This document discusses various concepts related to pharmacokinetics including drug absorption, distribution, metabolism, and excretion. It describes how drugs pass through cell membranes via passive diffusion, facilitated transport, or active transport. Factors affecting drug absorption like solubility, ionization, and pharmaceutical formulation are also summarized. The concepts of bioavailability, plasma half-life, and steady state are defined. The document also discusses distribution of drugs to tissues, factors influencing distribution, and drug clearance through metabolism and excretion.
Best slides ever of theories of drug dissolution, film teory, dankwerts model, interfacial model of dissolution, noyes whitneys equation, modified noyes whitney equation, sink condition, 1st order & zero order kinetics of drug dissolution, conclution, references
Methods of enhancing Dissolution and bioavailability of poorly soluble drugsRam Kanth
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Topic: Methods of Enhancing Bioavailability
Several approaches discussed are
1. Micrnoization
2. Use of Surrfactants
3. Use of Salt forms
4. Alteration of pH of microenvironment
5. Use of metastable polymorphs
6. Solute-Solvent Complexation
7. Solvent Deposition
8. Selective Adsorption on Insoluble Carriers
9. Solid Solutions
10. Eutectic Mixtures
11. Solid Dispersions
12. Molecular Encapsulation with Cyclodextrins
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Thank you all for watching this presentation.
Best slides ever of theories of drug dissolution, film teory, dankwerts model, interfacial model of dissolution, noyes whitneys equation, modified noyes whitney equation, sink condition, 1st order & zero order kinetics of drug dissolution, conclution, references
Methods of enhancing Dissolution and bioavailability of poorly soluble drugsRam Kanth
Greetings!
Good Day to all...
Topic: Methods of Enhancing Bioavailability
Several approaches discussed are
1. Micrnoization
2. Use of Surrfactants
3. Use of Salt forms
4. Alteration of pH of microenvironment
5. Use of metastable polymorphs
6. Solute-Solvent Complexation
7. Solvent Deposition
8. Selective Adsorption on Insoluble Carriers
9. Solid Solutions
10. Eutectic Mixtures
11. Solid Dispersions
12. Molecular Encapsulation with Cyclodextrins
Please do clarify for doubts if any....
Thank you all for watching this presentation.
The slides describe concept of distribution, Volume of distribution, factors affecting volume of distribution and the barriers to distribution. Blood brain barrier and placental barrier.
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
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..
Drug distibution, significance, steps in Drug distribution, Factors affecting,physiochemical properties of drug, volume of distribution,protein binding, mechanism of protein drug binding
A detailed study on every aspects of parenteral :- introduction, preformulation factors, essential requirements, vehicles and additives, isotonicity, production procedure, facilities, and controls, container and closure selection and finally the quality control evaluation of parenterals.
Pharmacokinetics is the study of the movement of drug molecules in the body. It includes absorption, distribution, metabolism, and excretion of drugs. Pharmacokinetics is the study of what happens to drugs once they enter the body (the movement of the drugs into, within, and out of the body). For a drug to produce its specific response, it should be present in adequate concentrations at the site of action. This depends on various factors apart from the dose.
Four pharmacokinetic properties determine the onset, intensity, and the duration of drug action (Figure 1.6.1):
• Absorption: First, absorption from the site of administration permits entry of the drug (either directly or indirectly) into plasma.
• Distribution: Second, the drug may then reversibly leave the bloodstream and distribute it into the interstitial and intracellular fluids.
• Metabolism: Third, the drug may be biotransformed by metabolism by the liver or other tissues.
• Elimination: Finally, the drug and its metabolites are eliminated from the body in urine, bile, or feces.
In short, pharmacokinetics means what the body does to the drug.
The slides describe concept of distribution, Volume of distribution, factors affecting volume of distribution and the barriers to distribution. Blood brain barrier and placental barrier.
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
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..
Drug distibution, significance, steps in Drug distribution, Factors affecting,physiochemical properties of drug, volume of distribution,protein binding, mechanism of protein drug binding
A detailed study on every aspects of parenteral :- introduction, preformulation factors, essential requirements, vehicles and additives, isotonicity, production procedure, facilities, and controls, container and closure selection and finally the quality control evaluation of parenterals.
Pharmacokinetics is the study of the movement of drug molecules in the body. It includes absorption, distribution, metabolism, and excretion of drugs. Pharmacokinetics is the study of what happens to drugs once they enter the body (the movement of the drugs into, within, and out of the body). For a drug to produce its specific response, it should be present in adequate concentrations at the site of action. This depends on various factors apart from the dose.
Four pharmacokinetic properties determine the onset, intensity, and the duration of drug action (Figure 1.6.1):
• Absorption: First, absorption from the site of administration permits entry of the drug (either directly or indirectly) into plasma.
• Distribution: Second, the drug may then reversibly leave the bloodstream and distribute it into the interstitial and intracellular fluids.
• Metabolism: Third, the drug may be biotransformed by metabolism by the liver or other tissues.
• Elimination: Finally, the drug and its metabolites are eliminated from the body in urine, bile, or feces.
In short, pharmacokinetics means what the body does to the drug.
Pharmacokinetics (PK) is the study of how the body interacts with administered substances for the entire duration of exposure (medications for the sake of this article). This is closely related to but distinctly different from pharmacodynamics, which examines the drug’s effect on the body more closely. The four main parameters generally examined by this field include absorption, distribution, metabolism, and excretion (ADME). Wielding an understanding of these processes allows practitioners the flexibility to prescribe and administer medications that will provide the greatest benefit at the lowest risk and allow them to make adjustments as necessary, given the varied physiology and lifestyles of patients.
When a provider prescribes medication, it is with the ultimate goal of a therapeutic outcome while minimizing adverse reactions. A thorough understanding of pharmacokinetics is essential in building treatment plans involving medications. Pharmacokinetics, as a field, attempts to summarize the movement of drugs throughout the body and the actions of the body on the drug. By using the above terms, theories, and equations, practitioners can better estimate the locations and concentrations of a drug in different areas of the body.
The appropriate concentration needed to obtain the desired effect and the amount needed for a higher chance of adverse reactions is determined through laboratory testing. Using the equations given above, a clinician can easily estimate safe medication dosing over a period of time and how long it will take for a medication to leave a patient’s system. These are, however, statistically-based estimations, influenced by differences in the drug dosage form and patient pathophysiology. This is why a deep understanding of these concepts is essential in medical practice so that improvisation is possible when the clinical situation requires it.
This presentation includes the detail information of pharmacokinetics. How body react with drug. Route of drug administration. In this presentation there is a given all the relevant data related to the general pharmacology which is used full for the D. pharm, B. Pharm, Pharm D students . Pharmacodynamics : - What drug does to body.
Pharmacokinetics : - What body does to the drug.
Pharmacotherapeutics : - Use of drugs in prevention & treatment of disease.
Clinical pharmacology : - Scientific study of drugs in man.
Toxicology : - Aspect of pharmacology deals with adverse effects of Drugs.
Pharmacodynamic agents : - Designed to have pharmacodynamic effects in the
recipient.
Chemotherapeutic agents : - Designed to inhibit/kill parasites/malignant cells & does not have or
with minimal pharmacodynamic effects in recipient.
Orphan drugs : - Drugs or Biological Products for diagnosis/treatment/ Prevention of a
rare disease.
E.g.:- Liothyronine (T3), Desmopressin, Baclofen, Digoxin Antibody.PHARMACOKINETICS
Absorption of Drugs:-
A) Simple diffusion: - Bidirectional process rate of transfer across the membrane is proportional to
concn gradient. E.g.:- H20 soluble drugs with low mol-wt, lipid soluble drugs.
B) Active transport: - requires energy – independent of physical properties of membrane. E.g.:- H20
soluble drugs with high mol-wt.
Carrier mediated transport: - E.g.:- Intestinal absorption of Ca2+
.
C) Pinocytosis: - Important in unicellular organisms like Amoeba.
Bioavailability: - Amount of drug reaches systemic circulation following a non-vascular drug
administration.
Auc oral
F = Auc iv
Barriers:-
B.B.B:- made up of choroid cells (strong Barrier).
Testis Barrier: - made up of seroid cells.
Placental Barrier: - made up of sertoli cells (weak Barrier).
Endothelial Barrier: - in all blood cells (very weak).
For absorption of vitB12, IF factor is required which is synthesized by parietal cells?2 types of metabolism: - a. Non synthetic reaction (phase I reaction)
i. Oxidation
ii. Reduction
iii. Hydrolysis
iv. Cyclilization
v. Decyclilization
b. Synthetic reaction (Phase II reaction) conjugation reactions
i. Glucoronide conjugation
ii. Acetylation
iii. Methylation
iv. Sulfate conjugation
v. Glycine conjugation
vi. Glutathion conjugation Remember:- Many drugs are eliminated by the kidney without being.
Pharmacokinetics (Greek: Kinesis—movement)
This refers to movement of the drug in and alteration of the drug by the body; includes absorption, distribution, binding/ localization/ storage, biotransformation and excretion of the drug.
Bioavailability: is a subcategory of absorption.
Bioavailability is a measurement of the rate and extent to which a drug reaches at the site of action determined by its concentration-time curve in blood or by its excretion in urine.
Two preparations of a drug are considered bioequivalent when the rate and extent of bioavailability of the active drug from them is not significantly different under suitable test conditions
The clearance of a drug is the theoretical volume of plasma from which the drug is completely removed in unit time.
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The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
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2. PASSAGE OF DRUG ACROSS CELL MEMBRANE
Ability of drug to cross cell membrane
Molecular size and shape
Solubility at the site of absorption, degree of ionization and
lipid solubility.
Passive diffusion:
Concentration gradient
Depend upon lipid solubility and ionization
Unionized drugs are more lipid soluble.
Filtration:
Water soluble drugs
Through porous membrane
Hydrostatic pressure or osmotic pressure
3. 2. FACILITATED DIFFUSION
Specialized transmembrane carrier proteins
These carrier proteins undergo conformational changes
Allowing the passage of drugs or endogenous.
It does not require energy, can be saturated, and may be
inhibited by compounds that compete for the carrier.
3. Active transport:
involves specific carrier proteins
Energy-dependent active transport is driven by the hydrolysis
of adenosine triphosphate.
It is capable of moving drugs against a concentration gradient.
The process is saturable, selective and may be compete
inhibited by other cotransported substances.
4. 4. ENDOCYTOSIS AND EXOCYTOSIS
This type of absorption is used to transport drugs of
exceptionally large size across the cell membrane.
Endocytosis involves engulfment of a drug by the cell
membrane and transport into the cell by pinching off the
drugfilled vesicle.
Exocytosis is the reverse of endocytosis..
5. ABSORPTION
Absorption is the transfer of a drug from its site of administration
to the blood stream.
Factors affecting drug absorption
1.Solubility:
Higher lipid soluble – greater absorption rate
Aqueous solution rapidly absorbed than those given in oily
solution, suspension or solid form.
2.Degree of ionization:
Greater ionization – less absorption
Lipid soluble are in unionized form – readily absorbed
Water soluble drugs are in ionized form – can be absorbed –
very small molecular size
6. 3.Effect of PH on drug absorption
Most of drug are either weak acid or weak bases
Acidic drug (HA) release proton causing a charged anion to
form
Weak bases (BH+) can also release H+ ion. Protonated form
of basic drug is usually charged.
4. Pharmaceutical preparation:
Solution are better absorbed than suspension
Smaller the particle size of powders the more efficient their
absorption.
5. Route of administration:
Parenteral routs is rapid than oral route
Intramuscular route is rapid than from subcutaneous route
7. 6. Surface area:
Greater surface, larger will be the amount of drug absorbed
7. Concentration of drug:
Greater concentration of the drug, greater will be the
concentration gradient
8. Local blood flow:
Rate of absorption is directly proportional to the local blood
circulation
8. FACTORS MODIFYING ABSORPTION FROM GUT
1.Motility of the Gut:
Helps in dissolution of tablets, increase the motility also increase rate
of absorption
2.Ph of the Gut:
Weak acid are mostly unionized in acid medium- better absorbed
Weak bases are unionized in alkaline medium- better absorbed
3.Disease condition:
Effect rate of absorption
4.Presence of other substance:
9. Plasma half-life:
Time it takes for the plasma concentration or the amount of drug in
the body to be reduced by 50%.
The half-life of a drug depends on its clearance and volume of
distribution
E.g For example, after intravenous administration, if maximum
concentration is 16 mg and the half life is 2 hours, after 2 hours 8 mg
will be left, and so on.
Factors affecting half-life
Clearance decrease
Volume of distribution
10. Steady state:
Steady state concentration of drug occurs when the rate of drug
elimination is equal to the rate of drug administration.
Steady state plasma concentration is directly proportional to rate of
infusion and inversely proportional to the total body clearance of the
drug.
Biological half life:
The biological half-life or terminal half-life of a substance is the time it
takes for a substance to lose half of its pharmacologic, physiologic,
or radiologic activity,
11. BIOAVAILABILITY
The fraction of unchanged drug reaching the systemic
circulation following administration by any route”
or
The percentage of administered drug that reaches the systemic
circulation in a chemically unchanged form”
Thus by definition a drug that is administered by intravenous
route has 100% bioavailability
12. FACTORS AFFECTING BIOAVAILABILITY
1-Rout of administration:
2-First-pass hepatic metabolism:
when a drug is absorbed across GIT, it enters the portal circulation
before entering the systemic circulation.
If the drug is rapidly metabolized by the liver ,the amount of unchanged
drug that gains access to the systemic circulation is decreased
3-Absorption
4-Solubility of the drug:
hydrophobic drug will absorb more so bioavailability will be more
5-Chemical instability:
some drugs are unstable in pH of the gastric contents. Others are
destroyed in GIT by degradative enzymes
6-Particle size: smaller the particle size more absorption will be there.
13. DISTRIBUTION OF DRUGS
Process by which drug reversibly leave blood stream and
enter interstitial and tissue.
Such as plasma, extra cellular and intracellular fluid
depending upon its physicochemical properties.
Substance of high molecular weight almost remain in water
plasma.
Drug that can pass capillary wall but can not pass across the
cell membrane are localized mainly in extra cellular fluid. E.g
mannitol iv administration
Cross cell membrane and do not have specific affinity for
specific tissue are distributed equally. E.g alcohol , urea
Some drugs are concentrated especially in one or more tissue
of the body. E.g. iodide in thyroid gland
14. FACTORS THAT DETERMINE DRUG
DISTRIBUTION
1. Binding of drug to plasma protein and tissues
Binding to plasma protein
Bound to plasma protein to varying extent
Binding of drug to albumin is reversible and may show
low or high capacity
Albumin has the strongest affinity for anionic drugs and
hydrophobic drugs.
Binding to tissue protein
Drug accumulate in tissue leading to higher conc. In
tissue.
As result of binding to lipid, protein or nucleic acid.
Drug may also be actively transported into tissue.
Tissue reservoirs may serve as major source of the drug
and prolong its action
15. BLOOD FLOW
How rapidly drug molecules are delivered to a given tissue
How effectively the conc. Gradient b/w blood and tissue is
maintained
Drug equilibrate rapidly b/w the blood and organs with high
blood flow
Capillary permeability
Capillary structure and chemical nature of drug.
16. LIPOPHILICITY
Lipophilic drug readily move across most biologic
membranes
Dissolved and penetrate entire cell surface
Hydrophilic drug do not readily penetrate cell
membrane and must pas through slit junction.
17. DRUG METABOLISM/BIOTRANSFORMATION
The series of chemical alterations of drug that occurs
within the body
How activity of drug terminated or altered.
Some drug – excrete through kidney – no need of
metabolism.
Lipophilic– promote- biological membrane- site of
action- reduce elimination
Lipophilic drug convert into hydrophilic metabolites-
terminate biological activity and eliminate from the body.
Site of drug metabolism:
liver, kidney, GIT, skin and lungs
18. ENZYME
Cytochrome P-450 system
Drug- elevate level of cytochrome p-450- increase rate of
metabolism– reduce action and duration of the drug.
Drug– inhibit p-450 system and may potentate the action of
other drug that are metabolized by this system
19. PHASES OF METABOLISM
First phase I and than Phase II
Some drug pass through phase II and the phase I
Some drug directly undergo through phase II.
Phase I:
Generally result in loss of pharmacological activity of drug
Increase pharmacologically inactive become active after
metabolism
Conversion of drug to a toxic compound
Reaction include in type I reaction are
Oxidative reaction
Reduction reaction
hydrolysis
.
20. PHASE II REACTION
o Conjugation of the parent compound with certain acid radical or
amino acids
o Metabolite from phase I metabolism is sufficient polar – excreted
by kidneys
o Many metabolite are too lipophilic to be excreted and they must
undergo conjugation reaction with endogenous substrate
o Phase II reaction result in inactivation of the parent drug but not
always
o Phase II reaction
o Glucuronidation
o Acetylation
o Glutathion conjugation
o Sulfate conjugation
o Methylation
o Water conjugation
21. FACTOR AFFECTING BIOTRANSFORMATION
Difference in drug distribution, metabolism and elimination due
to following factor
Individual difference:
Different people have different level of metabolism
Genetic factors:
Influence enzyme levels resulting in difference in drug
metabolism
Diet and environmental factors:
Certain vegetables and fruits induce or inhibit enzymes
affecting the drug metabolism
Age and Sex;
Drug have more effect and more toxicity – young and old
patient due decrease drug metabolism
In newborn the enzyme in the liver are not developed.
Male have more rapid drug metabolism than female.
22. Drug – Drug interaction
Interaction b/w drugs and endogenous compounds
Diseases affecting drug metabolism
Pharmacokinetic factors
23. CLEARANCE OF DRUG
Clearance estimates the amount of drug cleared
from the body per unit of time.
First order kinetics: if a constant fraction of drug is
eliminated per unit time, it is called first order kinetic
e.g. 5% or 10%
Zero order kinetics: if a constant amount of drug is
eliminated per unit time it is called first order
kinetics, e.g. 5mg or 10 mg
24. DRUG CLEARANCE THROUGH METABOLISM
Major route of elimination hepatic metabolism, biliary
elimination and urinary elimination,
Elimination processes decrease plasma concentration.
Constant fraction of drug present is eliminated in given unit of
time
A. Kinetics of metabolism:
First order kinetics: if a constant fraction of drug is eliminated
per unit time, it is called first order kinetic e.g. 5% or 10%
Zero order kinetics: if a constant amount of drug is eliminated
per unit time it is called first order kinetics, e.g. 5mg or 10 mg
25. B: Reaction of drug metabolism:
Kidney can not eliminate lipophilic drug
First metabolized lipid soluble into more polar in the
liver through phase I and phase II.
26. DRUG CLEARANCE BY THE KIDNEY
Polar to be eliminated
Eliminate through kidney
Glomerular filtration
Proximal tubular secretion
Distal tubular reabsorption
27. CLEARANCE BY OTHER ROUTE
Intestine, bile lungs and breast milk
Orally not absorbed directly eliminate through
intestine or into bile eliminate in the faces.
Lung – anesthetic gases
Excretion of most drugs into sweat, saliva, tears,
hair and skin.