This document discusses factors that affect drug absorption in the gastrointestinal (GI) tract. It covers pharmaceutical factors like a drug's solubility, particle size, salt form, and polymorphism/amorphism, which can impact dissolution rate and absorption. It also discusses patient-related factors like age, GI pH, transit time, and disease status. Key pharmaceutical factors that influence drug absorption are solubility, dissolution rate, and factors that impact effective surface area like particle size.
The document discusses suspensions, which are two-phase systems composed of solid particles dispersed in a liquid. Suspensions can be classified based on particle size as molecular, colloidal, or coarse dispersions. They can also be classified as flocculated or deflocculated based on how the particles interact. Factors like particle size, viscosity, density, and interfacial properties affect suspension stability. Common methods for producing suspensions include precipitation, dispersion, and controlled flocculation. The stability of suspensions is evaluated through sedimentation volume, degree of flocculation, and zeta potential measurements. Equipment like colloid mills and ultrasonic devices can be used to formulate suspensions.
This document discusses various solubilization techniques for improving the solubility of poorly soluble drugs, including physical and chemical modifications. Under physical modifications, it covers crystal modification techniques like polymorphism and salt formation. It also discusses particle size reduction methods like micronization, nanonization, and production of nanosuspensions. Other techniques covered are drug dispersion in carriers through solid solutions, eutectic mixtures and solid dispersions. It also discusses solubilization using surfactants, complexation, and chemical modifications. The techniques discussed aim to improve drug dissolution rates and oral absorption of class II drugs limited by solubility.
This document discusses drug dissolution, including definitions, theories, mechanisms, factors affecting dissolution, intrinsic dissolution rate, and in-vitro dissolution testing models. It defines dissolution as the mass transfer of a solid substance into a liquid solvent. The key theories discussed are the diffusion layer model, Danckwert's penetration theory, and the interfacial barrier model. Factors affecting dissolution include properties of the drug, test conditions, and dosage form characteristics. Common in-vitro dissolution testing models include non-sink and sink methods that utilize natural or forced convection with varying degrees of agitation.
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.
Techniques for enhancement of dissolution rateSagar Savale
The document discusses various techniques to enhance the dissolution rate of drugs, which is important for predicting bioavailability. It describes the process of dissolution and factors that influence the rate based on the Noyes-Whitney equation. Several methods are covered, including increasing surface area through particle size reduction, using surfactants, solid dispersions, polymorphism, molecular encapsulation, salt formation, and nanosuspensions. Enhancing dissolution rate can improve drug efficacy by increasing bioavailability.
The document discusses suspensions, which are two-phase systems composed of solid particles dispersed in a liquid. Suspensions can be classified based on particle size as molecular, colloidal, or coarse dispersions. They can also be classified as flocculated or deflocculated based on how the particles interact. Factors like particle size, viscosity, density, and interfacial properties affect suspension stability. Common methods for producing suspensions include precipitation, dispersion, and controlled flocculation. The stability of suspensions is evaluated through sedimentation volume, degree of flocculation, and zeta potential measurements. Equipment like colloid mills and ultrasonic devices can be used to formulate suspensions.
This document discusses various solubilization techniques for improving the solubility of poorly soluble drugs, including physical and chemical modifications. Under physical modifications, it covers crystal modification techniques like polymorphism and salt formation. It also discusses particle size reduction methods like micronization, nanonization, and production of nanosuspensions. Other techniques covered are drug dispersion in carriers through solid solutions, eutectic mixtures and solid dispersions. It also discusses solubilization using surfactants, complexation, and chemical modifications. The techniques discussed aim to improve drug dissolution rates and oral absorption of class II drugs limited by solubility.
This document discusses drug dissolution, including definitions, theories, mechanisms, factors affecting dissolution, intrinsic dissolution rate, and in-vitro dissolution testing models. It defines dissolution as the mass transfer of a solid substance into a liquid solvent. The key theories discussed are the diffusion layer model, Danckwert's penetration theory, and the interfacial barrier model. Factors affecting dissolution include properties of the drug, test conditions, and dosage form characteristics. Common in-vitro dissolution testing models include non-sink and sink methods that utilize natural or forced convection with varying degrees of agitation.
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.
Techniques for enhancement of dissolution rateSagar Savale
The document discusses various techniques to enhance the dissolution rate of drugs, which is important for predicting bioavailability. It describes the process of dissolution and factors that influence the rate based on the Noyes-Whitney equation. Several methods are covered, including increasing surface area through particle size reduction, using surfactants, solid dispersions, polymorphism, molecular encapsulation, salt formation, and nanosuspensions. Enhancing dissolution rate can improve drug efficacy by increasing bioavailability.
This document discusses dissolution, which is defined as the process by which a solid substance solubilizes in a given solvent. Key points include:
- Drugs are classified into BCS classes based on their solubility and permeability. The four classes are high/high, high/low, low/high, and low/low.
- Noyes-Whitney and Hixson-Crowell equations describe dissolution kinetics under non-sink and sink conditions. Factors like surface area, diffusion coefficient, and concentration gradients impact dissolution rate.
- In vitro dissolution testing uses apparatus like baskets, paddles, and flow-through cells per BP and USP methods to simulate in vivo conditions and assess
It includes Introductory part about what is Dissolution...then Mechanism of Dissolution is elaborated...Theories of Dissolution also given..It also includes Factors affecting Dissolution profile..Along with References given below for easily searching..
The document discusses dissolution as a tool in pharmaceutics. It defines dissolution as the process where a solid substance solubilizes in a solvent, transferring from the solid surface to the liquid phase. This is the rate-determining step for poorly soluble drugs. The document discusses three main mechanisms of dissolution - the diffusion layer model, Danckwert's model, and the interfacial barrier model. It also covers factors influencing dissolution such as drug properties, apparatus factors, and dissolution media properties. Finally, it provides details on three common dissolution apparatus - the basket, paddle, and reciprocating cylinder methods.
This document discusses various parameters used to characterize drug release from pharmaceutical formulations. It describes diffusion parameters defined by Higuchi's equation and plots. Dissolution parameters like the effects of agitation, pH, temperature, and medium properties are outlined. Pharmacokinetic parameters including Cmax, Tmax, and AUC are defined. The Heckel equation is presented as a method to analyze powder compaction. Similarity factors f1 and f2 are introduced to compare dissolution profiles. The Higuchi and Korsmeyer-Peppas models for drug release are presented.
The document discusses various methods to improve drug solubility including physical modifications like particle size reduction through micronization or formation of nanosuspensions, modification of crystal habit through polymorphism, and drug dispersion in carriers through techniques like solid dispersions. It also discusses chemical modifications such as changing pH, use of buffers, and derivatization. Other methods covered are complexation, solubilization by surfactants to form microemulsions, co-crystallization, cosolvency, hydrotrophy, and solvent deposition. The biopharmaceutical classification system relating solubility and permeability to drug absorption is also summarized.
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.
The document discusses different methods of microencapsulation including air suspension, coacervation, multiorifice centrifugal process, spray drying, and pan coating. It provides details on the working mechanisms and variables that affect each process. Microencapsulation can be used to encapsulate solids, liquids, or gases to properties such as shelf life, taste, and controlled release profiles.
DISSOLUTION AND FACTORS AFFECTING DISSOLUTIONDiksha Tapsale
Dissolution testing is used to determine how quickly an active ingredient is released from its solid dosage form into solution. There are many factors that can affect the dissolution rate, including properties of the drug substance, formulation excipients, processing methods, test apparatus parameters, and test conditions. Some key factors are the drug's particle size, solubility, solid state, salt form, excipient types and amounts, compression force, storage conditions, apparatus design features, stirring rate, temperature, and dissolution medium properties such as pH and viscosity. Careful control and standardization of these factors is important for obtaining reproducible dissolution test results.
This document discusses dissolution, which refers to the process by which a solid drug product dissolves into solution. It describes the film theory of dissolution, where a saturated film forms at the solid-liquid interface and drug diffusion through this film is the rate-determining step. Factors that affect dissolution are also outlined, including drug properties like solubility and particle size, as well as dosage form properties and test parameters. Equations for describing dissolution kinetics like the Noyes-Whitney and Hixson-Crowell cube root models are provided. Intrinsic dissolution rate, which measures dissolution under standardized conditions, is also defined.
The document provides an overview of pre-formulation, which involves determining the physicochemical properties of a drug substance prior to developing a dosage form. It discusses the goals of pre-formulation to formulate an efficacious dosage form with good bioavailability. The protocol involves characterizing the physical, chemical, solubility, stability and compatibility properties of the drug. Key aspects covered include polymorphism, hygroscopicity, particle size, solubility, dissolution, stability in solution and solid state, and compatibility with excipients. The information guides subsequent formulation development.
Phase solubility analysis and pH solubility profileMohit Angolkar
A Brief presentation on the topic- phase solubility analysis and pH solubility profile, which covers the following aspects:
- Solubility introduction
- importance of solubility
- factors influencing solubility
- Phase solubility analysis introduction
- method of analysis
- purification technique
- introduction to pH solubility profile.
Dissolution by Dr. Neeraj Mishra professor pharmaceuticsNeeraj Mishra
The document discusses dissolution, which is the process by which a solid substance enters the solvent phase to form a solution. Dissolution is important for drug absorption from oral dosage forms and can be the rate-limiting step. Dissolution testing is used for quality control, formulation development, and correlating in vitro dissolution to in vivo bioavailability. Theories of dissolution include diffusion layer models and surface renewal models. Factors that affect dissolution include drug properties, dosage form factors, particle size, polymorphism, salt formation, and lipid solubility.
This document discusses solubility and various techniques to improve drug solubility. It defines solubility and solubilization. It notes that drug effectiveness depends on solubility and bioavailability. It then describes techniques like spray freezing into liquid, ultra-rapid freezing, kneading, co-precipitation, and use of solubilizing agents to improve drug solubility. These techniques are aimed at developing drugs with improved solubility and permeability.
This document discusses solubility of drugs from the perspectives of a medicinal chemist and pharmaceutical scientist. From the medicinal chemist perspective, it discusses Lipinski's rule of five for predicting solubility and permeability. It also discusses methods for calculating absorption parameters and predicting aqueous solubility, such as the Moriguchi method for calculating logP. From the pharmaceutical scientist perspective, it outlines various techniques for enhancing drug solubility, including particle size reduction through micronization or nanosuspension, modifying crystal habit through polymorphs or complexes, and chemical modifications through prodrugs or buffer systems. Overall, the document provides an overview of key considerations and approaches for optimizing drug solubility from different scientific viewpoints.
ROLE OF DOSAGE FORM IN GASTRO-INTESTINAL ABSORPTION Ankit Malik
The document discusses how the dosage form impacts drug absorption in the gastrointestinal tract. It summarizes that solutions show the fastest and most complete absorption as they do not have dissolution problems. Suspensions also absorb relatively quickly due to their small particle size. Capsules and tablets must undergo dissolution and disintegration processes first. Coated tablets have an additional step of the coating dissolving or disrupting before drug absorption can occur. The dosage form selection can make over a 60-fold difference in a drug's absorption rate or extent.
The document provides an overview of drug dissolution including:
- Definitions of dissolution rate and intrinsic dissolution rate.
- Theories of drug dissolution including the diffusion layer model, Danckwert's model, and the interfacial barrier model.
- Factors that affect drug dissolution related to the physicochemical properties of drugs, drug product formulation, processing factors, dissolution apparatus and test parameters.
- Importance and applications of drug dissolution testing in product development, quality assurance, stability assessment, and biowaivers.
Formulation factors affecting drug absorptionshikha singh
This presentation discusses formulation factors that affect drug absorption. It identifies manufacturing variables like compression force during tablet production and granulation methods. It also discusses the influence of pharmaceutical ingredients like excipients, vehicles, diluents, and surfactants. Finally, it examines how the nature and type of the dosage form, such as solutions, suspensions, capsules and tablets, can impact drug absorption. The goal is to understand these formulation factors to develop dosage forms that allow drugs to be effectively absorbed and exert their pharmacological effects.
This presentation provides an detailed information about dissolution study. Furthermore, it provides various dissolution theories, application , various dissolution apparatus etc.
Dissolution parameters of a dosage formMOHAMMAD ASIM
Dissolution parameters include the effect of agitation, dissolution fluid, pH, surface tension, viscosity, additives, medium volume, deaeration, and temperature. Dissolution is the process where a solid dissolves into a liquid solvent via mass transfer. Key factors that influence dissolution rates include the pH and properties of the dissolution medium, agitation level, drug properties, and ensuring sink conditions. Maintaining proper test conditions such as temperature, medium volume, and sink conditions is important for obtaining reproducible and discriminating results.
This document discusses drug dissolution, which is the process by which a solid drug solubilizes in a solvent. It defines dissolution rate and describes the steps involved in drug release from tablets. Theories of dissolution including diffusion layer theory, Danckwert's model, and interfacial barrier theory are covered. Factors that affect dissolution such as drug properties, dosage form characteristics, and patient factors are also discussed. Common apparatus and methods used for conducting dissolution tests are presented. The document concludes that in vitro dissolution testing can help ensure batch-to-batch consistency and predict in vivo bioavailability.
This document discusses dissolution, which is defined as the process by which a solid substance solubilizes in a given solvent. Key points include:
- Drugs are classified into BCS classes based on their solubility and permeability. The four classes are high/high, high/low, low/high, and low/low.
- Noyes-Whitney and Hixson-Crowell equations describe dissolution kinetics under non-sink and sink conditions. Factors like surface area, diffusion coefficient, and concentration gradients impact dissolution rate.
- In vitro dissolution testing uses apparatus like baskets, paddles, and flow-through cells per BP and USP methods to simulate in vivo conditions and assess
It includes Introductory part about what is Dissolution...then Mechanism of Dissolution is elaborated...Theories of Dissolution also given..It also includes Factors affecting Dissolution profile..Along with References given below for easily searching..
The document discusses dissolution as a tool in pharmaceutics. It defines dissolution as the process where a solid substance solubilizes in a solvent, transferring from the solid surface to the liquid phase. This is the rate-determining step for poorly soluble drugs. The document discusses three main mechanisms of dissolution - the diffusion layer model, Danckwert's model, and the interfacial barrier model. It also covers factors influencing dissolution such as drug properties, apparatus factors, and dissolution media properties. Finally, it provides details on three common dissolution apparatus - the basket, paddle, and reciprocating cylinder methods.
This document discusses various parameters used to characterize drug release from pharmaceutical formulations. It describes diffusion parameters defined by Higuchi's equation and plots. Dissolution parameters like the effects of agitation, pH, temperature, and medium properties are outlined. Pharmacokinetic parameters including Cmax, Tmax, and AUC are defined. The Heckel equation is presented as a method to analyze powder compaction. Similarity factors f1 and f2 are introduced to compare dissolution profiles. The Higuchi and Korsmeyer-Peppas models for drug release are presented.
The document discusses various methods to improve drug solubility including physical modifications like particle size reduction through micronization or formation of nanosuspensions, modification of crystal habit through polymorphism, and drug dispersion in carriers through techniques like solid dispersions. It also discusses chemical modifications such as changing pH, use of buffers, and derivatization. Other methods covered are complexation, solubilization by surfactants to form microemulsions, co-crystallization, cosolvency, hydrotrophy, and solvent deposition. The biopharmaceutical classification system relating solubility and permeability to drug absorption is also summarized.
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.
The document discusses different methods of microencapsulation including air suspension, coacervation, multiorifice centrifugal process, spray drying, and pan coating. It provides details on the working mechanisms and variables that affect each process. Microencapsulation can be used to encapsulate solids, liquids, or gases to properties such as shelf life, taste, and controlled release profiles.
DISSOLUTION AND FACTORS AFFECTING DISSOLUTIONDiksha Tapsale
Dissolution testing is used to determine how quickly an active ingredient is released from its solid dosage form into solution. There are many factors that can affect the dissolution rate, including properties of the drug substance, formulation excipients, processing methods, test apparatus parameters, and test conditions. Some key factors are the drug's particle size, solubility, solid state, salt form, excipient types and amounts, compression force, storage conditions, apparatus design features, stirring rate, temperature, and dissolution medium properties such as pH and viscosity. Careful control and standardization of these factors is important for obtaining reproducible dissolution test results.
This document discusses dissolution, which refers to the process by which a solid drug product dissolves into solution. It describes the film theory of dissolution, where a saturated film forms at the solid-liquid interface and drug diffusion through this film is the rate-determining step. Factors that affect dissolution are also outlined, including drug properties like solubility and particle size, as well as dosage form properties and test parameters. Equations for describing dissolution kinetics like the Noyes-Whitney and Hixson-Crowell cube root models are provided. Intrinsic dissolution rate, which measures dissolution under standardized conditions, is also defined.
The document provides an overview of pre-formulation, which involves determining the physicochemical properties of a drug substance prior to developing a dosage form. It discusses the goals of pre-formulation to formulate an efficacious dosage form with good bioavailability. The protocol involves characterizing the physical, chemical, solubility, stability and compatibility properties of the drug. Key aspects covered include polymorphism, hygroscopicity, particle size, solubility, dissolution, stability in solution and solid state, and compatibility with excipients. The information guides subsequent formulation development.
Phase solubility analysis and pH solubility profileMohit Angolkar
A Brief presentation on the topic- phase solubility analysis and pH solubility profile, which covers the following aspects:
- Solubility introduction
- importance of solubility
- factors influencing solubility
- Phase solubility analysis introduction
- method of analysis
- purification technique
- introduction to pH solubility profile.
Dissolution by Dr. Neeraj Mishra professor pharmaceuticsNeeraj Mishra
The document discusses dissolution, which is the process by which a solid substance enters the solvent phase to form a solution. Dissolution is important for drug absorption from oral dosage forms and can be the rate-limiting step. Dissolution testing is used for quality control, formulation development, and correlating in vitro dissolution to in vivo bioavailability. Theories of dissolution include diffusion layer models and surface renewal models. Factors that affect dissolution include drug properties, dosage form factors, particle size, polymorphism, salt formation, and lipid solubility.
This document discusses solubility and various techniques to improve drug solubility. It defines solubility and solubilization. It notes that drug effectiveness depends on solubility and bioavailability. It then describes techniques like spray freezing into liquid, ultra-rapid freezing, kneading, co-precipitation, and use of solubilizing agents to improve drug solubility. These techniques are aimed at developing drugs with improved solubility and permeability.
This document discusses solubility of drugs from the perspectives of a medicinal chemist and pharmaceutical scientist. From the medicinal chemist perspective, it discusses Lipinski's rule of five for predicting solubility and permeability. It also discusses methods for calculating absorption parameters and predicting aqueous solubility, such as the Moriguchi method for calculating logP. From the pharmaceutical scientist perspective, it outlines various techniques for enhancing drug solubility, including particle size reduction through micronization or nanosuspension, modifying crystal habit through polymorphs or complexes, and chemical modifications through prodrugs or buffer systems. Overall, the document provides an overview of key considerations and approaches for optimizing drug solubility from different scientific viewpoints.
ROLE OF DOSAGE FORM IN GASTRO-INTESTINAL ABSORPTION Ankit Malik
The document discusses how the dosage form impacts drug absorption in the gastrointestinal tract. It summarizes that solutions show the fastest and most complete absorption as they do not have dissolution problems. Suspensions also absorb relatively quickly due to their small particle size. Capsules and tablets must undergo dissolution and disintegration processes first. Coated tablets have an additional step of the coating dissolving or disrupting before drug absorption can occur. The dosage form selection can make over a 60-fold difference in a drug's absorption rate or extent.
The document provides an overview of drug dissolution including:
- Definitions of dissolution rate and intrinsic dissolution rate.
- Theories of drug dissolution including the diffusion layer model, Danckwert's model, and the interfacial barrier model.
- Factors that affect drug dissolution related to the physicochemical properties of drugs, drug product formulation, processing factors, dissolution apparatus and test parameters.
- Importance and applications of drug dissolution testing in product development, quality assurance, stability assessment, and biowaivers.
Formulation factors affecting drug absorptionshikha singh
This presentation discusses formulation factors that affect drug absorption. It identifies manufacturing variables like compression force during tablet production and granulation methods. It also discusses the influence of pharmaceutical ingredients like excipients, vehicles, diluents, and surfactants. Finally, it examines how the nature and type of the dosage form, such as solutions, suspensions, capsules and tablets, can impact drug absorption. The goal is to understand these formulation factors to develop dosage forms that allow drugs to be effectively absorbed and exert their pharmacological effects.
This presentation provides an detailed information about dissolution study. Furthermore, it provides various dissolution theories, application , various dissolution apparatus etc.
Dissolution parameters of a dosage formMOHAMMAD ASIM
Dissolution parameters include the effect of agitation, dissolution fluid, pH, surface tension, viscosity, additives, medium volume, deaeration, and temperature. Dissolution is the process where a solid dissolves into a liquid solvent via mass transfer. Key factors that influence dissolution rates include the pH and properties of the dissolution medium, agitation level, drug properties, and ensuring sink conditions. Maintaining proper test conditions such as temperature, medium volume, and sink conditions is important for obtaining reproducible and discriminating results.
This document discusses drug dissolution, which is the process by which a solid drug solubilizes in a solvent. It defines dissolution rate and describes the steps involved in drug release from tablets. Theories of dissolution including diffusion layer theory, Danckwert's model, and interfacial barrier theory are covered. Factors that affect dissolution such as drug properties, dosage form characteristics, and patient factors are also discussed. Common apparatus and methods used for conducting dissolution tests are presented. The document concludes that in vitro dissolution testing can help ensure batch-to-batch consistency and predict in vivo bioavailability.
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.
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.
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.
Physico-chemical factors affecting drug absorption from the gastrointestinal tract include particle size, crystal form, solubility, and pH partitioning. Smaller particle sizes increase surface area and dissolution rate, improving absorption for poorly soluble drugs. Different crystal forms of the same drug can have differing dissolution rates and absorption. Drugs must be in solution prior to absorption, so factors influencing solubility such as pH, salts, and complexation also impact absorption. The pH partitioning theory explains how a drug's ionization state influences its absorption, based on both its pKa and the pH of absorption sites. Dosage form characteristics such as solution versus tablet can also significantly affect drug absorption rates.
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.
includes different mechanism involved in the absorption of the drug s into the systemic circulation. different factors affecting absorption including characters of drugs and different dosage forms. bioavailability of different dosage forms
Solubility of poorly soluble drugs by using solid pptjagadeesh kumar
Three sentence summary:
Solid dispersion techniques can be used to improve the solubility and bioavailability of poorly soluble drugs. Various methods can be used to prepare solid dispersions, including solvent evaporation, melting, and spray drying. Characterization of the solid dispersions is important and can be done using methods like thermal analysis, spectroscopy, and dissolution testing to understand the physical properties and drug release behavior.
The document summarizes factors affecting drug absorption including pharmaceutical factors like drug properties and formulation factors. Some key points:
1. Drug solubility and dissolution rate are important factors, as the drug needs to be in solution for absorption. Hydrophobic drugs' absorption is limited by dissolution rate while hydrophilic drugs' absorption is limited by permeation rate.
2. Particle size reduction can increase surface area and dissolution rate, improving absorption, though this is not always recommended due to stability or irritation issues.
3. Polymorphism, hydration, and use of salt forms can impact solubility and dissolution rates compared to other forms of the same drug.
Factors bioavailability by d hi man saabMANISH KUMAR
This document discusses factors affecting the bioavailability of drugs. It states that biopharmaceutics studies the physicochemical properties of drugs and their bioavailability in vivo. The key factors discussed are those influencing dissolution and absorption. Dissolution must occur before absorption and is influenced by properties like surface area, particle size, crystal structure, and solubility. Absorption depends on factors like pH, lipid solubility, and molecular size. Overall, the document outlines important physicochemical characteristics of drugs that determine their bioavailability after administration.
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.
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.
Liquisolid technique is a new
and promising method that can change the dissolution rate of drugs. It has been used to enhance
dissolution rate of poorly water-soluble drugs.
Orally Disintegrating Tablets (ODT) which disintegrates rapidly in saliva, usually within seconds,
without need for water. Drug dissolution, absorption, the onset of action and drug bioavailability
may be significantly increased better than those obtained from conventional dosage forms. combination of this two techniques is a promising approach for effective drug delivery
This document discusses drug dissolution, including definitions, theories, mechanisms, factors affecting dissolution, intrinsic dissolution rate, and in-vitro dissolution testing models. It defines dissolution as the mass transfer of a solid substance into a liquid solvent. The key theories discussed are the diffusion layer model, Danckwert's penetration model, and the interfacial barrier model. Factors affecting dissolution include properties of the drug, test conditions, and dosage form characteristics. Common in-vitro dissolution testing models described are non-sink and sink methods that utilize natural or forced convection with varying degrees of agitation.
Formulation and Evaluation of Liquisolid Compacts of CarvedilolIOSR Journals
The purpose of this study is to develop a novel liquisolid technique to enhance the dissolution rate of
poorly water soluble drug Carvedilol, a BCS class II drug, which is a β-blocker, by using different excipients.
The main components of a liquisolid system are a non volatile solvent, carrier and coating materials and a
disintegrant. Liquisolid system refers to the formulations that are formed by conversion of liquid drugs, drug
suspensions or drug solution in non-volatile solvents into dry, non adherent, free flowing and compressible
powder mixture by blending with suitable carrier and coating materials. Hence the dissolution step, a prerequisite
for drug absorption, is by passed and better bioavailability of poorly soluble drug is achieved.
Liquisolid tablets of carvedilol are prepared by using PEG, PG, glycerine as non volatile liquid vehicles and
Avicel PH 101 and 102, Aerosil as carrier and coating materials respectively. Optimized formulation containing
20% drug in PEG 400, with Avicel 101 as carrier and Aerosil as coating material has shown 98.4% drug
release within 20 min which is better than marketed product (CARCA 12.5mg, Intas). The DSC and X-RD
studies are performed to investigate the physicochemical properties of formulation and drug excipient
interactions. The results are found to be satisfactory
This document discusses various parameters used to characterize drug release from pharmaceutical formulations, including diffusion parameters described by Higuchi's equation, dissolution parameters like the effects of agitation and pH, and pharmacokinetic parameters like Cmax, Tmax, and AUC. It also covers models like the Heckel equation that can be applied to understand powder compaction and the Korsmeyer-Peppas model for characterizing drug release mechanisms.
This document discusses optimization techniques used in pharmaceutical development. It defines optimization as choosing the best alternative from available options to make something as perfect or effective as possible. It discusses various optimization parameters like problem type (constrained vs unconstrained), variables (independent vs dependent), and methods like response surface methodology, factorial designs, evolutionary operations, and search methods. Response surface methodology uses statistical experimental designs like central composite designs to determine the relationship between independent and dependent variables and find the optimum formulation.
The document discusses ethics in computing in pharmaceutical research and computer use in market analysis. It addresses key ethical issues like privacy, liability, ownership, and power related to use of computers. It also discusses relevant codes of conduct for computer use and how computers can be used in market analysis to facilitate collection and dissemination of market information. A survey was conducted of industry participants to assess potential acceptance of computer-aided marketing systems. The advisory committee concluded such a system should be developed to complement existing marketing practices.
Quality by Design (QbD) is a systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding based on sound science and quality risk management. Key aspects of QbD include establishing a Quality Target Product Profile (QTPP) that identifies critical quality attributes (CQAs), understanding critical material attributes (CMAs) and critical process parameters (CPPs), and implementing a control strategy for CQAs and CPPs. The ICH Q8 guideline introduced QbD, and it has been further developed through guidelines like ICH Q9 and Q10. Examples show how QbD has been applied scientifically in different pharmaceutical development and manufacturing processes.
This document discusses the application of computer-aided techniques in developing pharmaceutical emulsions and microemulsions. It provides several examples of how experimental design and artificial neural networks have been used to optimize emulsion formulations and processing parameters. Specifically, researchers have used factorial design, response surface methodology, and artificial neural networks to determine the ideal concentrations of formulation components, processing conditions, and emulsifier mixtures to produce emulsions with desirable properties like stability, viscosity, and particle size. These computer-aided approaches allow for simultaneous optimization of multiple formulation parameters and provide a way to shorten product development time compared to traditional trial-and-error methods.
This document provides an overview of parenterals (injectable drugs). It discusses:
- Definitions and routes of administration including subcutaneous, intramuscular, intravenous, and others
- Formulation components like vehicles, buffers, antioxidants, and preservatives
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1. Factor Affecting GI Absorption of
a Drug
Presented By
KAHNU CHARAN PANIGRAHI
Asst. Professor in Pharmaceutics
12/14/2021
Factor affecting drug absorption by K.C
Panigrahi
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2. CONTENT
PHARMACEUTICAL FACTOR
A. Physiochemical Factor
• Drug solubility and dissolution rate
• Particle size and effective surface area
• Polymorphism, amorphism and Pseudopolymorphism
• Salt form of the drug
• pH partition hypothesis
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3. B. Pharmaco-techanical factor
• Disintegration time (tablets / capsules)
• Manufacturing variables
• Pharmaceutical ingredients (excipients / adjutants)
• Nature and type of dosage form
• Product age and storage conditions
PATIENT-RELATED FACTOR
• Age
• Gastric emptying time
• Intestinal transit time
• Gastro intestinal pH
• Disease status
• Blood flow through GIT
• Gastrointestinal content
• Pre-systemic metabolism
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4. Drug Solubility and Dissolution Rate
RDS RDS
for lipophilic drug for hydrophilic drug
Lipophilic Drug- Grisofulvin, Spirnolactone
Hydrophilic Drug- Neomycin, Cromolyn sodium
Maxmium absorbable dose(MAD) = Ka SGI VGI tr
Ka = intersic absobtion rate
SGI= solubility of drug in GI
VGI = volume of GI fluid
tr = residence time
If clinical dose < MAD , then absorption is not a limiting factor
Solid
drug
Solid
drug
particle
Drug in solution
at absorption
site
Permiation
Drug in
body
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5. Based on the intestinal permeability and solubility of drug,
Amidon et al. developed BCS.
Biopharmaceutical classification system
Class Solubility Permeability Absorption RDS step Example
1 High High High Gastric
emptying
Diltiazem
2 Low High Variable Dissolution Nifidipine
3 High Low Variable Permeability Insulin
4 Low Low Poor Case by case Taxol
Absolute intrinsic solubility: Maximum amount of solute dissolved in a given
solvent.
Dissolution rate: Amount solid substance that goes into solution per unit time
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6. Theories of drug dissolution
1.Diffusion layer model/Film theory
2.Danckwert model/Surface renewal theory
3.Interfacial barrier model/Limited solvation theory
1.Diffusion layer model/Film theory
• Solution of drug form a thin layer at solid liquid inter
face called as stagnant film or diffusion layer-rapid
step.
• Diffusion of soluble solute from stagnant layer to the
bulk solution-slow step or RDS step.
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8. From Noyes-Whitney’s equation of dissolution:
where,
D = diffusion coefficient or diffusivity of the drug molecule
A = surface area of the dissolving solid exposed to the
dissolution medium
KW/o = water/oil partition coefficient of the drug
V = volume of dissolution medium
h = thickness of the stagnant layer
Cs – CB = concentration gradient of the diffusing drug molecule.
dC
dt
DAK C C
Vh
W O S B
/ ( )
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• The previous equation shows a first order equation, the driving
force is concentration gradient i.e. Cs-Cb
• In vitro dissolution is in non-sink condition, and slow down after
some time .
• The in-vivo dissolution is rapid than in vitro dissolution as sink
conditions are maintained by absorption of drug in systemic
circulation i.e. Cb=0
• Thus in vivo no concentration build up occur in bulk solution
i.e. Cs >> Cb and sink condition maintained
• Under sink conditions, if the volume and surface area of the
solid are kept constant, then equation reduces to
dC/dt = K
• This represents that the dissolution rate is constant under sink
conditions and follows zero order kinetics i.e. yields a linear plot.
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To obtain good in vitro-in vivo dissolution rate correlation, the in
vitro dissolution must always be performed under sink conditions.
The in vitro sink conditions are so maintained that Cb is always less
than 10% of Cs.
This can be achieved in one or more of the following ways;
1.Bathing the dissolving solid in fresh solvent from time to time.
2. Increasing the volume of dissolution fluid.
3. Removing the dissolved drug by partitioning it from the aqueous
phase of the dissolution fluid into an organic phase placed either
above or below the dissolution fluid. Ex: hexane or chloroform.
4. Adding a water miscible solvent such as alcohol to the dissolution
fluid.
5. Adding selected adsorbents to remove the dissolved drug.
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Hixson-Crowell’s cubic root law of dissolution takes into account the particle size
decrease and change in surface area;
W0
1/3 – W1/3 = Kt
Where;
W0 = original mass of the drug.
W = mass of drug remaining to dissolve at time t.
Kt = dissolution rate constant.
12. 2.Danckwert model/Surface renewal theory
Non existence of stagnant layer
Trubulence in the dissolution media exist at interface
Danckwert takes into account the eddies or packets that are
present in the agitated fluid which reach the solid-liquid
interface, absorb the solute by diffusion and carry it into the
bulk of solution
Solute containing packets are continuously replaced with new
packet of fresh solvent
The Danckwert’s model is expressed by the equation;
Where;
• m = mass of solid dissolved.
• Gamma (γ) = rate of surface renewal.
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13. 3.Interfacial barrier model/Limited solvation theory
Intermediate concentration can exist at the interface as a result of solvation
mechanism and is a function of solubility rather then diffusion
G = Ki (Cs-Cb )
G= dissolution rate per unit area
Ki=effective interfacial transport constant
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14. PARTICLE SIZE AND EFFECTIVE SURFACE AREA
• Particle size and surface area of solid drug are inversely related to
each other.
• Absolute surface area: total area of solid particle, effective surface
area: area of solid surface exposed to dissolution medium
• According to Noyes-Whitney’s equation dissolution of drug
increases with increase in effective surface area
• For hydrophobic drug like griseofluvin,chloramphnicol increase of
effective surface area by micronisation result increase in
absorption.
• For hydrophobic surface drug like aspirin ,phenacetin the effective
surface area decreased by micronisation due to
1. Adsorption of air which inhibit wettability.
2. Reaggregation to form large particle due to high surface free
energy.
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The absolute surface area is converted to effective surface area by
I. use of surfactant which promote wettability eg-polysorbate-80
II. Adding hydrophilic diluent such as PEG,PVP
The effects of particle size on the absorption of phenacetin in man
16. POLYMORPHISIM, AMORPHISM AND PSEUDOPOLYMORPHISIM
INTERNAL STRUCTURE OF COMPOUND
CRYSTALINE
POLYMORPH
ENANTIOTROPIC MONOTROPIC
MOLECULAR ADUCT
STOICHIOMETRIC
(PSEUDOPOLYMORPHISM)
ORGANIC SOLVATE HYDRATES
NONSTOCHIOMETRIC
AMORPHOUS
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17. • When a substance exist in more than one crystalline from, the different form are designated as
polymorph and the phenomenon as polymorphism.
• Two type: Enantiotropic: reversibly changed into one another
Monotropic: unstable at all temperature and pressure
• Each polymorph are differ in their physical properties like solubility, melting point, density,
hardness, compression etc.
• These can be identified by optical crystallography, XRD, DSC etc.
• Increasing order of energy state and melting point
AMORPHOUS < METASTBLE < STABLE
• Increasing order of solubility
STABLE < METASTBLE <AMORPHOUS
• Example: Polymorphic form-III (metastable) of riboflavin is 20 times more water soluble than
the form-I (stable).
Novobiocin amorphous form 10 time more soluble then crystalline form.
• Conversion of metastable form to stable form can be inhibited by using thickening agent like
PVP, CMC, pectin, gelatin etc.
12/14/2021 Factor affecting drug absorption by K.C Panigrahi 17
18. The crystalline form may be either polymorph or molecular adduct.
The stoichimetric type of adduct where the solvent molecules are incorporated
in the crystal lattice which are call as solvates and the solvent as solvent of
crystallisation.
The solvates exist in different crystalline form are called as
pseudopolymorphism.
When the solvent associated is water then solvate are called as hydrate.
Generally anhydrous form has grater water solubility than the hydrates and
organic solvates have better aqueous solubility than anhydrous form.
e.g: The anhydrous form of ampicillin have higher aqueous solubility then
hydrous form but chloroform solvate of griseofluvin have more aqueous
solubility than non-solvate form.
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SALT FORM OF DRUG
• Most drug are either weak acid or weak base, hence these are
converted to their respective salt for in order to improve the
dissolution rate.
• Weakly acidic drug- a strong base salt is prepared e.g-sodium salt
of barbiturate and sulphonamide
• Weakly basic drug-a strong acid salt is prepared e.g-hydrochloride
of alkaloid
20. • For salt of weak acid (p H)d > (p H)b which favor
solubility of free acid similarly for salt of weak base(p
H)d < (p H)b which favor solubility of free base. (d-
diffusion layer, b- bulk of solution)
• The decrease in p H of the diffusion layer is due to
buffer action of strong base cation or strong acid anion.
• Precipitation of free acid occur when diffuses into
acidic medium having less solubility. These are fine
particle having large surface area leads increase
solubility.
Example: Aspirin, Penicillin etc.
• Smaller the size of counter ion greater the solubility
e.g-Ratio of solubility of novobiocin of its sodium salt ,
calcium salt , free acid is 50:25:1
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21. p H PARTITION HYPOTHESIS-
The theory states that For drug compound of molecular
weight grater than 100, which are transported by passive
diffusion, the process of absorption governed by.
• The dissociation constant (pKa) of drug.
• The lipid solubility of unionized drug (K o/w).
• The pH of absorption site.
On simplifying above theory-
• If the p H on either side of the compartment is different
than the compartment whose p H favor ionization of drug
contain grater amount of drug.
• Only unionized drug with sufficient lipophilicity can
permeate the membrane passively.
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22. The above statement of theory based on assumption that-
1. GIT is a simple lipoidal barrier for transport of drug
2. Larger the fraction of unionized drug faster the absorption
3. Greater the lipophilicity greater the absorption
Drug pKa and GI pH
The amount of drug that exists in unionized form is a function of
dissociation constant (pKa) of the drug and pH of the fluid at the
absorption site. By applying Henderson-Hesslback equation :
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23. Considering p H of GIT in between 1-8. 1-3: stomach, 5-8: intestine
CATEGORY DRUG pKa SITE OF ABSORPTION
Very weak acid Phenobarbital >8 Entire GIT
Phenytoin
Moderately weak Ibuprofen 2.5-7.5 STOMACH
Cloxacillin
Strong acid Disodium
cromoglycate
<2.5 Poorly absorbed
Very weak base Thophylline <5 Entire GIT
Dizepam
Moderately weak Reserpine 5-11 INTESTIN
Codeine
Strong base Mecamylamine >11 Poorly absorbed
guanethidine
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24. o For optimum absorption, a drug ideally should have
sufficient aqueous solubility and lipid solubility high
enough to facilitate partitioning of drug in lipoidal
membrane
o So there should be a perfect HLB for optimum
bioavailability
o A P value of range 1-2 sufficient for passive absorption.
P: Partition coefficient
o P value calculated considering octanol /p H 7.4 buffer
Rapid rate absorption Moderate rate Slow rate
Phenylbutazone Aspirin Barbituric acid
thiopental Theophylline sulphaguanidne
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25. LIMITATION :
1.Presence of virtual membrane p H
An S shaped curve, called the p H absorption
curve denoting dissociation of drug
For acidic drug – shift to right basic drug-shift
to left
Suggest a microclimate p H different from the
luminal p H which is called virtual membrane p
H
2.Absorption of ionised drug
Principle of non ionic diffusion-ionised drug
absorption 3-4 time less then non ionised
Some drug having large lipophilic group(e.g-
morphin) despite of their ionisation absorbe
passively
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26. 3.Influence of GI surface area and residence
time of drug
According to PH partition hypothesis acidic
drug best absorbed from stomach while
basic drug absorbed from intestine
But due to large surface area of lumen and
longer residence time of drug in intestine
both acidic and basic drug absorbed
predominantly
4.Presence of aqueous unstirred diffusion layer
The shift of p H absorption curve suggest
that the drug is not directly in contact with
the membrane, but a barrier called as
aqueous unstirred diffusion layer present in
between them.
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27. RULE 5 :lipinski
molecular weight < 500
Lipophilicity logP < 5
Number of H-bond acceptor < 10
Number of H-bond donor < 5
Any of the above 2 more then the
specified value then absorption may be
significant problem
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28. B. Pharmaco-techanical factor
1.Disintegration time
Depend on coating, amount of binder
2. Manufacturing variables
Method of granulation-wet granulation, direct
compression, agglomerative phase communition
Compression force-in four way
3. Product age and storage conditions
Alter solubility due to conversion of metastble form to
stable form or change in particle size distribution in case of
suspension, increase in excipient hardness e.g - PVP, acacia
and decrees in hardness for binder like CMC
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29. 4.Effect of Excipients on the Pharmacokinetic
1. Vehicle
2. Diluent
3. Binder
4. Disintegrant
5. Lubricant
6. Coating
7. Suspending agent
8. Surfactants
9. Complexing agents
10.Buffers
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30. Parameters of Oral Drug Products
Excipients Example k a T MAX AUC
Disintegrants Avicel, Explotab + - +/0
Lubricants Talc, hydrogenated
vegetable oil
- + -/0
Coating agent Hydroxypropylmethyl
cellulose
0 0 0
Enteric coat Cellulose acetate phthalate - + -/0
Sustained-release
agents
Methylcellulose,
ethylcellulose
- + -/0
Sustained-release
agents (waxy agents)
Castorwax, Carbowax - + -/0
Sustained-release
agents (gum/viscous)
Veegum, Keltrol - + -/0
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31. 5.Nature and type of dosage form
Slowest
A
B
S
O
R
P
T
I
O
N
Fastest
TABLET
CAPSULE
POWDER
(COARSE)
SUSPENSION
EMULSION
SOLUTION
GRANULES
FINE PARTICLES
DRUG IN SOLUTION
DRUG IN BLOOD
Disintegration
Disoslution of capsule shell
Deaggregation
Dissolution
Absorption
Partition form oil
phase to aqueous phase
Biomembrane
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