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.
Introduction
Mechanisms of protein drug binding
Kinetics of protein drug binding
Classes of protein drug binding.
1. Binding of drug to blood components.
(a) Plasma proteins
(b) Blood cells
2. Binding of drug to extravascular tissue protein
Determination of Protein-drug Binding
Factors affecting protein drug binding
Significance of protein/tissue binding of drug
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
Introduction
Mechanisms of protein drug binding
Kinetics of protein drug binding
Classes of protein drug binding.
1. Binding of drug to blood components.
(a) Plasma proteins
(b) Blood cells
2. Binding of drug to extravascular tissue protein
Determination of Protein-drug Binding
Factors affecting protein drug binding
Significance of protein/tissue binding of drug
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
It is defined as “the predictive mathematical model that describes the relationship between in vitro property (such as rate & extent of dissolution) of a dosage form and in vivo response (such as plasma drug concentration or amount of drug absorbed)”.
KINETICS OF MULTIPLE DOSING under the Unit Multicompartment Models According to New PCI syllabus 2017 by Ms. Preeti Patil-Vibhute, Assistant Professor, Sarojini College of Pharmacy, Kolhapur.
Regulations in India (ASU DTAB, ASU DCC), Regulation of
manufacture of ASU drugs - Schedule Z of Drugs & Cosmetics Act for ASU drugs.
Introduction
Regulatory Requirements
Key function of regulatory agencies
Regulation in India
DRUG TECHNICAL ADVISORY BOARD
Drugs Consultative committee-DCC
Schedule Z of Drugs & Cosmetics Act for ASU drugs.
It is defined as “the predictive mathematical model that describes the relationship between in vitro property (such as rate & extent of dissolution) of a dosage form and in vivo response (such as plasma drug concentration or amount of drug absorbed)”.
KINETICS OF MULTIPLE DOSING under the Unit Multicompartment Models According to New PCI syllabus 2017 by Ms. Preeti Patil-Vibhute, Assistant Professor, Sarojini College of Pharmacy, Kolhapur.
Regulations in India (ASU DTAB, ASU DCC), Regulation of
manufacture of ASU drugs - Schedule Z of Drugs & Cosmetics Act for ASU drugs.
Introduction
Regulatory Requirements
Key function of regulatory agencies
Regulation in India
DRUG TECHNICAL ADVISORY BOARD
Drugs Consultative committee-DCC
Schedule Z of Drugs & Cosmetics Act for ASU drugs.
Bioavailability and bioequivalence studyMcpl Moshi
BCS is a scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability.
It is a drug development tool that allows estimation of solubility, dissolution and intestinal permeability affect that oral drug absorption.
Kashikar V S
PES Modern College of Pharmacy ( for ladies), Moshi Pune
Bioavailability and Bioequivalence studyMcpl Moshi
Bioavailability and Bioequivalence study, BCS is a scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability.
It is a drug development tool that allows estimation of solubility, dissolution and intestinal permeability affect that oral drug absorption.
liquisolid technology is a topic related to pharmaceutics presented by konatham teja kumar reddy from chilkur balaji college of pharmcy ,hyderabad,telangana
A note on Microsperes , general introduction and method of preparationsNEELAMSOMANI4
This presentation is related to Microspheres. Microspheres as a part of novel drug delivery system relevant to Pharmaceutics. The general introductions and methodology is described that will be helpful to all pharmacy students .
The presentation provides a concise information regarding various methods or techniques for enhancing solubility of different drugs and will prove useful to students & researchers.
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
Similar to Methods of enhancing Dissolution and bioavailability of poorly soluble drugs (20)
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For more information, visit-www.vavaclasses.com
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Students, digital devices and success - Andreas Schleicher - 27 May 2024..pptxEduSkills OECD
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This presentation provides a briefing on how to upload submissions and documents in Google Classroom. It was prepared as part of an orientation for new Sainik School in-service teacher trainees. As a training officer, my goal is to ensure that you are comfortable and proficient with this essential tool for managing assignments and fostering student engagement.
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2. Bioavailability
Bioavailability is one of the important pharmacokinetic properties of drugs which are used to describe
the fraction of an administered dose of unchanged drug that reaches the systemic circulation.
When a drug is administered intravenously, its bioavailability is 100%. However, if the drug is
administered through other routes (such as oral), its bioavailability decreases because of incomplete
absorption or first pass metabolism.
2
The measurement of the amount of the drug in the plasma
at fixed time intervals indirectly represents the rate and
extent at which the active drug moiety is absorbed from
the drug product and becomes available at the site of
action.
Bioavailability is an essential tool in pharmacokinetics,
which is used for calculating dosages for non intravenous
routes of administration.6/29/2020 Dept.of Pharmaceutics, KCP, CBE - 32
3. Poor aqueous solubility and/ or slow dissolution rate in
the biologic fluids
3
METHODS FOR ENHANCEMENT OF THE BIOAVAILABILITY
Poor stability of the dissolved drug at the physiologic pH
Inadequate partition coefficient and thus poor
permeation through the biological membrane
Extensive presystemic metabolism
6/29/2020 Dept.of Pharmaceutics, KCP, CBE - 32
4. Approaches used to overcome the bioavailability
problems
4
It is done by modifying of
formulation, manufacturing processes
or physiochemical properties of the
drug are done.
Pharmaceutics
approach
Alteration of pharmacokinetic
parameters by modifying its chemical
structure.
Pharmacokinetic
approach
The route of administration is changed in this
method. Solubility and rate of dissolution are very
important factors in third approach.
Biological
approach
6/29/2020 Dept.of Pharmaceutics, KCP, CBE - 32
5. Methods for enhancing bioavailability
Micronization:
• The process involves reducing the size of the
solid drug particles to 1 to 10 microns commonly
by spray drying or by use of air attrition methods
(fluid energy mill).
• Examples of drugs whose bioavailability have been
increased by micronization include griseofulvin
and several steroidal and sulfa drugs.
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6. Methods for enhancing bioavailability
2. Use of Surfactants :
• The surface-active agents enhance dissolution rate
primarily by promoting wetting and penetration of
dissolution fluid into the solid drug particles.
• They are generally used in concentra-tion below their
critical micelle concentration (CMC) values since above
CMC, the drug entrapped in the micelle structure fails
to partition in the dissolution fluid.
• Nonionic surfactants like polysorbates are widely used.
• Examples of drugs whose bioavailability have been
increased by use of surfactants in the formulation
include steroids like spironolactone.
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7. Methods for enhancing bioavailability
3. Use of Salt Forms :
Salts have improved solubility and dissolution
characteristics in comparison to the original
drug.
Alkali metal salts of acidic drugs like
penicillins and strong acid salts of basic drugs
liKe atropine are more water-soluble than the
parent drug.
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8. Methods for enhancing bioavailability
4. Alteration of pH of the Drug Microenvironment :
This can be achieved in two ways—in situ salt formation, and addition of buffers to the formulation
e.g. buffered aspirin tablets.
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9. Methods for enhancing bioavailability
5. Use of Metastable Polymorphs :
A metastable polymorph is more
soluble than the stable polymorph of a
drug that exhibits polymorphism—for
example, the B form of
chloramphenicol palmitate is more
water soluble than the A and the C
forms.
96/29/2020 Dept.of Pharmaceutics, KCP, CBE - 32
10. Methods for enhancing bioavailability
6. Solute-Solvent Complexation :
Solvates of drugs with organic solvents (also called as pseudopolymorphs) generally have higher
aqueous solubility than their respective hydrates or the original drug.
Much higher solubility can be attained by freeze drying such a solute in solution with an organic
solvent with which it is known to form a solvate.
Such a process results in a powder of particles of submicron size, e.g. 1:2 griseofulvin-benzene
solvate.
However, one should take care that the solvent is nontoxic.
106/29/2020 Dept.of Pharmaceutics, KCP, CBE - 32
11. Methods for enhancing bioavailability
7. Solvent Deposition :
In this method, the poorly aqueous soluble drug such as nifedipine is dissolved in an organic solvent like
alcohol and deposited on an inert, hydrophilic, solid matrix such as starch or micro-crystalline cellulose
by evaporation of solvent.
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12. Methods for enhancing bioavailability
8. Selective Adsorption on Insoluble Carriers :
• A highly active adsorbent such as the inorganic clays like
bentonite can enhance the dissolution rate of poorly
water soluble drugs such as griseofulvin, indomethacin
and prednisone by maintaining the concentration gradient
at its maximum.
• The two reasons suggested for the rapid release of
drugs from the surface of clays are—the weak physical
bonding between the adsorbate and the adsorbent, and
hydration and swelling of the clay in the aqueous media. 126/29/2020 Dept.of Pharmaceutics, KCP, CBE - 32
13. Methods for enhancing bioavailability
9. Solid Solutions :
The three means by which the particle size of a drug can be reduced to submicron level are
i. use of solid solutions,
ii. use of eutectic mixtures, and
iii. use of solid dispersions.
In all these cases, the solute is frequently a poorly water soluble drug acting as the guest and the solver is a
highly water-soltible compound or polymer acting as a host or carrier.
A solid solution is a binary system comprising of a solid solute molecularly dispersed in a solid solvent. Since
the two components crystallize together in a homogeneous one phase system, solid solutions are also called as
molecular dispersions or mixed crystals. 13Dept.of Pharmaceutics, KCP, CBE - 32
14. Methods for enhancing bioavailability
9. Solid Solutions :
Because of reduction in particle size to the molecular level, solid solutions
show greater aqueous solubility and faster dissolution than eutectics and
solid dispersions.
They are generally prepared by fusion method whereby a physical mixture
of solute and solvent are melted together followed by rapid solidification.
Such systems, prepared by fusion, are often called as melts e.g.
griseofulvin-succinic acid The griseofulvin from such solid solution
dissolves 6 to 7 times faster than pure griseofulvin.
146/29/2020 Dept.of Pharmaceutics, KCP, CBE - 32
15. Methods for enhancing bioavailability
If the diameter of solute molecules is less than 60% of diameter of solvent molecules or its volume less
than 20% of volume of solvent molecule, the solute molecule can be accommodated within the
intermolecular spaces of solvent molecules e.g. digitoxin-PEG 6000 solid solution. Such systems show
faster dissolution.
When the resultant solid solution is a homogeneous transparent and brittle system, it is called as glass
solution.
Carriers that form glassy structure are citric acid, urea, PVP and PEG and sugars such as dextrose,
sucrose and galactose.
156/29/2020 Dept.of Pharmaceutics, KCP, CBE - 32
16. Methods for enhancing bioavailability
The two mechanisms suggested for enhanced solubility and rapid dissolution of molecular dispersions are:
1. When the binary mixture is exposed to water, the soluble carrier dissolves rapidly leaving the
insoluble drug in a state of micro-crystalline dispersion of very fine particles, and
2. When the solid solution, which is said to be in a state of randomly arranged solute and solvent
molecules in the crystal lattice, is exposed to the dissolution fluid, the soluble carrier dissolves
rapidly leaving the insoluble drug stranded at almost molecular level.
166/29/2020 Dept.of Pharmaceutics, KCP, CBE - 32
17. Methods for enhancing bioavailability
10. Eutectic Mixtures :
These systems are also prepared by fusion
method. Eutectic melts differ from solid
solutions in that the fused melt of solute-
solvent show complete miscibility but
negligible solid-solid solu-bility i.e. such
systems are basically intimately blended
physical mixture of two crystalline
components.
When the eutectic mixture is exposed to
water, the soluble carrier dissolves leaving
the drug in a microcrystalline state which
solubilizes rapidly.
176/29/2020 Dept.of Pharmaceutics, KCP, CBE - 32
18. Methods for enhancing bioavailability
10. Eutectic Mixtures :
Examples of eutectics include paracetamol-urea, griseofulvin-urea, griseofulvin-succinic acid,
etc.
Solid solutions and eutectics, which are basically melts, are easy to prepare and economical
with no solvents involved.
The method however cannot be applied to:
—drugs which fail to crystallize from the mixed melt,
--thermolabile drugs, and
—carriers such as succinic acid that decompose at their melting point.
The eutectic product is often tacky, intractable or irregular crystals.
186/29/2020 Dept.of Pharmaceutics, KCP, CBE - 32
19. Methods for enhancing bioavailability
11. Solid Dispersions :
These are generally prepared by solvent or co-precipitation method whereby both the guest solute and
the solid carrier solvent are dissolved in a common volatile liquid solvent such as alcohol.
The liquid solvent is removed by evaporation under reduced pressure or by freeze drying which results
in amorphous precipitation of guest in a crystalline carrier.
Thus, the basic difference between solid dispersions and solid solutions/eutectics is that the drug is
precipitated out in an amorphous form in the former as opposed to crystalline form in the latter; e.g.
amorphous sulfathiazole in crystalline urea. Such dispersions are often called as co-evaporates or co-
precipitates.
196/29/2020 Dept.of Pharmaceutics, KCP, CBE - 32
20. Methods for enhancing bioavailability
11. Solid Dispersions :
The method is suitable for thermolabile substances but has a number of disadvantages like
higher cost of processing, use of large quantities of solvent, difficulty in complete removal of
solvent, etc.
The carriers used are same as for eutectics or solid solutions. With glassy materials, the
dispersions formed are called as glass dispersions or glass suspensions.
206/29/2020 Dept.of Pharmaceutics, KCP, CBE - 32
21. Methods for enhancing bioavailability
12. Molecular Encapsulation with Cyclodextrins :
The beta- and gamma-cyclodextrins and several of their derivatives are unique in having the ability to form molecular
inclusion complexes with hydrophobic drugs having poor aqueous solubility.
These cyclodextrin molecules are versa-tile in having a hydrophobic cavity of size suitable enough to accommodate the
lipophilic drugs as guests; the outside of the host molecule is relatively hydrophilic
Thus, the molecularly encapsulated drug has greatly improved aqueous solubility and dissolution rate.
There are several examples of drugs with improved bioavailability due to such a phenomena—thiazide diuretics,
barbiturates, benzodiazepines and a num-ber of NSAIDs.
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