Drug absorption from the gastrointestinal tractSUJITHA MARY
The document discusses drug absorption from the gastrointestinal tract (GIT). It describes the key mechanisms of drug absorption including passive diffusion, carrier-mediated transport, pore transport, ionic diffusion, and vesicular transport. Factors that affect drug absorption are also covered, such as physicochemical properties like drug solubility and dissolution rate, particle size, polymorphism/amorphism, salt form, and lipophilicity. Pharmaceutical factors and patient-related factors that influence absorption are also outlined. The document provides detailed explanations of the various mechanisms and factors involved in drug absorption from the GIT.
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.
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.
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.
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.
This document discusses techniques to enhance the solubility and dissolution rate of poorly soluble drugs. It begins with an overview of compaction profiles when forming tablets. The bulk of the document focuses on solubility enhancement techniques, including physical modifications like particle size reduction and solid dispersions, chemical modifications like changing pH and derivatization, and other methods like co-solvency. A variety of specific techniques are described within each category to improve a drug's solubility such as micronization, nanosuspensions, cyclodextrin complexation, and use of surfactants, buffers, or co-solvents. The document provides details on the mechanisms and examples of various solubility enhancement methods.
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 process where a solid substance solubilizes in a solvent. The key theories of drug dissolution discussed are the diffusion layer model, Danckwert's model, and the interfacial barrier model. Factors that can impact dissolution include properties of the drug substance, dosage form excipients, test conditions, and more. Intrinsic dissolution rate is defined as the dissolution of pure substances under standardized conditions. Various in-vitro dissolution testing models are also summarized, including non-sink and sink methods.
Drug absorption from the gastrointestinal tractSUJITHA MARY
The document discusses drug absorption from the gastrointestinal tract (GIT). It describes the key mechanisms of drug absorption including passive diffusion, carrier-mediated transport, pore transport, ionic diffusion, and vesicular transport. Factors that affect drug absorption are also covered, such as physicochemical properties like drug solubility and dissolution rate, particle size, polymorphism/amorphism, salt form, and lipophilicity. Pharmaceutical factors and patient-related factors that influence absorption are also outlined. The document provides detailed explanations of the various mechanisms and factors involved in drug absorption from the GIT.
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.
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.
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.
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.
This document discusses techniques to enhance the solubility and dissolution rate of poorly soluble drugs. It begins with an overview of compaction profiles when forming tablets. The bulk of the document focuses on solubility enhancement techniques, including physical modifications like particle size reduction and solid dispersions, chemical modifications like changing pH and derivatization, and other methods like co-solvency. A variety of specific techniques are described within each category to improve a drug's solubility such as micronization, nanosuspensions, cyclodextrin complexation, and use of surfactants, buffers, or co-solvents. The document provides details on the mechanisms and examples of various solubility enhancement methods.
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 process where a solid substance solubilizes in a solvent. The key theories of drug dissolution discussed are the diffusion layer model, Danckwert's model, and the interfacial barrier model. Factors that can impact dissolution include properties of the drug substance, dosage form excipients, test conditions, and more. Intrinsic dissolution rate is defined as the dissolution of pure substances under standardized conditions. Various in-vitro dissolution testing models are also summarized, including non-sink and sink methods.
This document discusses pharmacokinetics and specifically the absorption process. It defines absorption as the movement of a drug from its site of administration into the bloodstream. The four main processes involved in pharmacokinetics - absorption, distribution, metabolism, and elimination (ADME) - are initially outlined. Several mechanisms of drug absorption in the gastrointestinal tract are then described in detail, including passive diffusion, carrier-mediated transport, phagocytosis, and others. Factors that can influence drug absorption and bioavailability are also summarized, such as pharmaceutical factors like drug solubility and formulation, as well as pharmacological factors like gastric emptying time.
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.
mehods to enhance the solubility of poorly soluble drugsPraveenHalagali
Mr. Praveen Halagali presented on different techniques to enhance drug solubility to Dr. D.V. Gowda. The presentation covered the importance of solubility for drug bioavailability and listed various physical, chemical, and technological methods to improve solubility. These included reducing particle size, modifying crystal forms, complexation, and use of surfactants, cosolvents, and nanotechnology approaches like nanocrystals and nanomorphs. The mechanisms and specific techniques involved in each method were described in detail.
The document discusses dissolution testing of pharmaceutical solid dosage forms. It defines dissolution as the amount of drug substance that goes into solution per unit time under standardized conditions. Dissolution testing is important for quality control to ensure uniform drug release and bioavailability. The key mechanisms of dissolution are the diffusion layer model, Danckwert's model, and the interfacial barrier model. Factors that influence dissolution include apparatus parameters, drug properties, and dosage form composition. Common apparatus are the basket, paddle, and flow-through cell methods. Acceptance criteria and methods to enhance dissolution through nanonization or changes to formulation are also covered.
PHYSICOCHEMICAL FACTORS AFFECTING DRUG ABSORPTIONAffrin Shaik
This document discusses the physicochemical and pharmaceutical factors that affect drug absorption after oral administration. It outlines 8 physicochemical factors including drug solubility, particle size, polymorphism, salt form, lipophilicity, and stability. It also discusses how the pH of the gastrointestinal tract relates to a drug's pKa according to the pH-partition hypothesis. The document then briefly outlines pharmaceutical factors like dosage form and patient-related factors that can also influence drug absorption.
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.
Factors Affecting Drug Absorption {BRD}.pptxGirijaSoori
1) The document discusses factors that affect drug absorption from solid oral dosage forms like tablets and capsules. Key factors discussed include dissolution rate, disintegration time, manufacturing processes, excipients, and physicochemical properties of the drug.
2) Excipients like binders, lubricants, and coatings can impact drug absorption by affecting properties like hardness, porosity, and wettability which influence dissolution. Hydrophilic excipients generally promote dissolution while hydrophobic ones can inhibit it.
3) Physicochemical properties of the drug such as solubility, particle size, and solid state also significantly impact dissolution rate and therefore absorption. Increasing solubility through salt formation or reducing particle size can enhance absorption.
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.
Dissolution apparatus, invivo-invitro corelation, factor affecting,BCS classification ..
Complete dissolution topic in this slide & easy way to write..
Cheak it now and give feedback
Physicochemical Properties effect on Absorption of DrugsSuraj Choudhary
This document discusses factors affecting drug absorption from oral dosage forms. It covers physiological factors like gastric emptying time and pH, as well as physicochemical drug properties including solubility, dissolution rate, and polymorphism that influence drug absorption. Particle size and surface area are emphasized, with smaller particles increasing absorption for hydrophilic drugs but potentially decreasing it for hydrophobic drugs. The pH partition hypothesis and importance of drug stability are also summarized.
This document summarizes factors that affect drug absorption including pharmaceutical factors like drug solubility, particle size, polymorphism, and formulation factors as well as patient-related factors like gastric emptying time, gastrointestinal pH, and disease states. Some key pharmaceutical factors discussed are how smaller particle size increases surface area and dissolution rate, amorphous forms have higher solubility than crystalline forms, and solubility of different polymorphs and hydrates can impact absorption. The summary briefly outlines several formulation excipients and how they may influence drug absorption.
This document discusses various methods for enhancing the solubility of poorly soluble drugs, which is important for improving their bioavailability. It describes solubility and defines it qualitatively and quantitatively. It then explains the need for and categories of solubility enhancement techniques, including physical modifications, chemical modifications, and miscellaneous methods. Some key physical modification techniques discussed are particle size reduction through micronization and nanosuspensions, modifying the crystal habit through polymorphism, and using drug carriers like solid dispersions and cryogenic techniques. Chemical modification techniques include changing the pH, complexation, salt formation, and neutralization. Miscellaneous methods include microemulsions, use of adjuvants like surfactants, and cosolvency.
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.
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.
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.
The document discusses various techniques for enhancing the solubility of poorly soluble drugs. It begins by explaining the importance of drug solubility for bioavailability and effectiveness. The main techniques discussed include reducing particle size through methods like micronization and nanosuspensions. It also covers modifying the crystal structure of drugs through polymorphism, amorphism, and changing hydration states. The document provides details on methods like sonocrystallization and supercritical fluid processing for size reduction.
This document discusses pharmacokinetics and specifically the absorption process. It defines absorption as the movement of a drug from its site of administration into the bloodstream. The four main processes involved in pharmacokinetics - absorption, distribution, metabolism, and elimination (ADME) - are initially outlined. Several mechanisms of drug absorption in the gastrointestinal tract are then described in detail, including passive diffusion, carrier-mediated transport, phagocytosis, and others. Factors that can influence drug absorption and bioavailability are also summarized, such as pharmaceutical factors like drug solubility and formulation, as well as pharmacological factors like gastric emptying time.
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.
mehods to enhance the solubility of poorly soluble drugsPraveenHalagali
Mr. Praveen Halagali presented on different techniques to enhance drug solubility to Dr. D.V. Gowda. The presentation covered the importance of solubility for drug bioavailability and listed various physical, chemical, and technological methods to improve solubility. These included reducing particle size, modifying crystal forms, complexation, and use of surfactants, cosolvents, and nanotechnology approaches like nanocrystals and nanomorphs. The mechanisms and specific techniques involved in each method were described in detail.
The document discusses dissolution testing of pharmaceutical solid dosage forms. It defines dissolution as the amount of drug substance that goes into solution per unit time under standardized conditions. Dissolution testing is important for quality control to ensure uniform drug release and bioavailability. The key mechanisms of dissolution are the diffusion layer model, Danckwert's model, and the interfacial barrier model. Factors that influence dissolution include apparatus parameters, drug properties, and dosage form composition. Common apparatus are the basket, paddle, and flow-through cell methods. Acceptance criteria and methods to enhance dissolution through nanonization or changes to formulation are also covered.
PHYSICOCHEMICAL FACTORS AFFECTING DRUG ABSORPTIONAffrin Shaik
This document discusses the physicochemical and pharmaceutical factors that affect drug absorption after oral administration. It outlines 8 physicochemical factors including drug solubility, particle size, polymorphism, salt form, lipophilicity, and stability. It also discusses how the pH of the gastrointestinal tract relates to a drug's pKa according to the pH-partition hypothesis. The document then briefly outlines pharmaceutical factors like dosage form and patient-related factors that can also influence drug absorption.
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.
Factors Affecting Drug Absorption {BRD}.pptxGirijaSoori
1) The document discusses factors that affect drug absorption from solid oral dosage forms like tablets and capsules. Key factors discussed include dissolution rate, disintegration time, manufacturing processes, excipients, and physicochemical properties of the drug.
2) Excipients like binders, lubricants, and coatings can impact drug absorption by affecting properties like hardness, porosity, and wettability which influence dissolution. Hydrophilic excipients generally promote dissolution while hydrophobic ones can inhibit it.
3) Physicochemical properties of the drug such as solubility, particle size, and solid state also significantly impact dissolution rate and therefore absorption. Increasing solubility through salt formation or reducing particle size can enhance absorption.
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.
Dissolution apparatus, invivo-invitro corelation, factor affecting,BCS classification ..
Complete dissolution topic in this slide & easy way to write..
Cheak it now and give feedback
Physicochemical Properties effect on Absorption of DrugsSuraj Choudhary
This document discusses factors affecting drug absorption from oral dosage forms. It covers physiological factors like gastric emptying time and pH, as well as physicochemical drug properties including solubility, dissolution rate, and polymorphism that influence drug absorption. Particle size and surface area are emphasized, with smaller particles increasing absorption for hydrophilic drugs but potentially decreasing it for hydrophobic drugs. The pH partition hypothesis and importance of drug stability are also summarized.
This document summarizes factors that affect drug absorption including pharmaceutical factors like drug solubility, particle size, polymorphism, and formulation factors as well as patient-related factors like gastric emptying time, gastrointestinal pH, and disease states. Some key pharmaceutical factors discussed are how smaller particle size increases surface area and dissolution rate, amorphous forms have higher solubility than crystalline forms, and solubility of different polymorphs and hydrates can impact absorption. The summary briefly outlines several formulation excipients and how they may influence drug absorption.
This document discusses various methods for enhancing the solubility of poorly soluble drugs, which is important for improving their bioavailability. It describes solubility and defines it qualitatively and quantitatively. It then explains the need for and categories of solubility enhancement techniques, including physical modifications, chemical modifications, and miscellaneous methods. Some key physical modification techniques discussed are particle size reduction through micronization and nanosuspensions, modifying the crystal habit through polymorphism, and using drug carriers like solid dispersions and cryogenic techniques. Chemical modification techniques include changing the pH, complexation, salt formation, and neutralization. Miscellaneous methods include microemulsions, use of adjuvants like surfactants, and cosolvency.
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.
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.
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.
The document discusses various techniques for enhancing the solubility of poorly soluble drugs. It begins by explaining the importance of drug solubility for bioavailability and effectiveness. The main techniques discussed include reducing particle size through methods like micronization and nanosuspensions. It also covers modifying the crystal structure of drugs through polymorphism, amorphism, and changing hydration states. The document provides details on methods like sonocrystallization and supercritical fluid processing for size reduction.
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10. 1. Diffusion Layer Model
Also called ‘film theory’.
Formation of a thin film at the interface, called as stagnant
layer.
2 steps are involved:1) Interaction of solvent with drug
surface to form a saturated drug layer , called stagnant
layer.
2) Diffusion of drug molecules from stagnant layer into bulk
of the system.
10
12. Nernst and brunner incorporated Ficks first law of
diffusion and modified the equation Noyes and
Whitney equation to :
dc/dt = DAKw/o (Cs-Cb) / Vh
Where,
dC/dt = Dissolution rate of the drug,
12
13. D= Diffusion coefficient (diffusivity) of the drug
A= Surface area of the dissolving solids
13
14. Kw/o –water/oil partition coefficient of the drug
considering the fact that dissolution body fluids are
aqueous. Since the rapidity with which a drug
dissolves depends on the Kw/o.
V – volume of dissolution medium.
14
15. h – thickness of the stagnant layer(This film forms
a thin stagnant layer (h) around the particle. There
is a stagnant layer or diffusion layer which is
saturated with the drug more the thickness , lesser
the diffusion and drug dissolution, then the drug
reaches bulk solution)
Cs-Cb- concentration gradient for diffusion of drug.
15
16. 2.Particle Size & Effective Surface Area :
• Particles size plays a major role in drug absorption.
• Dissolution rate of solid particles is proportional to surface
area.
• Smaller particle size , greater surface area then higher will be
dissolution rate , because dissolution is thought to take place at
the surface area of the solute(drug).
• Particle size reduction has been used to increase the
absorption of a large number of poorly soluble drugs.
• E.g.Bishydroxycoumarin,digoxin .
17. • Two types of surface area
• 1) Absolute surface area : Is the total area of solid surface of
any particle.
• 2)Effective surface area: Is the area of solid surface exposed to
the dissolution medium.
• To increase the effective surface area, we have to reduce the
size of particle up to 0.1 micron. So these can be achieved by
“Micronisation process”.
18. • But in these case one most important thing to be keep in mind that which
type of drug is micronized it is :
• a) Hydrophilic b)Hydrophobic
• a)HYDROPHILIC DRUGS :
• In hydrophilic drugs the small particles have higher energy than the bulk
of the
• solid resulting in an increased interaction with the solvent.
• E.g. 1.Griesiofulvin – dose reduced to half due to micronisation.
• 2.Digoxin – the bioavailability was found to be 100% in micronized tablets.
• After micronisation it was found that the absorption efficiency was highly
• increased.
19. • b)HYDROPHOBIC DRUGS:
• In this micronisation techniqies result in decreased effective
surface area & thus fall in dissolution rate.
20.
21. 3.Polymorphism & amorphism:
• 3.Polymorphism & amorphism:
• Depending upon the internal structure , a sloid can exist either
in a crystalline or amorphous form.
• When a substance exist in more than one crystalline form, the
different forms are designated as polymorphs ,and the
phenomenon as polymorphism.
22. • Polymorphs are of two types :
• 1.Enantiotropic polymorph is the one which can be reversibly
changed into another form by altering the temp or pressure.
E.g. Sulphur.
• 2.Monotropic polymorph is the one which is unstable at all the
temp & pressure. E.g. glyceryl stearates.
23. • The polymorphs differ from each other with respect to their
physical properties such as solubility , melting point, density,
hardness and compression characteristics .
• Thus , these change in physical properties and hence the
• absorption.
24. • AMORPHISM : some drugs can exist in amorphous form
(i.e.having no internal crystal structure). Such drugs represent
the highest energy states.
• They have greater aqueous solubility than the crystalline form
because a energy required to transfer a molecule from the
crystal lattice(is the arrangement of atoms, molecules, or ions of
a crystal in the form of a space lattice) is greater than that
required for non-crystalline.
25. 4.Pseudopolymorphism(Hydrates/solv
ates)
• SOLVATES:
• The stoichiometric type of adducts where the solvent molecules
are incorporated in the crystal lattice of the solid are called as
the solvates , and the trapped solvent as solvent of
crystallization .
• The solvates can exist in different crystalline forms called as
pseudopolymorphs.
26. • HYDRATES: when the solvent in association with the drugs is
water , the solvates in known as a hydrates.
• Hydrate are pseudo-polymorphs where hydrates are less
soluble and solvent are more soluble and thus affect the
absorption accordingly.
27. • The anhydrous form of a drug has greater aqueous solubility
than the hydrates.
• The anhydrous form of theophylline and ampicillin have higher
aqueous solubilities, dissolves faster rate and show better
bioavailability.
• In comparison to their monohydrate and trihydrate forms.
28.
29. 5.Salt form of the drug:
• Example of salt of weak acid : It increases the pH of the
diffusion layer , which promotes the solubility the dissolution of
a weak acid and absorption is bound to be rapid.
30.
31.
32.
33.
34.
35.
36. 8.Drug Stability:
• A drug for oral use may destabilize either during its shelf life or in the
GIT.
• Two major stability problems resulting in poor bioavailability of an
orally administered drug are degradation of the drug into inactive
form and interaction with one or more different component either of
the doage form or those present in the GIT to form a complex that is
poorly soluble or is unabsorbable.
37. B) PHARMACEUTICAL FACTORS:
• 1)Disintegration time :
• Rapid disintegration is important to have a rapid absorption so lower
disintegration time is required.
• Disintegration time of tablet is directly proportional to amount of
binder & compression force.
38. • In vitro disintegration test gives no means of a guarantee of drugs
bioavailability because if the disintegrated drug particles do not
dissolve then absorption is not possible.
• E.g.Coated Tablet : they have long disintegration time.
• Fast dispersible tablet have short disintegration time.
39. 2)Dissolution time:
• Dissolution is a process in which a solid substance solubilizes in a
given solvent
• i.e. mass transfer from the solid surface to the liquid phase.
• Dissolution time is also an important factor which affect the drug
absorption.
40. 3)Manufacturing variables:
• Several manufacturing processes influence drug dissolution from solid
dosage forms.
• E.g. For tablet its
• Method of granulation
• Compression force
41. • Wet granulation is the most conventional technique in the
manufacture of tablets that dissolve faster.
• The limitations include:
• The liquid may act as a medium for affecting chemical reactions such
as hydrolysis.
• The drying step may harm the thermolabile drugs.
42. • b) Compression force:
• Higher compression force yields a tablet with greater hardness
• and reduced wettability & hence have a long D.T.
• but on other hand higher compression force cause crushing of drug
particles into smaller ones with higher effective surface area which in
• decrease in D.T.
• So effect of compression force should be thoroughly studied on
• each formulation.
43. 4)Pharmaceutical ingredients:
• More the number of excipient in the dosage form, more
complex is & greater the potential for absorption and
bioavailability problems.
44. • a)Vehicles:
• Rate of absorption – depend on its miscibility with biological
fluid.
• The 3 categories:
• 1. Aqueous vehicle(water, syrup)
• 2.Non Aqueous water Miscible vehicles(propylene
glycol,glycerol,sorbitol)
• 3.Non Aqueous water immiscible vehicles(Vegetable oils)
• Aqueous and water miscible vehicles are miscible in the body
fluids and drugs from them are rapidly absorbed.
45. • A drug is more soluble in water Miscible vehicles causes rapid
absorption and shows better bioavailability e.g.propylene glycol.
• Immiscible vechicle – Absorption depend on its partitioning from oil
phase to aqueous body fluid.
46. • b)Diluent:
• Hydrophilic diluent – impact Absorption
• Hydrophobic diluent – Retards Absorption
• Also , there is a drug diluent interaction , forming
insoluble complex and retards the absorption.
• Widely used diluents example: Starch, lactose,
microcrystalline cellulose etc.
47. • Hydrophilic diluents-form the hydrophilic coat around
hydrophobic drug particles –thus promotes
dissolution and absorption of poorly soluble
hydrophobic drug.
• Dicalcium Phosphate(DCP) is most common inorganic
diluents.
• Interaction of tetracycline and DCP will form complex
which is poorly soluble and unabsorbable.
48. c)Binder & granulating agent :
• These materials are used to hold powders together to form granules
or promote cohesive compacts for directly compressible materials
and to ensure that the tablet remains intact after compression.
• E.g Starch, PVP etc,
49. • Hydrophilic binders – imparts hydrophilic properties to granule
• surface – better dissolution of poorly wettable drug. e.g. starch,
• gelatin, PVP.
• More amount of binder – increases hardness of tablet – decrease
dissolution & disintegration rate.
50. d)Disintegrants:
• Mostly hydrophilic in nature,
• Decrease in amount of disintegrant – significantly lowers
bioavailability.
• E.g Bentonite, microcrystalline cellulose etc.
51. e) Lubricants :
• These agents are added to tablet formulations to aid flow of granules,
to reduce interparticle friction and sticking or adhesion of particles to
dies and punches.
• E.g stearates and waxes.
52. • Commonly hydrophobic in nature – therefore inhibits penetration of
water into tablet and thus dissolution and disintegration.
• Can be prevented by adding the lubricants in the final stage.
53. f)Suspending agent :
• Stabilized the solid drug particles by reducing their rate of settling
through an increase in the viscosity of the medium and thus affect drug
• Absorption in several ways.
• Macromolecular gum forms unabsorbable complex with drug
• e.g. Na CMC.
• Viscosity imparters – act as a mechanical barrier to diffusion
• of drug from its dosage form and retard GI transit of drug.
54. g)Colorants:
• Even a low concentration of water soluble dye can have an
inhibitory effect on dissolution rate of several crystalline drugs.
• The dye molecules get absorbed onto the crystal faces and inhibit the
drug dissolution.
• e.g: Brilliant blue retards dissolution of sulfathiazole.
55. g)Complexing agent:
• Complex formation has been used to alter the
physicochemicals & biopharmaceutical proporties of a drug.
• E.g.
• 1.Enhanced dissolution through formation of a soluble complex.
E.g ergotamine tartarate- caffeine complex
• 2.Enhanced lipophilicity for better membrane permeability. E.g
caffine-PABA complex.
• 3. Enhanced membrane permeability E.g EDTA which chealates
calcium and magnesium ions of the membrane
56. h. Product age and storage conditions :
• Product aging and improper storage conditions adversely affect B.A.
• e.g: precipitation of drug in solution decrease rate of Change in
particle size of suspension drug dissolution & Hardening of tablet &
absorption.
57. C) PATIENT RELATED FACTOR:
• Gastric emptying: apart from the dissolution of drug and its
permeation through the bio membrane, the passage from stomach to
small intestine, called as gastric emptying,can also be a rate limiting
step in absorption because the major site of drug absorption is
intestine.
• It is advisable where:
• Rapid onset of drug is desired eg:sedatives
• Drug not stable in gastric fluids eg:pencillin G
• Dissolution occuring in intestine eg: enteric coated forms
58. • Delay in gastric emptying is recommended in particular
• where:
• Food promotes drug dissolution and absorption
• eg: griseofulvin.
• The drugs dissolve slowly.
• Disintegration and dissolution of dosage form is promoted by gastric
fluids.
59. • Gastric emptying is first order process. Several parameters used to
quantify are:
• Gastric emptying rate: speed at which stomach contents
• empties into intestine.
• Gastric emptying time: time required for gastric contents
• to empty into small intestine
• Gastric emptying t1/2 : time taken for half of the stomach
• contents to empty
60. 2)Intestinal transit time:
• Since small intestine is the major site for absorption of most
drugs, long intestinal transit time is desirable for complete drug
absorption.
• The mixing movement of the intestine that occurs due to
peristaltic contraction promotes drugs absorption,
• firstly by increasing the drug intestinal membrane contact and
• secondly by enhancing drug dissolution of especially of poorly
soluble drug through induced agitation.
61. • Delayed intestinal transit is desirable for
• 1.Drugs that dissolve or release slowly from their dosage form.
• 2.Drugs that dissolve only in intestine
• 3.Drug absorbed from specific sites in the intestine.
62. • Laxatives promote the rate of intestinal transit.
• Anticholinergic drugs: retard gastric and intestinal transit
• promote absorption of poorly soluble drugs eg:propantheline
• Intestinal transit time is influenced by various factors such as
food , diseases and drug.
63.
64.
65. Gastrointestinal diseases:
• Altered GI motility:
• They may not have adequate production of acid in the stomach ,
• stomach acid is essential for solubilizing insoluble free bases.
• Gastrointestinal diseases and infections:
• Two of the intestinal disorders related with malabsorption syndrome(the small
intestine can't absorb enough of certain nutrients and fluids) that influence drug
availability are celiac disease and Crohn’s disease.
• Crohn’s disease that can alter absorption pattern are altered gut wall microbial
flora, decreased gut surface area and intestinal transit rate.
• GI infections like shigellosis(intestinal disease caused by a family of bacteria
), gastroenteritis, cholera and food poisoning also result in malabsorption.
66. • Gastrointestinal surgery:
• Gastrectomy(surgical removal of a part or the whole of the stomach)
can result in drug dumping in the intestine, osmotic diarrhoea and
reduced intestinal transit time.
• Cardiovascular diseases:
• Decreased blood flow to the GIT and gastric emptying
• rate and altered GI pH, secretions and microbial flora.
• Several changes associated with congestive cardiac failure
• influence bioavailability of a drug.
67. • Hepatic diseases:
• Disorders such as hepatic cirrhosis(liver does not function properly
due to long-term damage) influence bioavailability mainly of drugs
that undergo considerable first-pass hepatic metabolism.
• e.g. propranolol.
68. 4)Blood flow through the GIT:
• maintain the concentration gradient across the epithelial
membrane.
• GIT is extensively supplied by blood capillary network.
• Blood flow is important for actively absorption of drugs.
• Absorption of polar molecules doesn’t depend on the blood
flow but lipid soluble molecules highly depend on the blood flow.
69. 5)GIT Content:
• A)Food –drug interactions: the presence of food in the GI
tract can affect the bioavailability of the drug.
• Digested foods contain amino acid , fatty acid and many
nutrient that may affect intestinal pH and solubility of drugs.
• Some effect of food on the bioavailability of a drugs from a
drug product include:
• Delay in gastric emptying , Stimulation of bile flow , A change in
the pH of the GI tract , An increase in splanchnic blood flow.
70.
71.
72.
73.
74. • B) Fluid volume:
• Large fluid volume result in better dissolution , rapid gastric
emptying and enhanced absorption. E.g Erythromycin is better
absorbed when taken with a glass of water fasting condition
than when taken with meals.
75. • C)Interaction of drug with normal GI constituents:
• The GIT contain a number of normal constituents such as
mucin which is a protective mucopolysaccharides that lies the
GI mucosa , interact with streptomycin.
76.
77. • A)Luminal Enzymes: the primary enzyme found in gastric juice
is pepsin . Lipases , amylases and proteases are secreted from
the pancreas into the small intestine in response to
ingestion(the process of taking food) of food.
• Pepsins and the proteases are responsible for the degradation
of protein and peptide drugs in the lumen.
78.
79. • Gut wall enzymes: also called as mucosal enzymes present in
• stomach, intestine and colon.
• Alcohol dehydrogenase: enzyme of stomach mucosa
• inactivates ethanol.