This document discusses factors that affect drug absorption from various dosage forms. It covers pharmaceutical factors like drug properties, formulation variables, and dosage form type. It also discusses patient factors like age, gastric emptying time, and disease states. The key points are that drug solubility, dissolution rate, particle size, and polymorphism impact absorption. Immediate release solutions and suspensions have the fastest absorption while controlled release formulations are slower. Other factors like pH, lipophilicity, and dosage form properties also influence a drug's absorption in the body.
This document discusses drug excretion and methods to prolong drug action. It defines excretion as the process of removing drugs from the body and terminating their action. The major routes of excretion are renal (urinary), biliary, pulmonary, intestinal and through sweat glands. Renal excretion occurs through glomerular filtration, tubular secretion and reabsorption. Factors that influence renal excretion include physicochemical drug properties, plasma concentration, distribution/binding, renal blood flow, disease states, and drug interactions. Non-renal routes and methods to prolong drug action through enterohepatic recycling are also examined.
The document discusses nonlinear pharmacokinetics and chronopharmacokinetics. Nonlinear pharmacokinetics occurs when the body's absorption, distribution, metabolism, or excretion of a drug becomes saturated at higher doses. This can cause the rate of drug elimination to decrease. Examples of processes that can become saturated include drug metabolism and renal excretion. Circadian rhythms can also impact drug pharmacokinetics by influencing absorption, distribution, metabolism, and excretion over 24-hour periods. Accounting for these temporal changes can improve drug therapy for circadian phase-dependent diseases.
Pharmacokinetics / Biopharmaceutics - IntroductionAreej Abu Hanieh
This document provides an introduction to pharmacokinetics, biopharmaceutics, pharmacodynamics, clinical pharmacokinetics, and toxicokinetics. It discusses how pharmacokinetics describes the absorption, distribution, metabolism and excretion of drugs in the body. Biopharmaceutics examines how the physical properties of drugs and dosage forms influence drug absorption. Pharmacodynamics studies the biochemical and physiological effects of drugs. Clinical pharmacokinetics applies these principles to optimize drug therapy for patients. Toxicokinetics and clinical toxicology evaluate adverse drug effects.
Seminar on pharmacokinetic parameters of two compartment open modelDivya Singh
This document discusses the two compartment open pharmacokinetic model. It describes the central and peripheral compartments and the first-order rate constants between them. It provides equations to model drug concentration over time for intravenous bolus, intravenous infusion, and extravascular administration. Parameters like volume of distribution, clearance, and half-life can be derived from the model.
The document discusses three main theories of drug dissolution:
1) Diffusion layer/film theory which describes dissolution as a two step process of drug dissolving from the solid to form a saturated film and then diffusing out of the film. The rate of dissolution is given by the Noyes-Whitney equation.
2) Danckwert's/surface renewal theory which accounts for eddies in the solution exposing new surface areas for dissolution. The rate is expressed as the product of the surface renewal rate and concentration gradient.
3) Interfacial barrier model which assumes the reaction at the solid surface is slower than diffusion, making interfacial transport the rate limiting step described by another equation.
Methods of enhancing Dissolution and bioavailability of poorly soluble drugsRam Kanth
Bioavailability refers to the amount of drug that reaches systemic circulation after administration. It is reduced when drugs are administered orally rather than intravenously due to incomplete absorption and first-pass metabolism. The document discusses several methods for enhancing bioavailability of orally administered drugs with poor solubility or permeability. These include micronization, use of surfactants, salt forms, altering pH, polymorphism, complexation, molecular encapsulation, and forming solid solutions, eutectic mixtures or solid dispersions to improve solubility and dissolution rate.
1. Drug absorption involves the movement of unchanged drug molecules from the site of administration into systemic circulation. It occurs primarily through the gastrointestinal (GI) tract and is influenced by factors like solubility, permeability, and transport mechanisms.
2. There are three main mechanisms of drug transport across the GI tract - transcellular, paracellular, and vesicular. Transcellular transport occurs across cells and includes passive diffusion, active transport, and carrier-mediated transport. Paracellular transport is between cell junctions. Vesicular transport involves endocytosis within cells.
3. The most common mechanism is passive diffusion, which does not require energy. Other mechanisms like active transport and carrier-mediated transport use
This document discusses drug excretion and methods to prolong drug action. It defines excretion as the process of removing drugs from the body and terminating their action. The major routes of excretion are renal (urinary), biliary, pulmonary, intestinal and through sweat glands. Renal excretion occurs through glomerular filtration, tubular secretion and reabsorption. Factors that influence renal excretion include physicochemical drug properties, plasma concentration, distribution/binding, renal blood flow, disease states, and drug interactions. Non-renal routes and methods to prolong drug action through enterohepatic recycling are also examined.
The document discusses nonlinear pharmacokinetics and chronopharmacokinetics. Nonlinear pharmacokinetics occurs when the body's absorption, distribution, metabolism, or excretion of a drug becomes saturated at higher doses. This can cause the rate of drug elimination to decrease. Examples of processes that can become saturated include drug metabolism and renal excretion. Circadian rhythms can also impact drug pharmacokinetics by influencing absorption, distribution, metabolism, and excretion over 24-hour periods. Accounting for these temporal changes can improve drug therapy for circadian phase-dependent diseases.
Pharmacokinetics / Biopharmaceutics - IntroductionAreej Abu Hanieh
This document provides an introduction to pharmacokinetics, biopharmaceutics, pharmacodynamics, clinical pharmacokinetics, and toxicokinetics. It discusses how pharmacokinetics describes the absorption, distribution, metabolism and excretion of drugs in the body. Biopharmaceutics examines how the physical properties of drugs and dosage forms influence drug absorption. Pharmacodynamics studies the biochemical and physiological effects of drugs. Clinical pharmacokinetics applies these principles to optimize drug therapy for patients. Toxicokinetics and clinical toxicology evaluate adverse drug effects.
Seminar on pharmacokinetic parameters of two compartment open modelDivya Singh
This document discusses the two compartment open pharmacokinetic model. It describes the central and peripheral compartments and the first-order rate constants between them. It provides equations to model drug concentration over time for intravenous bolus, intravenous infusion, and extravascular administration. Parameters like volume of distribution, clearance, and half-life can be derived from the model.
The document discusses three main theories of drug dissolution:
1) Diffusion layer/film theory which describes dissolution as a two step process of drug dissolving from the solid to form a saturated film and then diffusing out of the film. The rate of dissolution is given by the Noyes-Whitney equation.
2) Danckwert's/surface renewal theory which accounts for eddies in the solution exposing new surface areas for dissolution. The rate is expressed as the product of the surface renewal rate and concentration gradient.
3) Interfacial barrier model which assumes the reaction at the solid surface is slower than diffusion, making interfacial transport the rate limiting step described by another equation.
Methods of enhancing Dissolution and bioavailability of poorly soluble drugsRam Kanth
Bioavailability refers to the amount of drug that reaches systemic circulation after administration. It is reduced when drugs are administered orally rather than intravenously due to incomplete absorption and first-pass metabolism. The document discusses several methods for enhancing bioavailability of orally administered drugs with poor solubility or permeability. These include micronization, use of surfactants, salt forms, altering pH, polymorphism, complexation, molecular encapsulation, and forming solid solutions, eutectic mixtures or solid dispersions to improve solubility and dissolution rate.
1. Drug absorption involves the movement of unchanged drug molecules from the site of administration into systemic circulation. It occurs primarily through the gastrointestinal (GI) tract and is influenced by factors like solubility, permeability, and transport mechanisms.
2. There are three main mechanisms of drug transport across the GI tract - transcellular, paracellular, and vesicular. Transcellular transport occurs across cells and includes passive diffusion, active transport, and carrier-mediated transport. Paracellular transport is between cell junctions. Vesicular transport involves endocytosis within cells.
3. The most common mechanism is passive diffusion, which does not require energy. Other mechanisms like active transport and carrier-mediated transport use
This document provides an overview of aerosols for pharmaceutical use. It begins with introductions to aerosols and pharmaceutical aerosols. The main components of aerosols are then described, including propellants, containers, valves, and actuators. Various aerosol systems like solution, suspension, and foam systems are also outlined. The document concludes with sections on the formulation, manufacturing, and quality control of pharmaceutical aerosols.
This document provides information about the nutraceutical properties of various herbs and foods. It discusses the health benefits of nutraceuticals in treating diseases like diabetes, cardiovascular diseases, cancer, and gastrointestinal issues. Key points covered include the classification of nutraceuticals, probiotics and prebiotics, polyunsaturated fatty acids, vitamins, and the traditional and global market of nutraceuticals. Specific herbs discussed include alfalfa, chicory, ginger, fenugreek, garlic, and honey.
Physicochemical Properties effect on Absorption of DrugsSuraj Choudhary
This document discusses factors affecting drug absorption from oral dosage forms. It covers physiological factors like gastric emptying time and pH, as well as physicochemical drug properties including solubility, dissolution rate, and polymorphism that influence drug absorption. Particle size and surface area are emphasized, with smaller particles increasing absorption for hydrophilic drugs but potentially decreasing it for hydrophobic drugs. The pH partition hypothesis and importance of drug stability are also summarized.
The document discusses compartment modeling and one compartment open models. It describes how the body can be represented as a single well-mixed compartment and outlines the assumptions of compartmental models. It then covers one compartment open models for intravenous bolus administration, intravenous infusion, and extravascular administration. For intravenous bolus administration, the elimination phase can be characterized by parameters like elimination rate constant, half-life, and clearance. Intravenous infusion allows for constant rate input into the compartment. Extravascular administration models absorption as either zero-order or first-order kinetics.
This document describes the two compartment open model for drug distribution and elimination. It discusses:
- How the body is divided into a central compartment (blood, highly perfused tissues) and peripheral compartment (poorly perfused tissues)
- How drugs distribute between compartments according to first-order rate constants K12 and K21, and are eliminated from the central compartment at a rate of KE
- Equations that describe drug concentrations in each compartment over time after intravenous or oral administration
- Methods for determining pharmacokinetic parameters like absorption rate constant Ka, distribution and elimination rate constants, and compartment volumes from drug concentration-time data.
Bio pharmaceutical classification System [BCS]Sagar Savale
The Biopharmaceutical Classification System was first developed by in 1995, by Amidon et al & his colleagues.
Definition:
“The Biopharmaceutical Classification System is a scientific framework for classifying a drug substance based on its aqueous solubility & intestinal permeability & dissolution rate”.
To saved time fast screening is required so drug substances are classified on basis of solubility and permeability. This classification is called Biopharmaceutical Classification System
This document discusses in vitro-in vivo correlations (IVIVCs). It defines IVIVC as a predictive mathematical model relating an in vitro property (e.g. dissolution rate) to an in vivo response (e.g. absorption rate). The document outlines the significance of IVIVCs in reducing bioequivalence studies and supporting biowaivers. It describes different levels of IVIVC (A, B, C) and parameters that can be correlated (dissolution rate to absorption rate; percent dissolved to percent absorbed). The document provides examples of IVIVC case studies and concludes that current regulatory guidelines only apply to oral dosage forms, while further research is needed to develop IVIVCs for other drug products.
The document discusses the pH partition theory of drug absorption from the gastrointestinal tract. The theory states that a drug's absorption is governed by its dissociation constant (pKa), the lipid solubility of its unionized form, and the pH of the absorption site. According to the theory, only the unionized form of an acid or base drug can be absorbed if it is sufficiently lipid soluble. The fraction of a drug in its unionized form depends on the drug's pKa and the pH of the solution based on the Henderson-Hasselbalch equation. While the pH partition theory explains many observations, it has limitations such as not accounting for the presence of an unstirred water layer and virtual membrane pH at the absorption
The document discusses invitro dissolution testing. It begins with an introduction to dissolution and BCS classification. It then covers theories of dissolution like the diffusion layer model. It describes various invitro dissolution test models including non-sink methods like the USP rotating basket and paddle apparatus and sink methods like the flow through column method. Finally, it discusses factors that can affect dissolution testing and provides a conclusion.
This document discusses factors that influence the absorption of drugs in the gastrointestinal tract. It outlines various physicochemical and dosage form factors that can impact a drug's solubility, dissolution rate, and absorption. The key physicochemical factors discussed are drug solubility, particle size, polymorphism, salt form, and lipophilicity. Theories of drug dissolution like the diffusion layer model and Danckwert's model are also summarized. The principle of bioequivalence studies and factors like disease state, gastrointestinal contents, and presystemic metabolism that can influence drug absorption are briefly covered as well.
Absorption of drugs from non per os extravascular administrationSuvarta Maru
Non-oral routes of drug administration provide advantages over oral routes by bypassing the gastrointestinal tract and avoiding first-pass metabolism. Common non-oral routes discussed include buccal/sublingual, rectal, topical, intramuscular, subcutaneous, pulmonary, intranasal, intraocular, and vaginal administration. Absorption through these routes occurs primarily via passive diffusion, carrier-mediated transport, or pore transport depending on the drug properties and administration site. Non-oral routes allow for rapid drug absorption, higher bioavailability compared to oral routes, and targeted delivery for local or systemic effects.
This document discusses pellets, which are small spherical units used to deliver drugs. It covers pellet formulation requirements, manufacturing processes like extrusion-spheronization, and characterization methods. Pellets offer benefits like uniform dosing and controlled release. They are made by agglomerating powders using water or other liquids to form nuclei that grow in size. Key processes include granulation, extrusion, spheronization, and coating layers onto seeds or cores. Pellets are characterized based on size, shape, porosity, and dissolution profile. Controlling these properties allows pellets to improve drug delivery.
The document discusses the Biopharmaceutics Classification System (BCS), which is a framework developed by the FDA to classify drugs based on their aqueous solubility and intestinal permeability. The BCS aims to improve drug development and review processes by identifying when clinical bioequivalence tests are not necessary. It classifies drugs as Class I (high solubility, high permeability), Class II (low solubility, high permeability), Class III (high solubility, low permeability) or Class IV (low solubility, low permeability) based on their solubility and permeability parameters. The classification can help determine if in vitro dissolution tests alone can demonstrate bioequivalence or if in vivo testing is still required.
This document discusses renal and non-renal routes of drug excretion. It describes the key organs and processes involved in excretion, including the nephron in renal excretion and factors that determine if a drug is excreted renally or non-renally. Non-renal excretion includes biliary excretion through the liver and bile ducts. Clearance, excretion ratio, and other pharmacokinetic concepts relating to measurement of excretion are also covered.
The document discusses chemotherapy and anticancer drugs. It defines malignancy as cancer, describes cancer cell characteristics and the cell cycle. It then classifies and lists various antineoplastic/anticancer drugs including alkylating agents, antimetabolites, natural products, miscellaneous drugs, hormones and antagonists. The document also lists common cancer types, anticancer drugs available as injections, tablets and capsules. It briefly discusses uses of radioactive isotopes and how response to chemotherapy is judged. The goal of treatment is improving patient's quality of life.
This document discusses hard and soft gelatin capsules. It defines capsules as solid dosage forms where the drug substance is enclosed within soluble gelatin shells. Hard gelatin capsules consist of two pieces (cap and body) while soft gelatin capsules have a single flexible shell. The document describes the production process for hard capsules including dipping, drying, and filling steps. It also discusses advantages like taste masking and disadvantages like incompatibility with hygroscopic drugs. Quality control tests for capsules include disintegration, weight variation, and dissolution testing.
The document discusses parenteral products and their administration. It defines parenteral as referring to administration by injection rather than orally, bypassing the gastrointestinal tract. It then discusses the advantages and disadvantages of the parenteral route, including faster systemic delivery but also risks of infection. The document outlines various routes of parenteral injection and provides details on procedures like subcutaneous, intramuscular, and intravenous injection. It also discusses formulation, processing, and quality testing of parenteral products.
A drug injected intravascularly directly enters the systemic circulation and exerts its pharmacological effects.
Majority of drugs administered extravascularly, generally orally.
If intended to act systemically, such drugs can exert their pharmacological actions only when they come into blood circulation from their site of application. So, absorption is an important step.
The document discusses factors that affect drug absorption after administration. It describes how pharmaceutical factors like drug properties, formulation characteristics, and excipients can impact a drug's dissolution rate and permeability through membranes, thus influencing absorption. Patient factors are also discussed, such as gastrointestinal pH, transit time, and metabolic enzymes, which determine how much of a drug ultimately reaches the systemic circulation. The key factors discussed are drug solubility, particle size, polymorphism, salt form, and lipophilicity as they relate to a drug's absorption based on the pH-partition hypothesis.
This document provides an overview of aerosols for pharmaceutical use. It begins with introductions to aerosols and pharmaceutical aerosols. The main components of aerosols are then described, including propellants, containers, valves, and actuators. Various aerosol systems like solution, suspension, and foam systems are also outlined. The document concludes with sections on the formulation, manufacturing, and quality control of pharmaceutical aerosols.
This document provides information about the nutraceutical properties of various herbs and foods. It discusses the health benefits of nutraceuticals in treating diseases like diabetes, cardiovascular diseases, cancer, and gastrointestinal issues. Key points covered include the classification of nutraceuticals, probiotics and prebiotics, polyunsaturated fatty acids, vitamins, and the traditional and global market of nutraceuticals. Specific herbs discussed include alfalfa, chicory, ginger, fenugreek, garlic, and honey.
Physicochemical Properties effect on Absorption of DrugsSuraj Choudhary
This document discusses factors affecting drug absorption from oral dosage forms. It covers physiological factors like gastric emptying time and pH, as well as physicochemical drug properties including solubility, dissolution rate, and polymorphism that influence drug absorption. Particle size and surface area are emphasized, with smaller particles increasing absorption for hydrophilic drugs but potentially decreasing it for hydrophobic drugs. The pH partition hypothesis and importance of drug stability are also summarized.
The document discusses compartment modeling and one compartment open models. It describes how the body can be represented as a single well-mixed compartment and outlines the assumptions of compartmental models. It then covers one compartment open models for intravenous bolus administration, intravenous infusion, and extravascular administration. For intravenous bolus administration, the elimination phase can be characterized by parameters like elimination rate constant, half-life, and clearance. Intravenous infusion allows for constant rate input into the compartment. Extravascular administration models absorption as either zero-order or first-order kinetics.
This document describes the two compartment open model for drug distribution and elimination. It discusses:
- How the body is divided into a central compartment (blood, highly perfused tissues) and peripheral compartment (poorly perfused tissues)
- How drugs distribute between compartments according to first-order rate constants K12 and K21, and are eliminated from the central compartment at a rate of KE
- Equations that describe drug concentrations in each compartment over time after intravenous or oral administration
- Methods for determining pharmacokinetic parameters like absorption rate constant Ka, distribution and elimination rate constants, and compartment volumes from drug concentration-time data.
Bio pharmaceutical classification System [BCS]Sagar Savale
The Biopharmaceutical Classification System was first developed by in 1995, by Amidon et al & his colleagues.
Definition:
“The Biopharmaceutical Classification System is a scientific framework for classifying a drug substance based on its aqueous solubility & intestinal permeability & dissolution rate”.
To saved time fast screening is required so drug substances are classified on basis of solubility and permeability. This classification is called Biopharmaceutical Classification System
This document discusses in vitro-in vivo correlations (IVIVCs). It defines IVIVC as a predictive mathematical model relating an in vitro property (e.g. dissolution rate) to an in vivo response (e.g. absorption rate). The document outlines the significance of IVIVCs in reducing bioequivalence studies and supporting biowaivers. It describes different levels of IVIVC (A, B, C) and parameters that can be correlated (dissolution rate to absorption rate; percent dissolved to percent absorbed). The document provides examples of IVIVC case studies and concludes that current regulatory guidelines only apply to oral dosage forms, while further research is needed to develop IVIVCs for other drug products.
The document discusses the pH partition theory of drug absorption from the gastrointestinal tract. The theory states that a drug's absorption is governed by its dissociation constant (pKa), the lipid solubility of its unionized form, and the pH of the absorption site. According to the theory, only the unionized form of an acid or base drug can be absorbed if it is sufficiently lipid soluble. The fraction of a drug in its unionized form depends on the drug's pKa and the pH of the solution based on the Henderson-Hasselbalch equation. While the pH partition theory explains many observations, it has limitations such as not accounting for the presence of an unstirred water layer and virtual membrane pH at the absorption
The document discusses invitro dissolution testing. It begins with an introduction to dissolution and BCS classification. It then covers theories of dissolution like the diffusion layer model. It describes various invitro dissolution test models including non-sink methods like the USP rotating basket and paddle apparatus and sink methods like the flow through column method. Finally, it discusses factors that can affect dissolution testing and provides a conclusion.
This document discusses factors that influence the absorption of drugs in the gastrointestinal tract. It outlines various physicochemical and dosage form factors that can impact a drug's solubility, dissolution rate, and absorption. The key physicochemical factors discussed are drug solubility, particle size, polymorphism, salt form, and lipophilicity. Theories of drug dissolution like the diffusion layer model and Danckwert's model are also summarized. The principle of bioequivalence studies and factors like disease state, gastrointestinal contents, and presystemic metabolism that can influence drug absorption are briefly covered as well.
Absorption of drugs from non per os extravascular administrationSuvarta Maru
Non-oral routes of drug administration provide advantages over oral routes by bypassing the gastrointestinal tract and avoiding first-pass metabolism. Common non-oral routes discussed include buccal/sublingual, rectal, topical, intramuscular, subcutaneous, pulmonary, intranasal, intraocular, and vaginal administration. Absorption through these routes occurs primarily via passive diffusion, carrier-mediated transport, or pore transport depending on the drug properties and administration site. Non-oral routes allow for rapid drug absorption, higher bioavailability compared to oral routes, and targeted delivery for local or systemic effects.
This document discusses pellets, which are small spherical units used to deliver drugs. It covers pellet formulation requirements, manufacturing processes like extrusion-spheronization, and characterization methods. Pellets offer benefits like uniform dosing and controlled release. They are made by agglomerating powders using water or other liquids to form nuclei that grow in size. Key processes include granulation, extrusion, spheronization, and coating layers onto seeds or cores. Pellets are characterized based on size, shape, porosity, and dissolution profile. Controlling these properties allows pellets to improve drug delivery.
The document discusses the Biopharmaceutics Classification System (BCS), which is a framework developed by the FDA to classify drugs based on their aqueous solubility and intestinal permeability. The BCS aims to improve drug development and review processes by identifying when clinical bioequivalence tests are not necessary. It classifies drugs as Class I (high solubility, high permeability), Class II (low solubility, high permeability), Class III (high solubility, low permeability) or Class IV (low solubility, low permeability) based on their solubility and permeability parameters. The classification can help determine if in vitro dissolution tests alone can demonstrate bioequivalence or if in vivo testing is still required.
This document discusses renal and non-renal routes of drug excretion. It describes the key organs and processes involved in excretion, including the nephron in renal excretion and factors that determine if a drug is excreted renally or non-renally. Non-renal excretion includes biliary excretion through the liver and bile ducts. Clearance, excretion ratio, and other pharmacokinetic concepts relating to measurement of excretion are also covered.
The document discusses chemotherapy and anticancer drugs. It defines malignancy as cancer, describes cancer cell characteristics and the cell cycle. It then classifies and lists various antineoplastic/anticancer drugs including alkylating agents, antimetabolites, natural products, miscellaneous drugs, hormones and antagonists. The document also lists common cancer types, anticancer drugs available as injections, tablets and capsules. It briefly discusses uses of radioactive isotopes and how response to chemotherapy is judged. The goal of treatment is improving patient's quality of life.
This document discusses hard and soft gelatin capsules. It defines capsules as solid dosage forms where the drug substance is enclosed within soluble gelatin shells. Hard gelatin capsules consist of two pieces (cap and body) while soft gelatin capsules have a single flexible shell. The document describes the production process for hard capsules including dipping, drying, and filling steps. It also discusses advantages like taste masking and disadvantages like incompatibility with hygroscopic drugs. Quality control tests for capsules include disintegration, weight variation, and dissolution testing.
The document discusses parenteral products and their administration. It defines parenteral as referring to administration by injection rather than orally, bypassing the gastrointestinal tract. It then discusses the advantages and disadvantages of the parenteral route, including faster systemic delivery but also risks of infection. The document outlines various routes of parenteral injection and provides details on procedures like subcutaneous, intramuscular, and intravenous injection. It also discusses formulation, processing, and quality testing of parenteral products.
A drug injected intravascularly directly enters the systemic circulation and exerts its pharmacological effects.
Majority of drugs administered extravascularly, generally orally.
If intended to act systemically, such drugs can exert their pharmacological actions only when they come into blood circulation from their site of application. So, absorption is an important step.
The document discusses factors that affect drug absorption after administration. It describes how pharmaceutical factors like drug properties, formulation characteristics, and excipients can impact a drug's dissolution rate and permeability through membranes, thus influencing absorption. Patient factors are also discussed, such as gastrointestinal pH, transit time, and metabolic enzymes, which determine how much of a drug ultimately reaches the systemic circulation. The key factors discussed are drug solubility, particle size, polymorphism, salt form, and lipophilicity as they relate to a drug's absorption based on the pH-partition hypothesis.
Factors affecting Drug Absorption Part II.pptxRani Dhole
The document discusses several biopharmaceutical factors that influence drug absorption from the gastrointestinal tract, including physicochemical properties of the drug, dosage form characteristics, and patient factors. Specifically, it covers how a drug's solubility, particle size, polymorphic form, salt form, acid-base properties (pKa), and lipophilicity can impact dissolution and absorption. It also describes limitations of the pH-partition hypothesis for predicting drug absorption. In summary, a drug's biopharmaceutical properties and dosage form design can either enhance or impede gastrointestinal drug absorption.
This document discusses factors that influence drug absorption, including pharmaceutical and patient-related factors. Pharmaceutical factors include physicochemical properties of the drug like solubility, particle size, and polymorphism/amorphism. They also include formulation properties such as disintegration time, dosage form, and ingredients. Patient factors include physiological variables. Together these factors determine how well a drug is absorbed after administration and reaches systemic circulation.
Factor influencing bioavailability and bioequivalence can be divided into pharmaceutical and patient related factors. Pharmaceutical factors include chemical properties like solubility, particle size and polymorphism which impact dissolution rate and absorption. Formulation properties such as disintegration time, dosage form type and storage conditions also influence bioavailability. Patient related factors involve physiological variations in gastric emptying, intestinal pH and transit time as well as disease states which can all impact drug absorption. Together, consideration of these influencing parameters is important for understanding and assessing bioavailability and bioequivalence.
Factor influencing bioavailability and bioequivalence can be divided into pharmaceutical and patient related factors. Pharmaceutical factors include chemical properties like solubility, particle size and polymorphism which impact dissolution rate and absorption. Formulation properties like disintegration time, dosage form type and storage conditions also influence bioavailability. Patient related factors involve physiological variations in gastric emptying, intestinal pH and transit time as well as disease states which can all impact drug absorption. Together, these pharmaceutical and biological factors determine the fraction of drug that reaches systemic circulation.
This document discusses biopharmaceutical factors that can affect the bioavailability of drugs. It focuses on pharmaceutical factors including physicochemical properties of drug molecules and dosage form characteristics. Physicochemical properties like solubility, dissolution rate, particle size, polymorphism, salt form, and ionization state can impact drug absorption. The pH-partition hypothesis explains how a drug's pKa and lipid solubility relate to absorption based on gastrointestinal pH. Dosage form properties such as disintegration time, manufacturing methods, and ingredients are also discussed as formulation factors influencing bioavailability.
Drug absorption refers to the movement of an unchanged drug from the site of administration into systemic circulation. It is affected by pharmaceutical, formulation, physiological, and patient-related factors. Pharmaceutical factors include a drug's solubility, particle size, polymorphism, salt form, and ionization state which impact dissolution rate and permeability. Formulation factors like disintegration time, excipients, and dosage form properties also influence absorption. Physiological factors such as gastrointestinal motility, pH, enzyme activity, blood flow, and food intake can impact drug stability and transit time in the GI tract. Patient characteristics such as age, disease state, and genetics additionally determine absorption. Together, these multifaceted factors determine the degree and rate of drug
Presentation fACTOR AFFECTING DRUGSABSORPTION by deepak kumarDrx Kumar
This seminar discusses factors affecting drug absorption from oral dosage forms. It outlines pharmaceutical factors such as chemical properties, physicochemical properties, formulation factors, and patient-related physiological factors. Pharmaceutical factors include drug solubility, particle size, polymorphism, dosage form, and excipients. Patient factors include membrane transport mechanisms, gastrointestinal motility, food effects, age, and disease states. Together, these factors determine the rate and extent of drug absorption from oral dosage forms.
Biopharmaceutics is the study of physicochemical properties of drugs and how they influence the drug's bioavailability. Key factors that can impact bioavailability include the drug's solubility, dissolution rate, and permeability. For an orally administered drug, the drug must first dissolve in the gastrointestinal fluids before it can be absorbed through the gastrointestinal membranes and enter systemic circulation. The rate of dissolution is often the slowest step and thus rate-limiting for poorly water soluble drugs. Techniques such as reducing particle size, use of salt forms, and amorphous forms can increase dissolution rate and bioavailability.
This document summarizes factors that affect drug absorption including pharmaceutical factors like drug solubility, particle size, polymorphism, and formulation factors as well as patient-related factors like gastric emptying time, gastrointestinal pH, and disease states. Some key pharmaceutical factors discussed are how smaller particle size increases surface area and dissolution rate, amorphous forms have higher solubility than crystalline forms, and solubility of different polymorphs and hydrates can impact absorption. The summary briefly outlines several formulation excipients and how they may influence drug absorption.
1) Pharmaceutical factors like a drug's physicochemical properties, formulation, and dosage form can impact drug absorption. A drug's solubility, dissolution rate, particle size, polymorphism, and salt form all influence absorption.
2) Patient-related physiological factors also affect absorption. Gastric emptying rate, intestinal motility, pH of the GI tract, blood flow to the GI tract, and food intake can impact when and how quickly a drug is absorbed.
3) A drug's ionization state is important as the unionized form is better able to passively diffuse across membranes. A drug's pKa and lipid solubility determine what portion of the drug will be ionized versus unionized based on
This document discusses the pH partition hypothesis which explains drug absorption from the gastrointestinal tract and distribution across biomembranes. It states that a drug must be in its unionized form to be absorbed, and the fraction of a drug that is unionized depends on the drug's dissociation constant (pKa) and the pH of the solution. Weak acids are absorbed in the stomach while weak bases are absorbed in the intestine where they are more likely to be unionized. The document also discusses how a drug's lipid solubility, as indicated by its partition coefficient, affects its absorption, with more lipid soluble drugs generally being better absorbed. It provides examples of how solubility and absorption can be modified through the use of excipients,
Pharmacosomes are colloidal dispersions of drugs that are covalently bound to lipids. They can exist as ultrafine vesicular, micellar, or hexagonal aggregates depending on the chemical structure of the drug-lipid complex. Pharmacosomes have advantages over other drug delivery systems like liposomes in that the drug is covalently bound so there is no leaching and release is controlled. They can be prepared using methods like hand shaking, ether injection, lyophilization, or solvent evaporation. Pharmacosomes are evaluated for complex formation, morphology, solubility, drug-lipid compatibility, drug entrapment, and in vitro drug release.
This document discusses pre-formulation studies, which involve characterizing physicochemical properties of drug substances to provide information useful for developing stable and bioavailable dosage forms. Key aspects covered include determining drug degradation pathways, solubility, hygroscopicity, polymorphism, and thermal properties. The goal of pre-formulation is to understand factors influencing drug performance, stability, bioavailability, and dosage form development.
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TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...Donc Test
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by Stamler, Verified Chapters 1 - 33, Complete Newest Version Community Health Nursing A Canadian Perspective, 5th Edition by Stamler, Verified Chapters 1 - 33, Complete Newest Version Community Health Nursing A Canadian Perspective, 5th Edition by Stamler Community Health Nursing A Canadian Perspective, 5th Edition TEST BANK by Stamler Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Pdf Chapters Download Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Pdf Download Stuvia Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Study Guide Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Ebook Download Stuvia Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Questions and Answers Quizlet Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Studocu Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Quizlet Test Bank For Community Health Nursing A Canadian Perspective, 5th Edition Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Pdf Chapters Download Community Health Nursing A Canadian Perspective, 5th Edition Pdf Download Course Hero Community Health Nursing A Canadian Perspective, 5th Edition Answers Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Ebook Download Course hero Community Health Nursing A Canadian Perspective, 5th Edition Questions and Answers Community Health Nursing A Canadian Perspective, 5th Edition Studocu Community Health Nursing A Canadian Perspective, 5th Edition Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Pdf Chapters Download Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Pdf Download Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Study Guide Questions and Answers Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Ebook Download Stuvia Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Questions Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Studocu Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Quizlet Community Health Nursing A Canadian Perspective, 5th Edition Test Bank Stuvia
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
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Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
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FACTORS INFLUENCING DRUG ABSORPTION THOUGH GIT (1).pptx
1. For Class- B.Pharmacy 6th Semester
Subject- BIOPHARMACEUTICS AND PHARMACOKINETICS (BP604T)
RAMAKANT JOSHI
S chool of Studies in Pharmaceutical S ciences,
Jiwaji University, Gwalior
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INTRODUCTION
A drug injected intravascularly directly enters the
systemic circulation and exerts its pharmacological
effects. Majority of drugs administered
extravascularly, generally orally. If intended to act
systemically, such drugs can exert their
pharmacological actions only when they come into
blood circulation from their site of application. So,
absorption is an important step.
3. Definition:
The process of movement of unchanged drug from
the site of administration to systemic circulation.
4. Factors affecting absorption
A. Pharmaceutical factors:
1. Physicochemical properties of drug
a. Drug solubility and dissolution rate
b. Particle size and effective surface area
c. Polymorphism and amorphism
d. Pseudopolymorphism(hydrates or solvates)
e. Salt form of the drug
f. Lipophilicity of the drug
g. Drug stability
h. Stereochemical nature of the drug
5. 2. Formulation factors
a. disintegration time
b. manufacturing variables
c. nature and type of dosage form
d. pharmaceutical ingredients (excepients)
e. product age and storage conditions
6. B. Patient related factors
a. age
b. gastric emptying time
c. intestinal transit time
d. gastrointestinal pH
e. diseased states
f. blood flow through the GIT
g. gastrointestinal contents
1.other drugs
2.food
3.fluids
4.other normal G.I contents
h. presystemic metabolism by
1. luminal enzymes
2.gut wall enzymes
3.bacterial enzymes
4. hepatic enzymes
7. a. Drug solubility and dissolution rate
solid dosage form
disintegration
solid drug particles
dissolution (RDS for lipophilic drugs)
drug in solution at absorption site
permeation (RDS for hydrophilic drugs)
drug in the body
8. For Hydrophobic drugs
For Hydrophilic drugs
Dissolution is rate limited step. e.g. Griseofulvin, spironolactone
Permeation is rate limited step. e.g. cromolyn sodium, neomycin.
9.
10. b. Particle size and effective surface area
of drug
Smaller the drug particle, greater the surface area.
surface area
absolute surface area effective surface area
total surface area of
solid surface of particle
area of solid surface exposed to
dissolution medium
11. Smaller the particle size (by micronization) greater is the
effective surface area more intimate contact b/w solid surface
and aq solvent higher is the dissolution rate increase in
absorption efficiency.
Particle size reduction has been used to increase the
absorption of a large number of poorly soluble drugs, such as
bishydroxycoumarin, digoxin, griseofulvin, nitrofurantoin,and
tolbutamide.
Griseofulvin has extremely low aqueous solubility, and
material of normal particle size gave rise to poor and erratic
absorption.
Microsize particles improve absorption, but it is improved
even more when it is formulated in ultramicrosize particles as
a monomolecular dispersion in polyethylene glycol.
12. c.Polymorphism and Amorphism
Many compounds form crystals with different molecular
arrangements, or polymorphs.
These polymorphs may have different physical properties, such
as dissolution rate and solubility.
polymorphs
enantiotropic monotropic
polymorph polymorph
eg: sulphur eg:glyceryl stearates
13. 40 % of all organic compounds – exist in various polymorphic
forms.
70% of barbiturates & 65% of sulphonamides exhibit
polymorphism.
Amorphous form:
These have greater aqueous solubility than the crystaline
forms because the energy required to transfer a molecule from
crystal lattice is greater than that required for non-crystalline
solid .
eg: amorphous form of novobiocin - 10 times more soluble
than crystalline form.
amorphous > metastable> stable
14. d.Hydrates or solvates
The stoichiometric type of adducts where the solvent
molecule are incorporated with the crystal lattice of the
solid are called as solvates.
Trapped solvent is the solvent of crystallisation.
The solvates can exist in diff crystalline forms called as
is
pseudomorphs and the phenomenon
pseudopolymorphism.
When the solvent in association with drug is water, the
solvate is known as hydrate.
15. eg: anhydrous form of theophylline and ampicillin
high aq solubility
dissolve at a faster rate
more bioavailability than their monohydrate &
trihydrate forms
16. e. Salt form of drug
At given pH, the solubility of drug, whether acidic/basic
or its salt, is a constant.
While considering the salt form of drug, pH of the
diffusion layer is imp not the pH of the bulk of the
solution.
For salts of weak acids,
[H+]d < [H+]b
For salts of weak bases,
[H+]d > [H+]b
where [H+]d = [H+] of diffusion layer
[H+]b = [H+] of bulk of the solution
17.
18. Other approach to enhance the dissolution and absorption rate
of certain drugs is by in – situ salt formation
i.e. increasing in pH of microenvironment of drug by
incorporating buffer agent.
e.g: aspirin, penicillin
But sometimes more soluble salt form of drug may result in
poor absorption.
e.g: sodium salt of phenobarbitone and phenobarbitone
tablet of salt of phenobarbitone swelled
it did not get disintegrate
dissolved slowly & results in poor absorption.
19.
20. f.Drug pKa & lipophilicity & GI pH --- pH partition
hypothesis
pH – partition theory states that for drug compounds of molecular
weight more than 100, which are primarily transported across the
biomembrane by passive diffusion,
the process of absorption is governed by
pKa of drug
The lipid solubility of the unionized drug
pH at the absorption site.
21. Amount of drug that exist in unionized form and in ionized form
is a function of pKa of drug & pH of the fluid at the absorption
site and it can be determined by Hendersonhesselbach equation: -
For
,Acidic drugs
pH = pKa + log [ionized form]
[Unionized form]
For
, Basic drugs
pH = pKa + log [unionized form]
[Ionized form]
22. g.Lipophilicity and drug absorption
Ideally for optimum absorption, a drug should have
sufficient aq solubility to dissolve in fluids at absorption site
and lipid solubility (Ko/w) high enough to facilitate the
partitioning of the rug in the lipoidal biomembrane i.e. drug
should have perfect HLB for optimum Bioavailability.
Ko/w = Distribution of drug in organic phase
(octanol) Distribution of drug in aq
phase
As Ko/w i.e. lipid solubility, i.e. partition
coefficient increases percentage drug
absorbed increases.
23.
24.
25. 1. Disintegration time:
Rapid disintegration is important to have a rapid absorption so lower
D.T is required.
Now D.T of tablet is directly proportional to – amount o f binder -
Compression force.
And one thing should be remembered that in vitro disintegration test
gives no means of a guarantee of drugs bioavailability because if the
disintegrated drug particles do not dissolve then absorption is not
possible.
2. Manufacturing variables: -
a) Method of granulation:
Wetgranulation yields a tablet that dissolves faster than those made
by other granulating methods. But wet granulation has several
limitations like formation of crystal bridge or chemical degradation.
Formulation factor
26. Other superior recent method namedAPOC (agglomerative
phase of communition) that involves grinding of drug till
spontaneous agglomeration and granules are prepared with
higher surface area. So tablet made up of this granules have
higher dissolution rate.
b) Compression force:
Higher compression force yields a tablet with greater hardness
and reduced wettability & hence have a long D.T. but on other
hand higher compression force cause crushing of drug particles
into smaller ones with higher effective surface area which in
decrease in D.T.
So effect of compression force should be thoroughly studied on
each formulation.
28. Drug formulations are
designed to provide an
attractive, stable, and
convenient method to use
products. Conventional
dosage forms may be broadly
characterized in order of
decreasing dissolution rate as
solutions, solid solutions,
suspensions, capsules and
tablets, coated capsules and
tablets, and controlled release
formulations.
29. A. Solutions:
Aqueous solutions, syrups,
elixirs, and emulsions do
not present a dissolution
problem and generally
result in fast and often
complete absorption as
compared to solid dosage
forms. Due to their
generally good systemic
availability, solutions are
frequently used as
bioavailability standards
against which other dosage
forms are compared.
30. B.Solid solutions
The solid solution is a
formulation in which
drug is trapped as a solid
solution or
monomolecular
dispersion in a water-
soluble matrix.Although
the solid solution is an
attractive approach to
increase drug absorption,
only one drug,
griseofulvin, is currently
marketed in this form.
31. C.Suspensions:
A drug in a suspension is in solid
form, but is finely divided and hasa
large surface area. Drug particles
can diffuse readily between the
stomach and small intestine so that
absorption is relatively insensitive
to stomach emptying rate.
Adjusting the dose to a patient’s
needs is easier with solutions and
suspensions than with solid dosage
forms. Liquid dosage forms,
therefore, have several practical
advantages besides simple
dissolution rate.
However, they also have some
disadvantages, including greater
bulk, difficulty in handling,and
perhaps reduced stability.
32. D. Capsules and tablets:
These formulations differ from
each other in that material in
capsules is less impacted than in
compressed tablets. Once a
capsule dissolves, the contents
generally disperse quickly. The
capsule material, although water
soluble, can impede drug
dissolution by interacting with the
drug, but this is uncommon.
Tablets generally disintegrate in
stages, first into granules and then
into primary particles. As particle size
decreases, dissolution rate increases
due to of increased surface area.
33. Tablet disintegration was once
considered a sufficient criterion to
predict in vivo absorption.
As a general rule, the bio-
availability of a drug from various
dosage forms decrease in the
following order:
Solutions > Emulsions> Suspensions >
Capsules >Tablets > Coated Tablets >
Enteric coated
Tablets > Sustained Release Products.
34. 4. Pharmaceutical ingredients /
Excipients
More the no. of excepients in dosage form, more complex it
is & greater the potential for absorption and Bioavailability
problems.
Changing an excipient from calcium sulfate to lactose and
increasing the proportion of magnesium silicate, increases
the activity of oral phenytoin.
Systemic availability of thiamine and riboflavin is reduced by
the presence of Fuller’s earth.
Absorption of tetracycline from capsules is reduced
by calcium phosphate due to complexation.
Most of these types of interactions were reported some time
ago and are unlikely to occur in the current environment of
rigorous testing of new dosage forms and formulations.
35. a) Vehicle:
Rate of absorption – depends on its miscibility with biological
fluid.Miscible vehicles (aq or water miscible vehicle) –rapid
absorption e.g. propylene glycol.
Immiscible vehicles - absorption –depends on its partitioning
from oil phase to aq body fluid.
b) Diluents:
Hydrophilic diluents-form the hydrophilic coat around
hydrophobic drug particles –thus promotes dissolution and
absorption of poorly soluble hydrophobic drug.
c) Binders & granulating agent :
Hydrophilic binders – imparts hydrophilic properties to granule
surface – better dissolution of poorly wettable drug. e.g. starch,
gelatin, PVP. More amount of binder – increases hardness of
tablet – decrease dissolution & disintegration
rate.
36. d) Disintegrants
Mostly hydrophilic in nature.
Decrease in amount of disintegrants – significantly lowers
B.A.
e) Lubricants :
Commonly hydrophobic in nature – therefore inhibits
penetration of water into tablet and thus dissolution and
disintegration.
f) Suspending agents/viscosity agent :
Stabilized the solid drug particles and thus affect drug
absorption.
Macromolecular gum forms unabsorbable complex with drug
e.g. Na CMC.
Viscosity imparters – act as a mechanical barrier to diffusion
of drug from its dosage form and retard GI transit of drug.
37. g) Surfactants :
May enhance or retards drug
absorption by interacting with drug
or membrane or both.
Surfactants have been considered
as absorption enhancers, again
mostly in animals.
Polyoxyethylene ethers have been
shown to enhance gastric or rectal
absorption of lincomycin, penicillin,
cephalosporins, and fosfomycin in
rats and rabbits.
However, in humans, oral
polyoxyethylene-20-oleyl ether
resulted in poor and variableinsulin
absorption.
38. In general, unionic surfactants
have little effect on membrane
structure but cationic
Surfactants have been associated
with reversible cell loss and loss of
goblet cells.
Physiologic surfactants – bile
salts – promotes absorption
e.g. Griseofulvin, steroids
It may decrease absorption when
it forms the unabsorbable complex
with drug above CMC.
39. Colourants:
Even a low concentration of water soluble dye can have
an inhibitory effect on dissolution rate of several
crystalline drugs.
The dye molecules get absorbed onto the crystal faces
and inhibit the drug dissolution.
e.g: Brilliant blue retards dissolution of sulfathiazole.
5. Product age and storage conditions :
Product aging and improper storage conditions
adversely affect B.A.
e.g:precipitation of drug in solution decrease rate of
Change in particle size of suspension drug dissolution
& Hardening of tablet & absorption.
40. Patient related factors
Gastric emptying: apart from the dissolution of
drug and its permeation through the bio
membrane,the passage from stomach to small
intestine, called as gastric emptying,can also be a
rate limiting step in absorption because the major
site of drug absorption is intestine.
It is advisable where:
Rapid onset of drug is desired eg:sedatives
Drug not stable in gastric fluids eg:pencillin G
Dissolution occuring in intestine eg:enteric coated
forms
41.
42. Delay in gastric emptying is recommended in particular
where:
Food promotes drug dissolution and absorption
eg: griseofulvin.
The drugs dissolve slowly. Disintegration and dissolution of
dosage form is promoted by gastric fluids.
Gastric emptying is first order process. Several
parameters used to quantify are:
Gastric emptying rate: speed at which stomach contents
empties into intestine.
Gastric emptying time: time required for gastric contents
to empty into small intestine
Gastric emptying t1/2 : time taken for half of the stomach
contents to empty
43. Factors influencing gastric emptying
V
olume of meal: larger the bulk of meals, longer the gastric
emptying time.An initial rapid rate of emptying observedwith
large volume of meal and an initial lag phase in emptying of
small volume of meal.
Since gastric emptying is first order, a plot of volume of
contents remaining in stomach vs time yields a straight line.
Composition of meal:
carbohydrates > proteins> fats
Delayed gastric emptying with fatty meal, is beneficial for the
absorption of poorly soluble drugs like griseofulvin.
44. Physical state and viscosity of meal:
Liquid meals take less than hour to empty whereas a solid
meal may take as long as 6 to 7 hours.
Temperature:
High or low temperature of injested fluid reduces the gastric
emptying.
Gastro intestinal ph:
Retarded at low stomach ph and promoted at high ph. The
inhibitory effect of various acids on emptying decreases with
increase in mol wt, order is:
Hcl > acetic > lactic > tartaric> citric
Electrolytes and osmotic ph: water, isotonic solutions and of
low salt concentration empty rapidly whereas high electrolyte
conentration decreases gastric emptying.
45. Drugs that retard gastric emptying include
Poorly soluble antacids: aluminium hydroxide
Anticholinergics: atropine
Narcotic analgesics: morphine
Tricyclic anti depressents: imipramine
Disease state: like gastroenteritis, gastric ulcer, pyloric stenosis
retard gastric emptying rate.
46. Intestinal transit
Since small intestine is the major site for absorption of most
drugs, long intestinal transit time is desirable for complete
drug absorption.
Intestinal region Transit time
Duodenum 5 min
Jejunum 2 hrs
Ileum 3to 6 hrs
Caecum 0.5 to 1hr
Colon 6 to 12 hrs
47. Delayed transit time is desirable for:
Drugs that dissolve their dosage form.
Drugs that dissolve only in intestine.
Drugs absorbed from specific sites in the intestine.
Laxatives promote the rate of intestinal transit.
Anticholinergic drugs: retard gastric and intestinal transit
promote absorption of poorly soluble drugs
eg:propantheline
48. Gastro intestinal pH
The GI ph generally increases as one moves down the stomach
to the colon and rectum.GI ph influence absorption in several
ways.
Disintegration:
coat dissolves
Enteric coated formulations:
only in intestine followed by disintegration.
Dissolution:
weakly acidic drugs: dissolve rapidly in alkaline ph of
intestine
Weakly basic drugs: dissolve in acidic ph of stomach
49. Absorption: depends on drug pKa and whether its an acidic or
basic drug, GI ph influences drug absorption by determining
amount of drug that would exist in unionised form at the site of
absorption.
Stability: acidic stomach ph- affect degradation of pencillin G
and erythromycin
Can be overcome by preparing prodrugs of such drugs .
eg: carindacillin and erythromycin estolate.
50. Pre systemic metabolism
For a drug administration orally, the 2 main reasons for its
decreased bioavailability are:
a. Decreased absorption and
b. First pass metabolism
The loss of drug through biotransformation by such
eliminating organs during its passage to systemic circulations
called as first pass or presystemic metabolism.
The 4 primary systems which effect presystemic metabolism
of a drug are:
a. Luminal enzymes
c. Bacterial enzymes
b. Gut wall enzymes
d. Hepatic enzymes
51. Luminal enzymes
These are present in gut fluids and include enzymes from
intestinal and pancreatic secretions. latter containhydrolases
which hydrolyse ester drugs.
chloramphenicol palmitate active chloramphenicol, and
which split amide linkages and inactivate proteins.
One approach to
effect oral
absorption of
peptides is
To deliver them to
colon which lack
peptidases
52. * also called as mucosal enzymes
present in stomach, intestine and colon.
eg: sulphasalazine
(drug in ulcerative colitis)
sulphapyridine &
5-aminsalicylic acid
Alcohol dehydrogenase: enzyme of stomach mucosa
inactivates ethanol.
Intestinal mucosa: contains both phase I and phase II
enzymes.
eg: sulphation if ethinyl estradiol .
Colonic mucosa: also contains both phase I and phase II
enzymes.
Bacterial enzymes: colonic generally render a drug more
active or toxic on biotransformation.
hydrolyzation
53. Enzymes hydrolyse conjugates of drugs actively secreted via bile
such as glucoronides of digoxin and oral contraceptives
Hepatic enzymes:
several drugs undergo first pass hepatic metabolism, the highly
extracted ones being isoprenaline, propranolol, alprenolol,
pentoxyphylline, nitroglycerine, diltiazem, lidocaine, morphine
etc.
54. Altered GI motility:
Gastrointestinal diseases and infections:
Two of the intestinal disorders related with
malabsorption syndrome that influence drug availability
are celiac disease and Crohn’s disease.
Crohn’s disease that can alter absorption pattern are
altered gut wall microbial flora, decreased gut surface
area and intestinal transit rate.
GI infections like shigellosis, gastroenteritis, cholera
and food poisoning also result in malabsorption.
55. Gastrointestinal surgery:
Gastrectomy can result in drug dumping in the intestine,
osmotic diarrhea and reduced intestinal transit time.
Cardiovascular diseases:
Several changes associated with congestive cardiac failure
influence bioavailability of a drug.
Hepatic diseases:
Disorders such as hepatic cirrhosis influence bioavailability
mainly of drugs that undergo considerable first-pass hepatic
metabolism.
e.g. propranolol.
56. Food-drug interactions: Presence of food may either delay,
reduce, increase or may not affect drug absorption.
Delayed Decreased Increased Unaffected
Aspirin Pencillins Griseofulvin Methyldopa
Paracetamol Erythromycin Nitrofurantoin Propylthiouracil
Diclofenac Ethanol Diazepam Sulfasomidine
Nitrofurantoin
Dioxin
Tetracyclines
Levodopa
Iron
Actively
absorbed
vitamins
A number of contentscan influence drug absorption as follows:
57. Administration of drug with large fluid volume results in
better dissolution, rapid gastric emptying and enhanced
absorption.
e.g: erythromycin
Interaction of drug with normal GI constituents:
The GIT contains a number of normal constituents such as
mucin, bile salts and enzymes which influence drug
absorption.
Mucin a protective mucopolysaccharide that lines the GI
mucosa, interacts with streptomycin and certain quaternary
ammonium compounds and retards their absorption.
58. Physicochemical interactions are due to :
Adsorption: antidiarrhoeal preparations containing
adsorbents like attapulgite or kaolin-pectin retard
absorption of number of drugs co-administered with
them.
e.g: promazine, linomycin.
Complexation: unabsorbable complexes are formed. e.g:
antacids or mineral substances containing
heavy metals such asAl, Ca+2 , Mg+2 retard absorptionof
tetracycline by forming unabsorbable complexes.
These interactions can be either physicochemical or physiological.
59. Physiological interactions are due to :
Decreased GI transit:
Anticholinergics like propantheline retard GI motility
and promote absorption of drugs like ranitidine and digoxin &
delay absorption of paracetemol and sulphamethoxazole.
Increased gastric emptying:
Metoclopramide promotes GI motility and enhances
absorption of tetracycline, levodopa.