Pharmaceutical suspension can be classified based on the dispersed phase, vehicle used, proportion of solid particles, particle size, etc. They can be stabilized using suspending agents, viscosity increasing agents, surface charge, etc. Recent advances include nano suspensions to improve solubility, taste masked suspensions to improve palatability, and sustained release suspensions to reduce dosing frequency. Evaluation methods include sedimentation studies, rheological measurements, and zeta potential determination.
This is the presentation for B. Pharm. IV semester students.
It includes Introduction of Medicinal Chemistry, History and Development of Medicinal Chemistry
This powerpoint presentation will help to know about introduction of bioisosterism by Biotechnology point of view. Hope this powerpoint presentation will your reference.
Polymorphism is the ability of solid materials to exist in two or more crystalline forms with different arrangements or conformations of the constituents in the crystal lattice. ... More than 50% of active pharmaceutical ingredients (APIs) are estimated to have more than one polymorphic form
This document discusses cytochrome P450 (CYP) enzymes, which metabolize many drugs and are primarily located in hepatocyte endoplasmic reticulum. It describes the three types of enzyme inhibition - competitive, non-competitive, and uncompetitive. Several examples of drug interactions caused by CYP inhibition are provided, including interactions between terfenadine and macrolides/azole antifungals, cimetidine and disopyramide, grapefruit juice and calcium channel blockers, omeprazole and phenytoin/diazepam, and rifampicin induction of CYP enzymes.
Surfactants and their applications in pharmaceutical dosage formMuhammad Jamal
This presentation is very much helpful for the medical students,pharmacists, researchers and other health care providers. i hope it will provide important information regarding surfactants and their applications in pharmaceutical dosage forms.
Medicinal chemistry involves the discovery and design of new therapeutic chemicals and their development into medicines and drugs. It is an interdisciplinary field combining chemistry and biology. Medicinal chemists work to design new drug compounds, determine their biological effects, optimize their structures for desired effects and minimal side effects, and study how the body processes drugs. The physicochemical properties of drugs, like solubility, acidity, and reactivity influence their biological actions and interactions with targets in the body. Understanding these properties helps predict drugs' behaviors and design new candidates. A drug's solubility is key to its formulation and absorption in the body. Both lipophilic and hydrophilic structural features impact a molecule's solubility profile. Acidity and
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.
Medicinal chemistry involves the design and synthesis of pharmaceutical agents to benefit humanity. It includes structure-activity relationships, receptor interactions, and absorption/metabolism properties of compounds. Combinatorial chemistry produces large libraries of similar molecules for screening via techniques like solid phase synthesis and parallel/mixed synthesis. Quantitative structure-activity relationship analysis uses parameters like lipophilicity, electronic effects, and steric hindrance to develop mathematical models correlating biological activity to a compound's physicochemical properties.
The ability of a chemical compound to elicit a pharmacological/ therapeutic effect is related to the influence of various physical and chemical (physicochemical) properties of the chemical substance on the bio molecule that it interacts with.
1)Physical Properties : Physical property of drug is responsible for its action
2)Chemical Properties :The drug react extracellularly according to simple chemical reactions like neutralization, chelation, oxidation etc.
The document discusses various physicochemical properties of drugs that influence their biological activity and effects. It covers properties like solubility, partition coefficient, dissociation constant, hydrogen bonding, ionization, complexation, and stereochemistry. Solubility and partition coefficient affect absorption and distribution of drugs in the body. Ionization influences what form a drug is in and its ability to cross membranes. Hydrogen bonding and complexation can impact properties like boiling point and drug availability. Protein binding and stereochemistry also influence a drug's pharmacological effects. Understanding these physicochemical properties is important for drug design and development.
Physicochemical parameters in relation to Biological activitiesSKarthigaSVCP
This document discusses various physicochemical parameters that influence drug solubility, ionization, and biological activity. It defines key concepts like solubility, partition coefficient, ionization, protein binding, hydrogen bonding, and stereochemistry. Solubility depends on interactions between solute and solvent properties. Partition coefficient indicates how drugs distribute between aqueous and lipid phases. Ionization influences whether drugs are charged or uncharged. Protein binding, hydrogen bonding, and complexation impact how drugs interact with biological targets and receptors. Stereochemistry, including conformational, optical, and geometrical isomers, also influences pharmacological properties and effects. Understanding these physicochemical parameters is important for drug design and development.
Physico-chemical Properties in Relation of Drug actionPradnya Gondane
This is the presentation for B. Pharm. IV semester students. It includes all the physico-chemical properties which affect drug action like solubility, ionization, pH, pKa, Protein Binding, Chelation, Hydrogen Bonding, Partition Coefficient and steric factors which includes, optical, conformational and bio isosters. This is prepared according to the PCI syllabus for B. Pharm. IV Semester students for Subject Medicinal Chemistry-I
The document provides an overview of preformulation studies, which are conducted to determine the physicochemical properties of new drug substances prior to formulation development. Key aspects covered include definition of preformulation, factors considered, objectives, outcomes, common tests like solubility and stability studies, and techniques involved. Specifically, the document discusses solubility analysis methods, factors affecting solubility like pH and temperature, and importance of solubility determination. It also covers common degradation pathways like oxidation and hydrolysis, and approaches to prevent or minimize degradation.
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.
1) Preformulation solubility studies focus on understanding a drug candidate's solubility profile and solubilization mechanisms to provide a basis for later formulation work. Key factors studied include pH, temperature, ionic strength, and buffer concentrations.
2) Analytical methods like HPLC, UV/visible spectroscopy, and gas chromatography are useful for solubility measurements. Determining a drug's pKa is also important to understand how solubility may change with pH.
3) Temperature, pH, common ion effects, and cosolvents can all impact a drug's solubility and dissolution rate, which are important considerations for bioavailability.
This document discusses the physicochemical properties of drug molecules that influence drug kinetics and performance. It covers properties like ionization, partition coefficients, solubility, and polymorphism. Ionization affects drug absorption, binding and elimination based on a drug's pKa and the pH. Partition coefficients influence membrane permeability. Solubility and polymorphic forms impact oral absorption. Other properties like hygroscopicity, surface activity, and ability to form hydrogen bonds or chelates also influence drug behavior in the body. Steric features like conformational isomers and optical isomers can determine a drug's specificity for receptor binding and pharmacological effects.
Physico chemical properties of drugs-convertedN J V S Pavan
this presentation is about the physico-chemical properties of a drug which are the reason for the drug's therapeutic effects and pharmacokinetics , pharmacodynamics ...
the information in the presentation is very much useful for the b.pharm 4th sem students .
Students can easily understand the concept as the presentation contains many examples
The document discusses preformulation studies that are conducted prior to developing a dosage form for a new drug. The objectives are to determine the drug's physicochemical properties, solubility, stability, and compatibility with excipients. Key tests include solubility studies under various conditions, stability studies of solid and liquid states under stress conditions like heat, light and pH, and chemical characterization of properties like oxidation and hydrolysis. The outcomes aim to develop a formulation that safely delivers the drug to the site of action as intended.
PHYSICOCHEMICAL PROPERTIES OF DRUG MOLECU;E.pptxbreenaawan
This document discusses various physicochemical properties of drug molecules that influence their absorption and activity. It defines properties like ionization, partition coefficients, solubility, and polymorphism. It explains how these properties impact absorption in the gastrointestinal tract and interaction with targets. Factors like pH, buffers, and functional groups are described as influencing whether a drug is in an ionized or un-ionized form. The relationships between these physicochemical characteristics and a drug's behavior provide a framework for understanding drug activity.
Drug stability consideration and degradationJalal Uddin
This document discusses drug stability and factors that affect it. It defines drug stability as the ability of a drug formulation to remain within specified chemical, microbiological, therapeutic, physical and toxicological limits over a period of time. The main factors that can affect drug stability are pH, temperature, moisture, light, oxygen, and additives. Common types of drug degradation include hydrolysis, oxidation, photolysis, and isomerization. Proper packaging, inclusion of antioxidants and buffers, and controlling environmental conditions like temperature and humidity can help protect drugs and increase their shelf life.
This document discusses preformulation, which involves characterizing the physical and chemical properties of a new drug substance to develop a stable, safe, and effective dosage form. The goals are to establish properties like solubility, stability, and kinetics. Key aspects covered include solubility analysis, partition coefficient, chemical stability studies like hydrolysis and oxidation, polymorphism, and particle size analysis. Understanding these characteristics is essential for rational dosage form development and selection.
The document discusses preformulation of sterile products. It covers key areas of preformulation including bulk characterization, solubility analysis, and stability analysis. Bulk characterization involves assessing properties like crystallinity, polymorphism, particle size, powder flow, and hygroscopicity. Solubility analysis includes studying aqueous solubility, drug ionization at physiological pH, partition coefficient, and thermal effects. Stability analysis focuses on stability in toxicology formulations, solution stability, and solid state stability under various conditions. The goal of preformulation is to characterize important physicochemical properties of drug substances to aid in developing appropriate formulations.
The document discusses the pH partition hypothesis, which states that the absorption of drugs across biomembranes is governed by the drug's dissociation constant (pKa), lipid solubility of the un-ionized form, and the pH of the absorption site. According to the hypothesis, only the un-ionized form of an acid or base drug can be absorbed if it is sufficiently lipid soluble. The fraction of a drug in its un-ionized form can be calculated using the Henderson-Hasselbach equation based on the drug's pKa and the pH. However, the pH partition theory is an oversimplification and does not always accurately predict drug absorption behavior.
This document provides an overview of preformulation studies, which characterize the physical and chemical properties of new drug molecules to aid in the development of safe, effective, and stable dosage forms. Some key points covered include:
- Preformulation studies give direction for dosage form selection, excipient choice, composition, and process development.
- Important physicochemical properties to determine include solubility, partition coefficient, pKa, stability, and interactions with excipients.
- Methods are described for evaluating properties like solubility, dissolution, oxidation, hydrolysis, and polymorphism which can impact stability and bioavailability.
- Understanding these properties aids in developing robust formulations and setting appropriate storage conditions for drug products
This document discusses drug stability and degradation. It begins with an introduction defining drug stability and the various types including chemical, physical, therapeutic, toxicological, and microbiological. It then covers the main chemical degradation routes of drugs including hydrolysis, oxidation, decarboxylation, dehydration, and photodegradation. Several examples are provided for each. Environmental and formulation factors that can influence drug stability are also outlined. Finally, various strategies for drug stabilization are presented such as temperature control, light protection, and use of antioxidants or chelating agents.
Drug stability studies are important to ensure uniform dosage throughout a drug's shelf life. There are various routes of drug degradation including hydrolysis, oxidation, and racemization. Hydrolysis can occur via cleavage of ester or amide bonds in the drug. Oxidation is caused by reaction with oxygen and is catalyzed by metals, pH, and solvents. Racemization involves the loss of optical activity in chiral drugs. Stability can be improved by controlling pH, antioxidants, chelating agents, and solvents used.
U.S.F.D.A. was the pioneer in the concept of process validation.
Validation had proven to be an important tool for quality management of pharmaceutical according to ISO 9000:2000.
U.S.F.D.A. was the pioneer in the concept of process validation.
Validation had proven to be an important tool for quality management of pharmaceutical according to ISO 9000:2000.
This document discusses drug metabolism, which involves the conversion of drugs from one chemical form to another through biotransformation reactions. It describes the two main phases of metabolism - Phase I and Phase II reactions. Phase I reactions involve oxidation, reduction, and hydrolysis and functionalize lipid-soluble drugs. Phase II reactions involve conjugating these functionalized drugs or their metabolites with endogenous compounds like glucuronic acid or sulfate, forming water-soluble drug conjugates that can be readily excreted. The key enzymes and reactions involved in each phase are discussed in detail.
A condition in which the heart is unable to pump sufficient blood to meet the metabolic demand of the body and also unable to receive it back because every time after a systole.
Hypertension is the most common cardiovascular disease determined by increase blood pressure (pressure exerted by blood against the wall of a blood vessel )in arteries.
The onset of hypertension is defined as having a blood pressure of 140/90 mm Hg or greater .
Hypertension is the major risk factor for coronary artery disease, heart failure, stroke and renal failure.
Anti-anginal agents are used to treat angina pectoris, which is characterized by chest pain due to insufficient oxygen supply to the heart. There are several classes of anti-anginal agents that work by different mechanisms: nitrates increase oxygen supply by dilating coronary arteries and reducing blood pressure; beta blockers decrease oxygen demand by lowering heart rate and blood pressure; calcium channel blockers increase oxygen supply and decrease demand by dilating arteries and relaxing smooth muscle. Organic nitrates are commonly used anti-anginal agents that work by dilating coronary arteries and veins to increase blood flow and decrease workload, thereby relieving chest pain.
In medicine, diuretics are used to treat heart failure, liver cirrhosis, hypertension, influenza, water poisoning, and certain kidney diseases.
different major types of diuretic drug
1. Carbonic Anhydrase Inhibitors2. Loop 3. Osmotic4. Potassium- sparing5. Thiazides
This document discusses antihyperlipidemic agents, which are drugs used to lower lipid levels in the blood. It focuses on statins, describing their mechanism of action as inhibiting HMG-CoA reductase to reduce cholesterol synthesis and increase LDL receptors. This decreases LDL and IDL and increases HDL levels. The document also classifies primary and secondary hyperlipidemias, describes other antihyperlipidemic drugs like ezetimibe, fibrates, and niacin, and recommends lifestyle changes and drug therapy to manage hyperlipidemia.
The document discusses various methods for separating the two enantiomers within a racemic mixture. The most common method is conversion of the racemic mixture to diastereomers using a chiral resolving agent, followed by fractional crystallization to separate the diastereomers based on differences in solubility. Other methods include differential absorption on a chiral chromatography column, enzymatic reactions that preferentially target one enantiomer, and kinetic resolution that exploits small differences in reaction rates between enantiomers. The goal of these resolution techniques is to produce pure samples of the individual enantiomers.
Hormones thyroid and antithyroidal agentsamol dighe
This document discusses thyroid hormones and antithyroid drugs. It begins by classifying hormones into different categories including thyroid hormones. It then describes the thyroid gland, its location and composition. The two principal thyroid hormones, thyroxine and triiodothyronine, are discussed along with their roles in metabolism and organ functioning. The biosynthesis and metabolism of thyroid hormones is explained involving thyroid stimulating hormones. Different classes of antithyroid drugs are then outlined, including thiomides, aniline derivatives, polyhydric phenols, and ionic inhibitors, describing their mechanisms of action in inhibiting thyroid hormone synthesis.
This document provides an overview of wound healing, its functions, stages, mechanisms, factors affecting it, and complications.
A wound is a break in the integrity of the skin or tissues, which may be associated with disruption of the structure and function.
Healing is the body’s response to injury in an attempt to restore normal structure and functions.
Healing can occur in two ways: Regeneration and Repair
There are 4 phases of wound healing: hemostasis, inflammation, proliferation, and remodeling. This document also describes the mechanism of wound healing. Factors that affect healing include infection, uncontrolled diabetes, poor nutrition, age, anemia, the presence of foreign bodies, etc.
Complications of wound healing like infection, hyperpigmentation of scar, contractures, and keloid formation.
This presentation includes basic of PCOS their pathology and treatment and also Ayurveda correlation of PCOS and Ayurvedic line of treatment mentioned in classics.
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.
How to Make a Field Mandatory in Odoo 17Celine George
In Odoo, making a field required can be done through both Python code and XML views. When you set the required attribute to True in Python code, it makes the field required across all views where it's used. Conversely, when you set the required attribute in XML views, it makes the field required only in the context of that particular view.
বাংলাদেশের অর্থনৈতিক সমীক্ষা ২০২৪ [Bangladesh Economic Review 2024 Bangla.pdf] কম্পিউটার , ট্যাব ও স্মার্ট ফোন ভার্সন সহ সম্পূর্ণ বাংলা ই-বুক বা pdf বই " সুচিপত্র ...বুকমার্ক মেনু 🔖 ও হাইপার লিংক মেনু 📝👆 যুক্ত ..
আমাদের সবার জন্য খুব খুব গুরুত্বপূর্ণ একটি বই ..বিসিএস, ব্যাংক, ইউনিভার্সিটি ভর্তি ও যে কোন প্রতিযোগিতা মূলক পরীক্ষার জন্য এর খুব ইম্পরট্যান্ট একটি বিষয় ...তাছাড়া বাংলাদেশের সাম্প্রতিক যে কোন ডাটা বা তথ্য এই বইতে পাবেন ...
তাই একজন নাগরিক হিসাবে এই তথ্য গুলো আপনার জানা প্রয়োজন ...।
বিসিএস ও ব্যাংক এর লিখিত পরীক্ষা ...+এছাড়া মাধ্যমিক ও উচ্চমাধ্যমিকের স্টুডেন্টদের জন্য অনেক কাজে আসবে ...
This slide is special for master students (MIBS & MIFB) in UUM. Also useful for readers who are interested in the topic of contemporary Islamic banking.
ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...PECB
Denis is a dynamic and results-driven Chief Information Officer (CIO) with a distinguished career spanning information systems analysis and technical project management. With a proven track record of spearheading the design and delivery of cutting-edge Information Management solutions, he has consistently elevated business operations, streamlined reporting functions, and maximized process efficiency.
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Date: May 29, 2024
Tags: Information Security, ISO/IEC 27001, ISO/IEC 42001, Artificial Intelligence, GDPR
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Training: ISO/IEC 27001 Information Security Management System - EN | PECB
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This presentation was provided by Steph Pollock of The American Psychological Association’s Journals Program, and Damita Snow, of The American Society of Civil Engineers (ASCE), for the initial session of NISO's 2024 Training Series "DEIA in the Scholarly Landscape." Session One: 'Setting Expectations: a DEIA Primer,' was held June 6, 2024.
Walmart Business+ and Spark Good for Nonprofits.pdfTechSoup
"Learn about all the ways Walmart supports nonprofit organizations.
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Special TechSoup offer for a free 180 days membership, and up to $150 in discounts on eligible orders.
Spark Good (walmart.com/sparkgood) is a charitable platform that enables nonprofits to receive donations directly from customers and associates.
Answers about how you can do more with Walmart!"
Main Java[All of the Base Concepts}.docxadhitya5119
This is part 1 of my Java Learning Journey. This Contains Custom methods, classes, constructors, packages, multithreading , try- catch block, finally block and more.
A workshop hosted by the South African Journal of Science aimed at postgraduate students and early career researchers with little or no experience in writing and publishing journal articles.
2. DEFINITION:
T h e ability of a chemical compound to a pharmacological/
therapeutic effect is related to the influence of various physical and
chemical (physicochemical) properties of the chemical substance on the
bio molecule that it interacts with.
1)Physical Properties
Physical property of drug is responsible for its action
2)Chemical Properties
The drug react extracellularly according to simple chemical
reactions like neutralization, chelation, oxidation etc.
4. 1. Solubility:
• The solubility of a substance at a given temperature is
defined as the concentration of the dissolved solute,
which is in equillibrium with the solid solute.
• Solubility depends on the nature of solute and solvent
as well as temperature , pH & pressure.
• The solubility of drug may be expressed in terms of its
affinity/philicity or repulsion/phobicity for either an
aqueous or organic solvent.
• The atoms and molecules of all organic substances
are held together by various types of bonds (e.g.
hydrogen bond, dipole –dipole, ionic bond etc.)
• These forces are involved in solubility because it is the
solvent- solvent, solute-solute, solvent-solute
interactions that governs solubility.
5. Methods to improve solubility of drugs
1)Structural modification (alter the structure of
molecules)
2)Use of Cosolvents (Ethanol, sorbitol,PPG,PEG)
3)Employing surfactants
4)Complexation
Importance of solubility
1.Solubility concept is important to pharmacist
because it govern the preparation of liquid dosage
form and the drug must be in solution before it is
absorbed by the body to produce the biological
activity.
6. 2. Partition Co-efficient
• Partition co-efficient is one of the Physicochemical
parameter which influencing the drug transport & drug
distribution., the way in which the drug reaches the site of
action from the site of application.
• Partition co-efficient is defined as equilibrium constant of
drugconcentration for unionized molecule in two phases.
P[Unionized molecule] = [drug]lipid
[drug]water
P[Ionized molecule] = [drug]lipid
[1-a ][drug]water
a=degree of ionization in aqueous solution
•Partition coefficient affects the drug transfer characteristics.
• Th e contribution of each functional group & structural
arrangement help to determine the lipophilic or hydrophilic
character of drug molecules.
7. Factors affecting Partition Co-efficient
pH
Co solvents
Surfactant
Complexation
• Partition Co-efficient are difficult to measure in living
system.
• They are usually determined in vitro 1-octanol as a
lipid phase and phosphate buffer of pH 7.4 as the
aqueous phase.
• 1-octanol as a lipid phase because,
•It has polar and nonpolar region
•Po/w is easy to measure
8. The Partition co-efficient, P is dimensionless and its logarithm, log
P is widely used as the measure of lipophilicity.
• The log P is measured by the following
methods.
1) Shake flask method
2) Chromatographic method (HPLC)
• Phenobarbitone has a high lipid/water partition
coefficient of 5.9. Thiopentone sodium has a
chloroform/water partition coefficient of about 100, so
it is highly soluble in lipid.
Hence, thiopentone sodium is used as ultra-short acting
barbiturates.
•
9. What else does lopP
affects?
log
P
Binding
to
enzymes
/receptor
Aqueous
solubility
Binding to
P450
metabolising
enzymes
Absorbance
through
membrane
Binging to
blood/tissue
proteins
10. Importance of partician coefficient• I t is generally used in combination with the Pka
to predict
the distribution of drug in biological system.
• The factor such as absorption, excretion &
penetration of theCNS may be related to the log P
value of drug.
• The drug should be designed with the lowest
possible
• L o g P, to reduce toxicity, nonspecific
binding& bioavailability.
11. 3. Hydrogen Bond
• The hydrogen bond is a special dipole-dipole
interaction between the hydrogen atom in a polar bond
such as N-H, O-H or F-H & electronegative atom O, N, F
atom.
• Dipoles result from unequal sharing of electrons
between atoms within a covalent bond.
• These are weak bonds and denoted as dotted lines. O-
H…….O, HN-H…….O,
• The compounds that are capable, of forming hydrogen
bonding is only soluble in water.
• hydrogen bonding is classified into 2 types:
• Intermolecular
• Intramolecular
12. 1) Intermolecular hydrogen bonding
• I t is occur between two or more than two molecules
of thesame or different compound.
• Due to this increase the boiling point of the
compound & increase the molecular weight of
compound hence more energy is required to
dissociate the molecular for vaporization.
13. 2) Intramolecular Hydrogen bonding
• H - bonding occurs within two atoms of the
samemolecules.
• This type of bonding is known as chelation and
frequently occurs in organic compounds.
• Sometimes h-bond develop six or five member rings
• Due to decrease the boilingpoint
salicylic
acid
o-
nitrophenol
O H
C
O
OH
O H
N
O
O
14. Hydrogen Bonding and biological action
N
NCH3
H3C
O
Eg. 1) Antipyrin i.e. 1- phenyl 2,3- dimethyl 5- pyrazolone has
analgesic activity.
C6H5
HN
H3 C
O
1-phenyl-3-methyl-5-pyrazolone is inactive.
C6 H5
HN
H
N
H3 C
O
15. Effect of H-bonding
All physical properties affected by H-
bonding,
1. Boiling and Melting point
2. Water solubility
3. Strength of acids
4. Spectroscopic properties
5. On surface tension and viscosity
6. Biological products
7. Drug-receptor interaction
16. 4. Chelation /Complexation
• Complex of drug molecules can’t cross the
natural membrane barriers, they render the drug
biological ineffectivity.
• The rate of absorption is proportional to the
concentration of thefree drug molecules i.e. the
diffusion of drug.
• Due to reversibility of the Complexation,
equillibrium between free drug and drug complex
•Drug + complexing agent Drug complex
• Complexation reduce the rate of absorption of drug
but not affect the availability of drug
17. Importance of chelates in medicine:
CHSH
1.Dimercaprol is a chelating agent.
CH2SH
+ As++
CH2S
CHS
CH2OH
As
a)Antidote for metal poisoning
CH3
H
C C COOH
SH NH2
CU++
CH2OH
2.Penicillamine
CH3
CH3 C
CH3
H
C COOH
S NH2
CU
1:1 chelate
CH3 C
CH3
S
H
C
NH2
COOH
UC
NH2 S
HOOC
CH3
CH3
1:2 chelate
18. • 8-Hydroxyquinoline and its analogs acts as antibacterial and
anti fungal agent by complexing with iron or copper.
•Undesirable side effects caused by drugs, which chelates with
metals.
• A side effect of Hydralazine a antihypertensive agent is
formation of anemia and this is due to chelation of the drug with
iron.
• Phenobarbital forms a non-absorbable
complex withpolyethylene glycol-4000.
• Calcium with EDTA form complex which is
increase thepermeability of membrane.
19. 5. Ionization of drug
• Most of the drugs are either weak acids or base and can
exist in either ionised or unionised state.
= Protonation or deprotonation
resulting in charged
Ionization
molecules.
The ionization of the drug depends on its pKa
& pH.• The rate of drug absorption is directly proportional to the
concentration of the drug at absorbable form but not the
concentration of the drug at the absorption site.
• Ionization form imparts good water solubility to the drug
which is required of binding of drug and receptor
interaction
•Unionized form helps the drug to cross the cell
membrane.
•Eg; Barbituric acid is inactive because it is strong
20. According to Henderson-Hasselbalch
equation pH-pKa = log
[ionized/unionised] pH-pKa
= log
[unionized/ionised]
for
acids
for
base
%
ionisation
= 100[ 1+10 (pH-
pka)]
When an acid or base is 50% ionised: pH = pKa
Eg: the solution of weak acid Aspirin in stomach (pH-1.0) will get
readily absorbed because it is in the un-ionosed form(99%).
H A H 2 O H 3 O +
C o n j u g a t e
a c i d
A -
C o n u g a t e
A c i d
B H + H 2 O H 3 O +
B
C o n u g a t e
b a s e
U n i o n i z e d
A c i d
i o n i s e d C o n u g a t e
a c i d
21. Eg:Phenytoin injection must be adjusted to pH12 with Sodium
Hydroxide to obtain 99.98% of the drug in ionised form.
Tropicamide eye drops an anti cholinergic drug has a pkaof 5.2
and the drug has to be buffered to pH 4 to obtain more than 90%
ionisation.
Importance of Ionization of drug
Weak acid at acid pH: more lipid soluble because it isuncharged,
the uncharged form more readily passes through the biological
membranes.
RCOO- + H+ = RCOOH
Weak base at alkaline pH: more lipid soluble because it is
uncharged, the uncharged form more readily passes through
the biological membranes.
RNH+ = RNH2+ H+
22. 6. Redox Potential
• The oxidation-reduction potential may be defined
as a quantitative expression of the tendency that a
compound has to give or receive electrons.
• The correlation between redox potential and
biological activity can only be drawn for the
compound of very similar structure and properties.
• The redox potential of a system may be
calculated fromthefollowing equation.
• E=E0+0.0592/n log[conc. of reductant /conc. of oxidant]
23. Examples,
1) Riboflavin analogues
The biological activity of riboflavin is due to E =-
0.185volt
.
N
NH
O
N
OH
OH
OH
OH
N O
riboflavin
0Riboflavin E = -0.185 V
Riboflavin analogue E0 = -0.095V
N
N H
N
O H
O H
O H
O H
N O
O
Dichloro riboflavin
C l
C l
2).The optimum bacteriostatic activity in quinones is
associated
with the redox potentialat +0.03 volt, when tested
24. 7. Surface Activity
• Surfactant is defined as a material that can reduce the surface tension
of water at very low concentration.
• Surface active agents affect the drug absorption which depends on:
•1The chemical nature of surfactant
•2.Its concentration
•3.Its affect on biological membrane and the micelle formation.
• In lower conc. of surfactant enhanced the rate of absorption because
amphiphilies reduces the surface tension and better absorption.
• In higher conc. of surfactant reduced the rate of absorption.
Applications:
1.The antihelmentic activity of hexylresorcinol
2.Bactericidal activity of cationic quaternary ammonium
compounds. 3.Bactericidal activity of aliphatic alcohols.
4.Disinfectant action of phenol and cresol.
5. Bile salt solutions of approximately physiological concentration
greatly enhance the dissolution rate of poorly water soluble drugs
like grasiofulvin, hexestrol by micellar solubilization effect.
25. 8. Protein binding
• The reversible binding of protein with non-specific and non-
functional site on the body protein without showing any
biological effect is called as protein binding.
•Protein + drug ⇌Protein-drug complex
• Dependingon the whether the drug is a weak or strong acid,base
or is neutral, it can bind to single blood proteins to multiple
proteins (sereum albumin, acid-gycoprotien or lipoproteins).The
most significant protein involved in the binding of drug is albumin,
which comprises more than half of blood proteins.
26. • Stereochemistry involve the study of three
dimensional nature of molecules. It is study of the
chiral molecules.
• Stereochemistry plays a major role in the
pharmacological properties because;
• Any change in stereo specificity of the drug will affect
its pharmacological activity
• The isomeric pairs have different physical properties (log
p, pKa etc.) and thus differ in pharmacological activity.
• The isomer which have same bond connectivity but
different arrangement of groups or atoms in the space are
termed stereoisomer.
9. Stereochemistry of drugs
27. Conformational Isomers
• Different arrangement of atoms that can be converted into
one another by rotation about single bonds are called
conformations.
• Rotation about bonds allows inter conversion of
conformers.
28. Optical Isomers
• Stereochemistry, enantiomers, symmetry andchirality are
impotant concept in therapeutic and toxic effect of drug.
• A chiral compound containing one asymmetric centre
has two enantiomers. Although each enantiomer has
identical chemical & physical properties, they may have
different physiological activity like interaction with
receptor, metabolism & protein binding.
• A optical isomers in biological action is due to one
isomer being able to achieve a three point attachment with
its receptor molecule while its enantiomer would only be
able to achieve a two point attachment with the same
molecule.
29. E.g. Ephedrine &
Psuedoephedrin
e
MP = 37-39
1 gram/20 mL
MP = 118-120
1 gram/200 mL
Ephedrine
(Erythro)
CH3
NHCH3
OH
H
H
Pseudoephedrine
(Threo)
CH3
NHCH3
H
H
HO
30. • The category of drugs where the two isomers have
qualitatively similar pharmacological activity but have
different quantitative potencies.
O
O
OH
O
(s)-(-)warfarin
O
OH
O O
(R)-(+)warfarin
31. • Geometric Isomerism
Geometric isomerism is represented by cis/trans
isomerism resulting from restricted rotation due to
carbon-carbon double bond or in rigid ring system.
OH
HO OH
HO
trans-diethylstibesterol
Estrogenic activity
cis-diethylstibesterol
Only 7% activity
of the trans isomer
32. • Longmuir introduced the term isosterism in 1919, which
postulated that two molecules or molecular fragments
containing an identical number and arrangament of electron
should have similar properties and termed as isosteres.
• Isosteres should be isoelectric i.e. they should
possess same total charge.
• Bioisosterism is defined as compounds or groups that
possess near or equal molecular shapes and volumes,
approximately the same distribution of electron and which
exhibit similar physical properties.
• They are classified into two
types., i)Classical biososteres
ii)Non classical bioisosters.
33. Classical Bioisosteres
• They have similarities of shape and electronic configuration of
atoms, groups and molecules which they replace.
The classical bioisosteres
may be,
Univalent atoms and groups
i) Cl, Br, I ii) CH3, NH2, -OH,
-SH
Bivalent atoms and groups
i) R-O-R,R-NH-R, R-S-R,
RCH2R
ii) –CONHR, -COOR, -
COSR
34. Application of Classical Bioisosteres in in drug design
i) Replacement of –NH 2 group by –
CH3 group.
Carbutami
de
Tolbutamid
e
R=
NH2
R=
CH3
ii)Replacement of –OH &
-SH
X
Guanine= -OH
6-Thioguanine = -
SH
R SO2 NH CONH(CH2)3CH3
N H
N
N
H 2 N
H N
35. Non - classical Bioisosteres
• They do not obey the stearic and electronic definition of classical
isosteres.
• Non-classical biosteres are functional groups with dissimilar valence
electron configuration.
• Specific characteristics:
• Electronic properties
• Physicochemical property of molecule
• Spatical arrangement
• Functional moiety for biological activity
36. A classical e.g.of ringVs. noncycclic structure is Diethylstilbosterol & 17-ß
oestradiol.
OH
H
H H
HO
17-ß
oestradiol.
OH
HO
trans-diethylstibesterol