Ph hypothesis
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ph hypothesis for medical,nursing and pharmacy student to identify the drug absorption and its all kinetics related to ph-pka.
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pH partition theory of drug absorption
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
P h partition hypothesis
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.
Clinical significance of be studies
CLINICAL SIGNIFICANCE OF BIOEQUIVALENCE STUDIES, BIOEQUIVALENCE, REASONS TO PERFORM BIOEQUIVALENCE STUDIES , NEED FOR BIOEQUIVALENCE STUDIES, IMPORTANCE OF BIOEQUIVALANCE STUDIES, DETERMINATION OF BIOEQUIVALENCE OF A DRUG PRODUCT, CLINICAL SIGNIFICANCE.
BIOPHARMACEUTIC CONSIDERATIONS IN DRUG PRODUCT DESIGN
BIOPHARMACEUTICS studies the in vitro impact of physicochemical properties of drugs and drug products on delivery to body under normal or pathologic conditions.
Biopharmaceutics links the physical and chemical properties of drug and drug product to their performance, in vivo.
The aim of biopharmaceutics is to adjust the delivery of drug from drug products in such a manner as to provide: optimal therapeutic activity and safety for the patient.
In vitro Dissolution Testing Models
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.
Theories of Dissolution
DISSOLUTION
Dissolution is defined as a process in which a solid substance solubilises in a given solvent.
(i.e. mass transfer from the solid surface to the liquid phase.)
Three Theories:
Diffusion layer model / Film theory
Danckwert’s model / Penetration or Surface renewal theory
Interfacial barrier model / Double barrier or Limited solvation theory
Techniques for enhancement of dissolution rate
The document discusses various techniques to enhance the dissolution rate of drugs, which is important for predicting bioavailability. It describes the process of dissolution and factors that influence the rate based on the Noyes-Whitney equation. Several methods are covered, including increasing surface area through particle size reduction, using surfactants, solid dispersions, polymorphism, molecular encapsulation, salt formation, and nanosuspensions. Enhancing dissolution rate can improve drug efficacy by increasing bioavailability.
PHARMACOKINETICS: BASIC CONSIDERATION & PHARMACOKINETIC MODELS
Plasma Drug Concentration Time Profile
Pharmacokinetic Parameter
Pharmacodynamic Parameter
Zero, First Order & Mixed Order Kinetic
Rates & Order Of Kinetics
Pharmacokinetic Models
Application Of Pharmacokinetic
Recommended
pH partition theory of drug absorption
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
P h partition hypothesis
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.
Clinical significance of be studies
CLINICAL SIGNIFICANCE OF BIOEQUIVALENCE STUDIES, BIOEQUIVALENCE, REASONS TO PERFORM BIOEQUIVALENCE STUDIES , NEED FOR BIOEQUIVALENCE STUDIES, IMPORTANCE OF BIOEQUIVALANCE STUDIES, DETERMINATION OF BIOEQUIVALENCE OF A DRUG PRODUCT, CLINICAL SIGNIFICANCE.
BIOPHARMACEUTIC CONSIDERATIONS IN DRUG PRODUCT DESIGN
BIOPHARMACEUTICS studies the in vitro impact of physicochemical properties of drugs and drug products on delivery to body under normal or pathologic conditions.
Biopharmaceutics links the physical and chemical properties of drug and drug product to their performance, in vivo.
The aim of biopharmaceutics is to adjust the delivery of drug from drug products in such a manner as to provide: optimal therapeutic activity and safety for the patient.
In vitro Dissolution Testing Models
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.
Theories of Dissolution
DISSOLUTION
Dissolution is defined as a process in which a solid substance solubilises in a given solvent.
(i.e. mass transfer from the solid surface to the liquid phase.)
Three Theories:
Diffusion layer model / Film theory
Danckwert’s model / Penetration or Surface renewal theory
Interfacial barrier model / Double barrier or Limited solvation theory
Techniques for enhancement of dissolution rate
The document discusses various techniques to enhance the dissolution rate of drugs, which is important for predicting bioavailability. It describes the process of dissolution and factors that influence the rate based on the Noyes-Whitney equation. Several methods are covered, including increasing surface area through particle size reduction, using surfactants, solid dispersions, polymorphism, molecular encapsulation, salt formation, and nanosuspensions. Enhancing dissolution rate can improve drug efficacy by increasing bioavailability.
PHARMACOKINETICS: BASIC CONSIDERATION & PHARMACOKINETIC MODELS
Plasma Drug Concentration Time Profile
Pharmacokinetic Parameter
Pharmacodynamic Parameter
Zero, First Order & Mixed Order Kinetic
Rates & Order Of Kinetics
Pharmacokinetic Models
Application Of Pharmacokinetic
Drug interaction
Thank you for the presentation on drug interactions. I appreciate you sharing your knowledge on this important topic.
M pharm dissolution
1. Dissolution is the process by which a solid substance dissolves in a solvent to form a solution. The rate of dissolution depends on factors like temperature, solvent composition, and the liquid/solid interface area.
2. There are several theories that describe the drug dissolution process, including the diffusion layer model, penetration or surface renewal theory, and interfacial barrier model. The most common model is the diffusion layer model, which involves the formation of a saturated film at the solid/liquid interface and diffusion of the drug through this layer.
3. Key factors that affect drug dissolution include the solubility and permeability of the drug substance, the pH and volume of the dissolution medium, and the design of
METHOD OF RESIDUALS
This document presents information on estimating the absorption rate constant using the method of residuals. It discusses absorption and compartment models, outlines the steps of the method of residuals for a one compartment model, and notes considerations like lag time, flip-flop phenomena, and applications and limitations of the method. The method involves plotting drug concentrations over time, obtaining slopes for the terminal and residual lines to determine the absorption and elimination rate constants. It is best suited for rapidly absorbed drugs following one-compartment kinetics.
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Invitro dissolution
The document discusses invitro dissolution testing of drugs. It defines dissolution rate and invitro dissolution tests as tests used to measure the rate and extent of dissolution of a drug from its formulation under specified conditions. Key factors in designing dissolution tests include the apparatus used, dissolution medium properties, and process parameters. Common apparatuses include basket, paddle, reciprocating cylinder, and flow-through cell methods. Dissolution testing provides important information on a drug's in vivo performance and quality control.
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This document discusses large volume parenterals (LVPs), which are intravenous solutions intended for administration of more than 100 mL. It describes the characteristics, containers, labeling requirements, commonly used solutions like sodium chloride, dextrose, Ringer's solution and lactated Ringer's solution. It also discusses types of LVPs including electrolyte, carbohydrate, and nutritional solutions. Large volume parenteral containers can be plastic bags or glass bottles. Total parenteral nutrition solutions, cardioplegia solutions, peritoneal dialysis solutions, and irrigating solutions are also summarized. Formulation considerations for LVPs like drug-excipient compatibility, selection of containers, solubility of active ingredients, and pH are highlighted.Pharmacokinetic models
This document discusses various approaches used to model pharmacokinetics. It describes compartment models, physiological models, and distributed parameter models that can be used to mathematically describe drug absorption, distribution, metabolism and excretion over time. It also discusses model-independent or non-compartmental analysis, which does not require assumptions about specific compartment models. Compartment models include mammillary and catenary models. Physiological models group tissues into compartments based on similar perfusion properties. Distributed parameter models account for variations in organ blood flow and drug diffusion.
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IVIVC
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This document discusses in vitro dissolution testing methods. It defines dissolution as the process by which a solid substance solubilizes in a solvent, and dissolution rate as the amount of drug substance that goes into solution per unit time under standardized conditions. It then describes 7 common apparatus used for in vitro dissolution testing according to pharmacopeial standards, including the rotating basket, paddle, reciprocating cylinder, flow through cell, paddle over disk, rotating cylinder, and reciprocating disk methods. Each apparatus has distinct advantages and disadvantages for testing different drug products and dosage forms.
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Dissolution method and ivivc by ranjeet singh
The document discusses dissolution testing methods for oral drug formulations. It describes dissolution as a mass transfer process involving interactions at solute-solute, solute-solvent, and solvent-solvent interfaces. Official dissolution testing methods specified by regulatory agencies include the rotating basket, paddle, flow-through, reciprocating cylinder, paddle over disk, rotating cylinder, and reciprocating disk methods. Non-official methods described for specific dosage forms include the rotating bottle method for sustained release formulations and dialysis systems for poorly soluble drugs. The document also discusses the importance of establishing in vitro-in vivo correlations to ensure batch uniformity and aid new drug development.
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This document discusses bioequivalence studies, which compare the bioavailability of generic drugs to their branded counterparts. It covers key aspects of bioequivalence protocols such as study design, population, procedures, and data analysis. The main goals are to establish that a generic drug's absorption and exposure levels are equivalent to the reference brand name drug. Proper study design and statistical analysis are required for regulatory approval and to demonstrate therapeutic equivalence between products.
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The document discusses various aspects of bioequivalence studies including study designs and evaluation. It describes four main study designs - pilot studies, replicate designs, non-replicate designs, and food-effect studies. It also discusses evaluating bioequivalence through comparative pharmacokinetic studies, pharmacodynamic studies, clinical trials, in vitro dissolution testing, and other approaches. The key aspects covered are parameters for determining bioequivalence like AUC and Cmax, study considerations for highly variable drugs, and the role of in vitro tests in bioequivalence assessments.
Dissolution study-Dissolution studies Factor affecting dissolution and Invitr...
Dissolution study-Dissolution studies Factor affecting dissolution and Invitr...DRx.Yogesh Chaudhari
This document discusses dissolution, which is the process by which a solid substance solubilizes in a solvent to form a solution. It is affected by various factors related to the chemical properties of the drug and formulation, as well as the testing conditions. The rate of dissolution can be modeled using theories like the diffusion layer model. Dissolution testing is important for optimization, quality control, and showing bioequivalence between batches. Common techniques to increase dissolution rate include reducing particle size, forming salts, selecting appropriate excipients, and processing methods like wet granulation.Organic
This document discusses acid-base properties of drugs. Most drugs are classified as acids or bases, with their acid-base properties influencing distribution and partitioning in the body. The pKa value indicates the pH at which 50% of the drug is ionized and is important for predicting reactions and solubility. The Henderson-Hasselbalch equation can be used to calculate pH for weak acids, bases, and buffers. Whether a drug is an acid or base depends on its functional groups, not its pKa value alone. Calculating percentage ionization using pKa allows optimizing a drug's solubility based on pH.
20.-physicochemical-properties-determination-1.pdf
The document discusses several key physicochemical properties that influence a drug's biological activity, including:
1. Partition coefficient, which measures a drug's relative solubility in water vs. lipid and predicts its distribution in the body.
2. Acidity and basicity, with ionization affecting absorption, transport, binding, and elimination. The Henderson-Hasselbalch equation calculates the percentage of a drug in its ionized and unionized forms.
3. Steric factors like a drug's bulk, size, and shape, which can either hinder or help its interaction with receptors and enzymes. A drug's physicochemical properties are crucial to its ability to reach biological targets.
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1. Dissolution is the process by which a solid substance dissolves in a solvent to form a solution. The rate of dissolution depends on factors like temperature, solvent composition, and the liquid/solid interface area.
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This document presents information on estimating the absorption rate constant using the method of residuals. It discusses absorption and compartment models, outlines the steps of the method of residuals for a one compartment model, and notes considerations like lag time, flip-flop phenomena, and applications and limitations of the method. The method involves plotting drug concentrations over time, obtaining slopes for the terminal and residual lines to determine the absorption and elimination rate constants. It is best suited for rapidly absorbed drugs following one-compartment kinetics.
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Definition, importance, objectives, methods to compare, applications, advantages and disadvantages, references.
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The document discusses invitro dissolution testing of drugs. It defines dissolution rate and invitro dissolution tests as tests used to measure the rate and extent of dissolution of a drug from its formulation under specified conditions. Key factors in designing dissolution tests include the apparatus used, dissolution medium properties, and process parameters. Common apparatuses include basket, paddle, reciprocating cylinder, and flow-through cell methods. Dissolution testing provides important information on a drug's in vivo performance and quality control.
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This document discusses various approaches used to model pharmacokinetics. It describes compartment models, physiological models, and distributed parameter models that can be used to mathematically describe drug absorption, distribution, metabolism and excretion over time. It also discusses model-independent or non-compartmental analysis, which does not require assumptions about specific compartment models. Compartment models include mammillary and catenary models. Physiological models group tissues into compartments based on similar perfusion properties. Distributed parameter models account for variations in organ blood flow and drug diffusion.
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Bioequivalence studies for various drug molecules formulated in the market is outlined in this presentation.
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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.
IVIVC
An in-vitro in-vivo correlation (IVIVC) has been defined by the U.S. Food and Drug Administration (FDA) as "a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response".
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In vitro dissolution testing methods
This document discusses in vitro dissolution testing methods. It defines dissolution as the process by which a solid substance solubilizes in a solvent, and dissolution rate as the amount of drug substance that goes into solution per unit time under standardized conditions. It then describes 7 common apparatus used for in vitro dissolution testing according to pharmacopeial standards, including the rotating basket, paddle, reciprocating cylinder, flow through cell, paddle over disk, rotating cylinder, and reciprocating disk methods. Each apparatus has distinct advantages and disadvantages for testing different drug products and dosage forms.
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The document discusses dissolution testing methods for oral drug formulations. It describes dissolution as a mass transfer process involving interactions at solute-solute, solute-solvent, and solvent-solvent interfaces. Official dissolution testing methods specified by regulatory agencies include the rotating basket, paddle, flow-through, reciprocating cylinder, paddle over disk, rotating cylinder, and reciprocating disk methods. Non-official methods described for specific dosage forms include the rotating bottle method for sustained release formulations and dialysis systems for poorly soluble drugs. The document also discusses the importance of establishing in vitro-in vivo correlations to ensure batch uniformity and aid new drug development.
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This document provides an overview of enteric coating polymers that are used to protect acid-labile drugs and ensure optimal drug absorption. It discusses various categories of enteric coating polymers including polymethacrylates (Eudragit), cellulose esters, and polyvinyl derivatives. Key points include: Eudragit polymers are commonly used methacrylic acid copolymers that are insoluble in gastric fluid but dissolve in the intestine. Cellulose esters like cellulose acetate phthalate are also widely employed. These polymers form films that protect the drug core from gastric conditions and dissolve above pH 6, allowing drug release in the intestines. The solubility and properties of different enteric coating polymers allow controlling
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This document discusses gastroretentive drug delivery systems (GRDDS), which are oral dosage forms designed to remain in the stomach for an extended period of time to prolong drug release. It covers the rationale for using GRDDS, factors controlling gastric residence time, and various approaches for prolonging gastric retention including floating systems, high-density systems, and bioadhesive or magnetic systems. Floating systems include non-effervescent and effervescent types that float due to low density or gas generation. High-density systems do not float but remain in the stomach through bioadhesion, magnetic forces, swelling to a large size, or raft formation on gastric fluids.bioequivalence studies - advanced biopharmaceutics
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bioequivalence studies - advanced biopharmaceutics
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Bioequivalence studies ( Evaluation and Study design)
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Similar to Ph hypothesis
Organic
This document discusses acid-base properties of drugs. Most drugs are classified as acids or bases, with their acid-base properties influencing distribution and partitioning in the body. The pKa value indicates the pH at which 50% of the drug is ionized and is important for predicting reactions and solubility. The Henderson-Hasselbalch equation can be used to calculate pH for weak acids, bases, and buffers. Whether a drug is an acid or base depends on its functional groups, not its pKa value alone. Calculating percentage ionization using pKa allows optimizing a drug's solubility based on pH.
20.-physicochemical-properties-determination-1.pdf
The document discusses several key physicochemical properties that influence a drug's biological activity, including:
1. Partition coefficient, which measures a drug's relative solubility in water vs. lipid and predicts its distribution in the body.
2. Acidity and basicity, with ionization affecting absorption, transport, binding, and elimination. The Henderson-Hasselbalch equation calculates the percentage of a drug in its ionized and unionized forms.
3. Steric factors like a drug's bulk, size, and shape, which can either hinder or help its interaction with receptors and enzymes. A drug's physicochemical properties are crucial to its ability to reach biological targets.
Preformulation
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.
Buffer system for bph
This document discusses different buffer systems in the human body that help maintain pH levels. It describes three main buffer systems:
1) The bicarbonate buffer system in plasma uses sodium bicarbonate and carbonic acid to act as a proton donor and acceptor, keeping blood pH at 7.4.
2) The phosphate buffer system is found in the cytoplasm of cells and uses sodium phosphate salts to buffer carbon dioxide levels in red blood cells.
3) Proteins in the body contain both acidic and basic groups that allow them to act as buffers, accepting or donating protons to resist pH changes when acids or bases are introduced.
Ruchi rawat, romit vaishnav presentation on ph partition
basic concept,digram showing drug transfer from membrane, ph partition throry, deviations,drug pka and GI ph, equations on weak acid and weak base, deviations from ph-partition theory.
Ionisation constant
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.
Partition coefficient
The partition coefficient is the ratio of concentrations of a compound between two immiscible solvents at equilibrium. For drug delivery, the lipophilic/hydrophilic balance affects the rate and extent of drug absorption, as biological membranes are lipoidal in nature and passively absorbed drugs' rate of transfer is directly related to their lipophilicity. Drug classes are determined based on factors like pKa and LogP values, with class affecting absorption. Parameters like pH, pKa, and lipid solubility of un-ionized drugs influence the gastrointestinal absorption of weakly acidic or basic drugs.
pH stability profile
1. A pH-rate profile plots the log of the observed degradation rate constant (kobs) versus pH. It identifies the pH at which a drug is most stable by determining how the degradation rate changes with pH.
2. Just a 1 pH unit shift can cause a 10-fold change in a drug's degradation rate. pH-rate profiles are constructed to locate the optimum pH range for maximum stability.
3. pH-rate profiles can indicate whether a drug's degradation is catalyzed by acid, base, or water. More complex profiles result for drugs with ionizable groups, as the degradation of each ionized form must be considered.
pka and acid dissociation constant
Introduction : Dissociation constant.
Dissociation of molecules in water.
Acid dissociation constant.
Theoretical background.
Conjugate acid & Conjugate base.
Handerson-Hasselbalch equation.
Factors affecting pKa values.
Experimental determination.
Application & Significance.
Conclusion.
References.
CHE 101_Buffers_DRK.pdf
Buffer solutions resist changes in pH upon the addition of acids or bases. They contain a weak acid and its conjugate base, or a weak base and its conjugate acid, which neutralize added H3O+ or OH- ions. The Henderson-Hasselbalch equation relates the pH of a buffer to the ratio of conjugate acid and base concentrations. Blood buffers maintain pH between 7.35-7.45 using carbonic acid and bicarbonate ion equilibriums to neutralize added acids or bases and regulate CO2 and O2 levels in the body.
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This document discusses key concepts in solubility and dissolution including:
- Definitions of solubility, saturated solutions, and intrinsic solubility. Solubility is affected by temperature, pressure, and particle size.
- The importance of solubility and dissolution in drug absorption and bioavailability. Modification techniques to improve solubility including changes in particle size, crystal habit, chemical modifications, and use of adjuvants.
- Explanations of partition coefficient (LogP/LogKo/w), pKa, and the Henderson-Hasselbalch equation and how they relate to a drug's ionization, absorption, and excretion. pKa indicates a drug's acid or base strength and ionized state
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This document discusses acid-base balance and pH. It defines pH as the negative log of the hydrogen ion concentration. The pH scale ranges from 0 to 14, with values below 7 being acidic and above 7 being basic. The body maintains acid-base balance through buffer systems like bicarbonate and proteins, and respiratory and renal compensation mechanisms. Disturbances in acid-base balance can cause metabolic acidosis, metabolic alkalosis, respiratory acidosis, or respiratory alkalosis.
Acid base balance - Regulation of pH of body fluids
The document summarizes acid-base balance and the regulation of pH in the body. It discusses how acids and bases are defined, the strengths of different acids, and how the pH scale is used to measure hydrogen ion concentration. The three main mechanisms for regulating pH are chemical buffering systems like bicarbonate-carbonic acid and phosphate buffers, respiratory regulation through breathing, and renal regulation where the kidneys excrete acids and regulate bicarbonate levels. Together, these mechanisms maintain blood pH within a narrow range.
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This document discusses buffer solutions, including their definition, examples, and mechanisms of action. It defines a buffer as a solution that resists changes to its pH when small amounts of acid or base are added. Common buffer systems include carbonic acid/sodium bicarbonate and monosodium phosphate/disodium phosphate. The Henderson-Hasselbach equation relates the pH of a buffer solution to the ratio of its conjugate acid and base forms and their pKa values. Buffers in the body include bicarbonate, phosphate, and protein buffers that help maintain blood pH within a narrow range.
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Ph hypothesis
- 2. 08/05/18 2 pH is the logarithm of hydrogen and hydroxyl ion concentration. pH scale is present between 0 to 14. ACIDIC BASIC BHARDWAJ CLASS
- 3. 08/05/18 3 pKa is the negative logarithm of the dissociation constant of a drug. According to Henderson -Hasselbalch equation – pH = pKa – log ( ionized/unionized)………..for a weak acid. pH = pKa – log ( unionized/ionized)………...for a weak base. pH = pKa – log ( ionized/unionized)………… .1 when ionized = unionized equation change into pH = pKa – log ( 1/1)………………….2 Or pH = pKa – log 1 (log 1 = 0) pH = pKa ………………………………3 From the equation 3 the pKa is Ph where the ionized part is equal to unionized part. BHARDWAJ CLASS
- 4. 08/05/18 4 MOST DRUG MOLECULES ARE EITHER WEAK ACIDS OR WEAK BASES. Very weak acidic drug (pKa>8) e.g. is pentobarbitol ,hexobarbitol. Strong acidic drug (pKa <2.5) e.g. is disodium cromoglycate. BHARDWAJ CLASS
- 5. 08/05/18 5 This theory given by Brodie et.al. This is based on the assumption that the gastrointestinal /blood barrier acts as a lipid Barrier toward weak electrolyte drugs which are absorbed by passive diffusion. The gastrointestinal /blood barrier is permeable to the non-ionized drug form and impermeable to ionized form. Thus process of absorption is depend on THE IONIZAION AND UNIONIZATION STATE OF DRUG. BHARDWAJ CLASS
- 6. 08/05/18 6 According to Henderson -Hasselbalch equation – pH = pKa – log ( ionized/unionized)………..for a weak acid. pH = pKa – log ( unionized/ionized)………...for a weak base. Example – calculate the part of drug absorption of drug having pKa 4. Solution – if the drug have pKa = 4 In gastric fluid (where ph is in the range of 2 to 4.) and in blood (Ph=7.4) In gastric fluid (assume that pH is 1.2) pH = pKa – log ( ionized/unionized)………..for a weak acid 1.2 = 4- log (ionized/unionized) 1.2-4 = log (ionized/unionized) -2.8 = log (ionized/unionized) Antilog (-2.8) = (ionized/unionized) BHARDWAJ CLASS
- 7. 08/05/18 7 Example – calculate the part of drug absorption of drug having pKa 4. Solution – if the drug have pKa = 4 In gastric fluid (where ph is in the range of 2 to 4.) and in blood (Ph=7.4) pH = pKa – log ( ionized/unionized)………..for a weak acid STOMACH pH=1.2 BLOOD (Ph=7.4) ionized ionizedunionized unionized BHARDWAJ CLASS