1) Oral absorption of drugs depends on physiological factors like the physicochemical properties of the drug, the dosage form, and the anatomy and physiology of the absorption site.
2) Key factors affecting absorption include the drug's pH, solubility, and lipid solubility. Absorption also depends on formulation factors like tablet disintegration and dosage form as well as patient factors like gastric emptying rate.
3) Drugs are absorbed through the gastrointestinal tract via both transcellular transport mechanisms like passive diffusion and carrier-mediated transport, as well as paracellular transport like bulk flow. The rate and extent of absorption can be impacted by the drug's properties and the route of administration.
A presentation given by a group of students of Faculty of Pharmacy, University of Dhaka, Bangladesh.
This presentation discussed with different physiolgical factors of drug absorption, structure of membrane the drug crosses, different transport mechanism etc
PHARMACOKINETIC MODELS
Drug movement within the body is a complex process. The major objective is therefore to develop a generalized and simple approach to describe, analyse and interpret the data obtained during in vivo drug disposition studies.
The two major approaches in the quantitative study of various kinetic processes of drug disposition in the body are
Model approach, and
Model-independent approach (also called as non-compartmental analysis).
Fundamental concept of modified drug releaseAbhinayJha3
Different Terminologies used in a modified release
1. Sustained release
2. Delayed release
3. Prolonged release
4. Extended-release
5. Controlled release
6. Site-specific targeting and receptor targeting
SELECTION OF DRUG CANDIDATE FOR ORAL SUSTAINED RELEASE SYSTEMS, BIOPHARMACEUTICAL CLASSIFICATION SYSTEM.
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.
DISSOLUTION
Dissolution is defined as a process in which a solid substance solubilises in a given solvent.
(i.e. mass transfer from the solid surface to the liquid phase.)
Three Theories:
Diffusion layer model / Film theory
Danckwert’s model / Penetration or Surface renewal theory
Interfacial barrier model / Double barrier or Limited solvation theory
Dosage form design - Biopharmaceutical considerationAniruddha Roy
Dosage form design - Biopharmaceutical consideration: Understanding how physicochemical characteristics of a drug and formulation component affect bioactivity
A presentation given by a group of students of Faculty of Pharmacy, University of Dhaka, Bangladesh.
This presentation discussed with different physiolgical factors of drug absorption, structure of membrane the drug crosses, different transport mechanism etc
PHARMACOKINETIC MODELS
Drug movement within the body is a complex process. The major objective is therefore to develop a generalized and simple approach to describe, analyse and interpret the data obtained during in vivo drug disposition studies.
The two major approaches in the quantitative study of various kinetic processes of drug disposition in the body are
Model approach, and
Model-independent approach (also called as non-compartmental analysis).
Fundamental concept of modified drug releaseAbhinayJha3
Different Terminologies used in a modified release
1. Sustained release
2. Delayed release
3. Prolonged release
4. Extended-release
5. Controlled release
6. Site-specific targeting and receptor targeting
SELECTION OF DRUG CANDIDATE FOR ORAL SUSTAINED RELEASE SYSTEMS, BIOPHARMACEUTICAL CLASSIFICATION SYSTEM.
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.
DISSOLUTION
Dissolution is defined as a process in which a solid substance solubilises in a given solvent.
(i.e. mass transfer from the solid surface to the liquid phase.)
Three Theories:
Diffusion layer model / Film theory
Danckwert’s model / Penetration or Surface renewal theory
Interfacial barrier model / Double barrier or Limited solvation theory
Dosage form design - Biopharmaceutical considerationAniruddha Roy
Dosage form design - Biopharmaceutical consideration: Understanding how physicochemical characteristics of a drug and formulation component affect bioactivity
- Routes of administration
- First pass metabolism, bioavailablilty, drug distribution,
- Drug interactions with proteins, Drug metabolism, elimination, Half-life
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.
General pharmacology Diploma in pharmacy second year YogeshShelake
The General pharmacology ,Toxicology & Pharmacotherapeutics
To Undastanding the general pharmacology & Definitions of PHARMACODYNAMECIS ,PHARMACOKINITICS (Absorbation,Distribution,Metabolism,Excreation )Pharmacology ,Toxicology ,Pharmacotherapeutic ,
Advantages of Routs of Administration & Their Disadvantages
Factors affecting of absorpation ,excreation of drug,factor modifing deug action
Announcement about my previous presentations - Thank youAreej Abu Hanieh
ANNOUNCEMENT Thank you for all of you, my followers who sent me messages with a lot of love and appreciations, I finally graduated after 6 years of studying in Birzeit University , In doctor of Pharmacy department I hope all of you benefited from all the presentations posted before Thank you a new PharmD GraduatedAreej ^^
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
1. Physiological Factors Affecting
Oral Absorption
The ultimate goal of PK is to have the drug reach the site
of action in a concentration which produces a
pharmacological effect. No matter how the drug is given
(other than IV) it must pass through a number of
biological membranes before it reaches the site of action.
2. Pharmacokinetics of Drug Absorption
• The systemic drug absorption from the
gastrointestinal (GI) tract or from any other
extravascular site is dependent on:
1) The physicochemical properties of the drug.
2) The dosage form used.
3) The anatomy and physiology of the absorption
site.
4. The physicochemical properties of the drug
• pH - partition theory
– For a drug to cross a membrane barrier it must normally
be soluble in the lipid material of the membrane to get
into membrane, also it has to be soluble in the aqueous
phase as well to get out of the membrane.
– Most drugs have polar and non-polar characteristics or
are weak acids or bases.
– For drugs which are weak acids or bases the pKa of the
drug and the pH of the GI tract fluid and the pH of the
blood stream will control the solubility of the drug and
thereby the rate of absorption through the membranes,
lining the GI tract.
5. Formulation factors
• A drug must be in solution to be absorbed from
the GI tract.
• The bioavailability of a drug decrease in the
order:
solution > suspension > capsule > tablet > coated tablet
This order may not always be followed but it is a
useful guide.
6. Pharmacokinetics of Drug Absorption
• For oral dosing, such factors affect the rate
and the extent of drug absorption:
i. surface area of the GI tract.
ii. stomach-emptying rate.
iii. GI mobility.
iv. blood flow to the absorption site.
7. pH Membrane Blood Supply Surface Area Transit Time By-pass liver
BUCCAL approx 7 thin Good, fast
absorption
with low dose
small Short unless
controlled
yes
ESOPHAGUS 5 - 6 Very thick, no
absorption
- small short -
STOMACH 1 - 3
decomposition,
weak acid
unionized
normal good small 30 - 40
minutes,
reduced
absorption
no
DUODENUM 6 - 6.5 bile
duct,
surfactant
properties
normal good very large very short (6"
long), window
effect
no
SMALL
INTESTINE
7 - 8 normal good very large 10 -
14 ft, 80 cm 2
/cm
about 3 hours no
LARGE
INTESTINE
5.5 - 7 - good not very large 4
- 5 ft
long, up to 24
hr
rectum yes
GI Physiology and Drug Absorption
8.
9.
10.
11. Gastric emptying and motility
• Generally drugs are better absorbed in the small
intestine (because of the larger surface area) than in
the stomach, therefore increasing stomach emptying
will increase drug absorption.
• The quicker the stomach emptying the higher the
plasma concentration.
• Also slow stomach emptying can cause increased
degradation of drugs in the stomach's lower pH; e.g.
L-dopa.
12. Food
• Food can effect the rate of gastric emptying.
• For example fatty food can slow gastric emptying
and retard drug absorption. Generally the extent
of absorption is not greatly reduced.
• Occasionally absorption may be improved.
Griseofulvin absorption is improved by the
presence of fatty food. Apparently the poorly
soluble griseofulvin is dissolved in the fat and
then more readily absorbed.
13. • Propranolol plasma concentrations are larger
after food than in fasted subjects. This may be
an interaction with components of the food.
The Effect of Fasting versus Fed on Propranolol Concentrations
14. Passage of Drugs across Biological membrane
• Transport across the membranes
Transcellular transport
Passive diffusion
Carrier-mediated transport
Facilitated diffusion
Active transport
Ion-pair transport
Endocytosis or
Pinocytosis
Paracellular transport
Bulk flow
Filtration
15. Transcellular transport
Passive diffusion
Most (many) drugs cross biologic membranes by passive
diffusion.
Diffusion occurs when the drug concentration on one side of
the membrane is higher than that on the other side. Drug
diffuses across the membrane in an attempt to equalize the
drug concentration on both sides of the membrane.
Drugs that can passively diffuse through cell membrane
must be:
• Lipid soluble
• Unionized form
• Move according to concentration gradient
16.
17. Carrier-mediated transport
1. Facilitated diffusion
Carrier needed
Can be saturated
No energy required
Move along conc. Gradient
e.g. vitamin B12 transport.
2. Active transport
Carrier needed
Can be saturated
Energy required
Move against conc. Gradient
competitive inhibition is possible
E.g. glucose and amino acids
18. 3. Carrier-mediated intestinal transport (P-gp)
• P-glycoprotein (P-gp, MDR-1) is a 170 kDa membrane-bound
protein.
• P-gp transporters are present throughout the body including liver,
brain, kidney and the intestinal tract epithelia.
• This is an active, ATP-dependent process which can have a
significant effect on drug bioavailability.
• They appear to be an important component of drug absorption
acting as reverse pumps generally inhibiting absorption. They
work as efflux transporters and provide a defense mechanism
against harmful substances. They transport certain hydrophobic
substances in the following direction:
Into the gut
Out of the brain
Into bile
Into urine
Out of the gonads
Out of other organs
19. • P-glycoprotein works against a range of drugs such as cyclosporin
A, digoxin, β-blockers, antibiotics and others. This process has
been described as multi-drug resistance (MDR).
• Additionally P-glycoprotein has many substrates in common with
cytochrome P450 3A4 (CYP 3A4) thus it appears that this system
not only transports drug into the lumen but causes the metabolism
of substantial amounts of the drug as well (e.g. cyclosporin).
• Clinically significant substrates of P-gp include digoxin,
cyclosporine, fexofenadine, paclitaxel, nortriptyline and
phenytoin.
• A number of compounds can act as P-gp inhibitors including
atorvastatin, ketoconazole or erythromycin (digoxin AUC
increased) and grapefruit juice (increased paclitaxel absorption).
• Rifampin has been reported to induce P-gp expression.
20. Vesicular Transport
Pinocytosis and phagocytosis
Macromolecules are
transported by
endocytosis or
exocytosis
e.g. Vitamin A, D, E,
and K,
Ion-pair transport
e.g. Propranolol and Quinine
For example, the formation of ion pairs
to facilitate drug absorption has been
demonstrated for propranolol, a basic
drug that forms an ion pair with oleic
acid
21. Paracellular Transport
Pore (convective) Transport
Bulk flow and Filtration
• Very small molecules (such as urea, water, and
sugars) are able to cross cell membranes rapidly,
as if the membrane contained channels or pores.
• Filtration is an important way to excrete drugs
22. Passage of Drugs across Biological membrane
• Drug properties
Molecular weight, shape and size
Small molecules – more chance of crossing
membrane
23. Passage of Drugs across Biological membrane
• Lipid solubility
• Movement directly through the lipid bilayer
requires that the substance dissolve into the lipid
bilayer
Increase lipid solubility causes increased partition coefficient
Increase in partition coefficient causes increased permeability.
Permeability
Kp
24. Ionization
General rules
A drug usually exists in 2 forms – unionized and ionized
forms.
Unionized drug can passively diffuse across membrane
The ratio of unionized drug will indicate direction of
passive diffusion
Factors affecting ionization are
pH of the medium
pKa (acid dissociation constant) of the drug
Acidic drug tend to ionize in more basic medium
pH – pKa = log (ionized / nonionzized)
Basic drug tend to ionize in more acidic medium
pH – pKa = log (nonionized / ionized)24
26. Stomach fluid
pH 2
Plasma
pH 7
More non-ionized Ionized
Less non-ionized Ionized
Example
Acidic drug pKa 6 pH – pKa = log (ionized / non-ionized)
26
27. Some data for practice calculation
pH
Plasma 7.4
CSF 7.4
Stomach 1.4
Small Intestine 8.0
Acidic drug pKa Basic drug pKa
Ampicillin 2.5 Strychnine 8.0
Sulfadiazine 6.5 Aminopyrine 5.0
Aspirin 3.4 Procaine 9.0
27
28. Routes of Drug Administration
• The route of administration (ROA) that is chosen may
have a profound effect upon the speed and efficiency
with which the drug acts.
• Appropriate administration route depends on:
the dosage form in which the drug is available
the patient’s age
the patient’s condition, e.g. level of consciousness
29. Sublingual/buccal
• Some drugs are taken as smaller tablets which are held in the
mouth or under the tongue.
• Advantages:
rapid absorption
drug stability
avoid first-pass effect
Ideal for lipid soluble drugs
Absorption favored of acids with high pka and bases with low pka
• Disadvantages
inconvenient
small doses
unpleasant taste of some drugs
30. Rectal
• Advantages:
unconscious patients and children
if patient is nauseous or vomiting
Bypassing first pass effect (partially)
good for drugs affecting the bowel such as laxatives
• Disadvantages
absorption may be variable
irritating drugs contraindicated
discomfort
31. Intravenous (IV)
• Advantages:
complete bioavailability
precise, accurate and almost immediate onset of action,
large quantities can be given, fairly pain free
• Disadvantages
greater risk of adverse effects
high concentration attained rapidly (anaphylaxis)
risk of embolism
Cost
Drug suspensions cannot be used
32. Subcutaneous
slow and constant absorption
absorption is limited by
blood flow, affected if
circulatory problems exist
concurrent administration
of vasoconstrictor will slow
absorption
Intramuscular
rapid absorption of drugs in aqueous solution
depot and slow release preparations
pain at injection sites for certain drugs
33. Inhalation
• Gaseous and volatile drugs may be inhaled and absorbed
by the pulmonary epithelium and mucous membranes of
respiratory tract.
-almost instantaneous absorption,
-large surface area of alveoli (~72 m2)
-high permeability of alveolar membrane
-avoids first-pass metabolism
• Local application (mainly)
• Difficulties in regulating the exact amount of dosage.
• Sometimes patient having difficulties in giving
themselves a drug by inhaler.
34. Oral Administration
• Advantages:
Generally the safest route
Convenient - can be self- administered, pain free, easy
to take
Absorption - takes place along the whole length of the
GI tract
Cheap - compared to most other parenteral routes
No need for sterile equipment
Variety: tablets, capsules, fast, slow release …..
35. Oral Administration
• Disadvantages
Sometimes inefficient - only part of the drug may be
absorbed.
First-pass effect - drugs absorbed orally are initially
transported to the liver via the portal vein
Irritation to gastric mucosa - nausea and vomiting
Destruction of drugs by gastric acid and digestive juices, gut
flora, mucosal enzymes
Onset of effect is slow
unpleasant taste of some drugs
unable to use in unconscious patient
Food interaction and G-I motility can affect drug absorption
36.
37.
38.
39.
40. Physiological Factors
– Gastric motility
– Gastric emptying time
– pH at the absorption site
– Area of absorbing surface
– Blood flow
– Disease states
– Ingestion with or without food
40
41. Oral drug absorption
Oral cavity:
Saliva is the main secretion (1500
mL/day)
Saliva contains amylases
The pH is 6-7
Highly vascular area
Esophagus:
pH of 5-6
No drug absorption from this site
Very little dissolution
42. Stomach :
The surface area for absorption of drugs is relatively
small in the stomach due to the absence of macrovilli &
microvilli.
Extent of drug absorption is affected by variation in the
time it takes the stomach to empty, i.e., how long the
dosage form is able to reside in stomach.
Drugs which are acid labile must not be in contact with
the acidic environment of the stomach.
pH of 1.5 -2 (fed-state) or 2 – 6 (fasted-state).
HCl secretion of the stomach is stimulated by gastrin and
histamine.
High-density foods generally are emptied from stomach
more slowly.
43. Small Intestine:
Include duodenum, jejunum and ileum.
Major site for absorption of most drugs due to its large
surface area.
The Folds in small intestine called as folds of kerckring,
result in 3 fold increase in surface area.
These folds possess finger like projections called Villi
which increase the surface area 30 times.
From the surface of villi protrude several microvilli which
increase the surface area 600 times.
Blood flow is 6-10 times that of
stomach.
pH Range is 6–7.5 , favorable
for most drugs to remain unionised.
44. Small Intestine:
Peristaltic movement is slow, while transit time is long.
Permeability is high.
The drugs which are predominantly absorbed through the
small intestine, the transit time of a dosage form is the major
determinant of extent of absorption.
the transit time in small intestine for most healthy adults is
between 3 to 4 hours, and a drug may take about 4 to 8 hours
to pass through the stomach & small intestine during fasting
state.
During the fed state, the small intestine transit time may take
about 8 to 12 hours.
45. Large intestine:
Include colon and rectum
Lack villi
Limited absorption from colon
The major function of large intestine is to absorb
water from ingestible food residues which are
delivered to the large intestine in a fluid state, &
eliminate them from the body as semi solid feces.
pH ranging from 5.5-7
Colon contains microorganisms
Only a few drugs are absorbed in this region.
46. Influence of drug pKa and GI pH on
drug absorption
Drugs Site of absorption
Very weak acids (pKa > 8.0) Unionized at all pH values
Absorbed along entire length of GIT
Moderately weak acids (pKa 2.5 – 7.5) Unionized in gastric pH
Ionized in intestinal pH
Better absorbed from stomach
Strong acids (pKa <2.5) Ionized at all pH values
Poorly absorbed from GIT
Very weak bases (pKa < 5) Unionized at all pH values
Absorbed along entire length of GIT
Moderately weak bases (pKa 5 – 11 ) Ionized in gastric pH
Unionized in intestinal pH
Better absorbed from intestine
Strong bases (pKa >11) Ionized at all pH values
Poorly Absorbed from GIT
47. GIT motility and Gastric Emptying
• GI motility tends to move the drug through the
alimentary canal.
• For each drug there is an optimal absorption
window.
• Physiologic movement of drug within the GIT
depends on fed/fasted state.
• The time a dosage form takes to leave the
stomach is usually termed: the gastric
residence time, gastric emptying time.
48. • Rapid Gastric Emptying Advisable when :
– Rapid onset of action is desired eg. Sedatives
– Dissolution occurs in the intestine eg. Enteric coated tablets
– Drugs not stable in GI fluids eg. penicillin G
– Drug is best absorbed from small intestine eg. Vitamin B12
• Delay in Gastric Emptying recommended when
– Food promotes drug dissolution and absorption e.g.
Gresiofulvin
– Disintegration and dissolution is promoted by gastric fluids
49. Factors affecting Gastric Emptying
Volume of Ingested
Material
Bulky material tends to empty more slowly than
liquids
Type of Meal Gastric emptying rate:
carbohydrates > proteins > fats
Temperature of Food Increase in temperature, increase in emptying rate
Body Position Lying on the left side decreases emptying rate and right
side promotes it
GIT pH Retarded at low stomach pH and promoted at higher
alkaline pH
Emotional state Anxiety and stress promotes where as depression retards
it
Disease states gastric ulcer, diabetes and hypothyroidism retards it,
while duodenal ulcer, hyperthyroidism promotes it.
50. Effect of Food:
- The presence of food in the GIT can influence the rate
and extent of absorption, either directly or indirectly
via a range of mechanisms.
- As a general rule, drugs are better absorbed under
fasting conditions. Presence of food may retard or
prevent drug absorption.
- Generally the extent of absorption is not greatly
reduced. Occasionally absorption may be improved
- Food does not significantly influence absorption of a
drug taken half an hour or more before meals and two
hours or more after meals.
51. Effect of Food:
• Increased drug absorption following a meal
can be due to the following reasons:
a) Increased time for dissolution of poorly soluble drug.
b) Enhanced solubility due to GI secretions like bile.
c) Prolonged residence time and absorption site contact of
the drug e.g. water-soluble vitamins.
52. Effect of Food:
• Delayed or decrease drug absorption by food
can be due to one or more of the following
reasons:
a) Delayed gastric emptying, affecting the drugs unstable in the stomach
e.g. penicillin, erythromycin.
b) Preventing the transit of enteric tablets into the intestine which may be
as long as 6 – 8 hrs.
c) Formation of poorly soluble, unabsorbable complex e.g. tetracycline-
calcium complex.
d) Alteration of pH
e) Competition between food components and drugs for specialized
absorption mechanisms
53. Effect of Food:
• Types of meal
a) Meals high in fat aid solubilisation of poorly aqueous soluble
drugs like griseofulvin.
b) Food high in proteins increases oral availability of propranolol
because
such a meal promotes blood flow to the GIT helping in drug
absorption.
increases hepatic blood flow due to which the drug can bypass
first-pass hepatic metabolism (propranolol is a drug with high
hepatic metabolism)
55. A comparison of the effects of different types of food
intake on the serum griseofulvin levels following 1.0
g oral dose
56. Effect of water volume and meal on the
bioavailability of some drugs
F aspirin (650-mg) tablets,
erythromycin stearate (500-
mg) tablets, amoxicillin
(500-mg) capsules, and
theophylline (260-mg)
tablets, together with large
and small accompanying
volumes of water.
57. Theophylline serum concentrations in an
individual subject after a single 1500 mg Theo-24
Theophylline serum
concentrations in an individual
subject after a single 1500-mg
dose of Theo-24 taken during
fasting and after breakfast. The
shaded area indicates the
period during which this
patient experienced nausea,
repeated vomiting, or severe
throbbing headache. The
pattern of drug release during
the food regimen is consistent
with "dose dumping."