Chapter: 2

GASTRO-INTESTINAL ABSORPTION:
 Forces which help in transmembrane movements
Anatomical and physiological factors influencing absorption of drugs
Physicochemical properties of drugs affecting absorption
Absorption of different oral dosage forms
• INTRODUCTION
• It is defined as “the process of movement of
unchanged drug from the site of administration to
the systemic circulation”.
• There always present a correlation between plasma
concentration of a drug and the therapeutic
response thus, absorption can also be defined as
the “process of movement of unchanged drug from
the site of administration to the site of
measurement. i.e. plasma”.
• STRUCTURE OF CELL MEMBRANE
• Cell membrane separates living cell from nonliving surroundings.
• Thin barrier = 8 nm thick
• Controls traffic in and out of the cell
• Selectively permeable: allows some substances to cross more easily.
than others.
• Hydrophobic vs hydrophilic
• Made of phospholipids, proteins and other macromolecules.
• Proteins determine membrane’s specific functions.
• Cell membrane and organelle membranes each have unique collections
of proteins.
• Membrane proteins:
• Peripheral proteins
• Loosely bound to surface of membrane.
• Integral proteins:
• Penetrate lipid bilayer, usually across whole
membrane
• Transmembrane protein transport proteins
• Channels, permeases (pumps)
PHYSIOLOGICAL FACTORS AFFECTING ORAL ABSORPTION
• Passage of drugs across membrane.
1. Passive diffusion
2. Pore transport
3. Active transport
4. Facilitated diffusion
5. Pinocytosis
6. Ion pair formation
• MECHANISMS OF DRUG ABSORPTION
• PASSIVE DIFFUSION
• CHARACTERISTICS
• Diffusion
• Movement from high to low concentration.
• Major process for absorption of more than 90% of drugs.
• Non-ionic diffusion.
• Driving force: Concentration or electrochemical gradient.
• Difference in the drug concentration on either side of the
membrane.
• Drug movement is a result of kinetic energy of molecules.
FICK’S FIRST LAW OF DIFFUSION

· Expressed by Fick’s first law of diffusion:

- “The drug molecules diffuse from a region of higher concentration
to one of lower concentration until equilibrium is attained and the
rate of diffusion is directly proportional to the concentration
gradient across the membrane”.

dQ D A Km/w
= (CGIT__ CP )
dt h
• Where,
• dQ/dt = rate of drug diffusion (amount/time)
• D = diffusion coefficient of the drug
• A= surface area of the absorbing membrane for
drug diffusion
• Km/w = partition coefficient of drug between the
lipoidal membrane and the aqueous GI fluids
• h = thickness of the membrane
• (CGIT – Cp) = difference in the concentration of drug
in the GI fluids and the plasma (Concentration
Gradient)
• SINK CONDITION
• The passively absorbed drug enters blood, rapidly swept away and
distributed into a larger volume of body fluids.
• Hence, the concentration of drug at absorption site CGIT is
maintained greater than the concentration in the plasma.
Such a condition is called as sink condition for drug absorption.
• Under usual absorption conditions, D, A, Km/w and h are constants,
the term D A Km/w /h can be replaced by a combined constant P
called as permeability coefficient.
• Permeability: Ease with which a drug can permeate or diffuse
through a membrane.
• Due to sink conditions, the C is very small in comparison to CGIT.
dQ
= P CGIT
dt
2. PORE TRANSPORT
• Also known as convective transport, bulk flow or filtration.
• Important in the absorption of low mol. Wt. compounds. Low
molecular size (smaller than the diameter of the pore) and
generally water-soluble substances e.g. urea, water and sugars.
• The driving force for the passage of the drugs is the hydrostatic or
the osmotic pressure difference across the membrane.
• Mechanism – through the protein channel present in the cell
membrane.
• Drug permeation through pore transport – renal excretion,
removal of drug from CSF and entry of drug into the liver.
• Rate of absorption via pore transport depends on the number and
size of the pores, and given as follows:
dc NR2 A∆C
=
dt (η )(h)
• where,
- dc/ dt = rate of the absorption.
- N = number of pores
- R = radius of pores
- ∆C = concentration gradient
- η = viscosity of fluid in the pores
- h = thickness of the membrane
3. ION-PAIR TRANSPORT
• Responsible for absorption of compounds which ionizes at all pH values.
e.g. quaternary ammonium, sulphonic acids.
• Ion pair transport (IPT) is a process that increases the rate at which polar drugs can cross lipid membranes. It can
also improve the bioavailability of drugs that are hydrophilic and ionizable.
• How it works
• IPT occurs when oppositely charged ions are attracted to each other by electrostatic energy.
• The ions form a neutral complex that can be absorbed by the body.
• The neutral complex has the right amount of lipophilicity and aqueous solubility for passive diffusion.
• Applications
• IPT can be used to improve the bioavailability of drugs that are administered orally, parenterally, ocularly, or
transdermally.
• IPT can be used to increase the permeability of topically applied drugs.
• Ionized moieties forms neutral complexes with endogenous ions which have both the required lipophilicity
and aqueous solubility for passive diffusion.
• E.g. Propranolol, a basic drug that forms an ion pair with oleic acid and is absorbed by this mechanism.
4. IONIC OR ELECTROCHEMICAL DIFFUSION
• Charge on membrane influences the permeation of drugs.
• Molecular forms of solutes are unaffected by the membrane charge and
permeate faster than ionic forms.
• The permeation of anions and cations is also influenced by pH. Once
inside the membrane, the cations are attached to negatively charged
intracellular membrane, thus giving rise to an electrical gradient.
• If the same drug is moving from a higher to lower concentration, i.e.
moving down the electrical gradient, the phenomenon is known as
electrochemical diffusion.
• Thus, at a given pH, the rate of permeation may be as follows:
- Unionized molecule > anions > cations.
• CARRIER MEDIATED TRANSPORT
• Involves a carrier which reversibly binds to the
solute molecules and forms a solute-carrier
complex.
• This molecule transverse across the membrane to
the other side and dissociates, yielding the solute
molecule.
• The carrier then returns to the original site to
accept a new molecule.
• There are two type of carrier mediated transport
system.
• Facilitated diffusion - Active transport
I. FACILITATED DIFFUSION
• Facilitated diffusion is a form of carrier transport that
does not require the expenditure of cellular energy.
• Carriers are numerous in number and are found
dissolved in cell membrane.
• The driving force is concentration gradient, particles
move from a region of high conc. to low concentration.
• The transport is aided by integral membrane proteins.
• Facilitated diffusion mediates the absorption of some
simple sugars, steroids, amino acids and pyrimidines from the
small intestine and their subsequent transfer across cell
membranes.
II. ACTIVE TRANSPORT
• Active transport is the process of moving molecules across a cell membrane using energy from adenosine
triphosphate (ATP). This process is necessary for maintaining homeostasis in the cell.
• Energy source
• The energy for active transport comes from ATP, which is produced by the cell's metabolism.
• Direction
• Active transport moves molecules from a lower concentration to a higher concentration, against their
concentration gradient.
• Mechanisms
• Active transport uses pumps, which are transmembrane proteins that transport molecules across the
membrane.
• Types
• There are two types of active transport: primary and secondary.
• Examples
• The sodium-potassium pump and the sodium-dependent glucose cotransporter are examples of active
transport.
• Importance
• Active transport is essential for maintaining homeostasis in cells.
• It's important for transporting essential materials like water, hormones, and gases to and from cells, tissues,
• PRIMARY ACTIVE TRANSPORT
• Direct ATP requirement
• The process transfers only one ion or molecule and only in one
direction. Hence, called as uniport.
• E.g. Absorption of glucose.
• ABC (ATP Binding Cassette) transporters
• SECONDARY ACTIVE TRANSPORT
• No direct requirement of ATP
• The energy required in transporting an ion aids transport of
another ion or molecule (co-transport or coupled transport)
either in the same direction or opposite direction.
• 2 types:
• Symport (co-transport)
• Antiport (counter transport)
6. ENDOCYTOSIS
• It is a process in which cell absorbs molecules by engulfing them.
• Also termed as vesicular transport.
• It occurs by 3 mechanisms:
- Phagocytosis
- Pinocytosis
- Transcytosis
I. PHAGOCYTOSIS
• Phagocytosis refers to the engulfment of larger particles or
macromolecules, generally by macrophages.
II. PINOCYTOSIS
• It is a form of endocytosis in which small particles are brought to
the cell, forming an invagination.
• These small particles are suspended in small vesicles.
• It requires energy in the form of ATP.
• It works as phagocytosis, the only difference being, it is non-
specific in the substances it transports.
• This process is important in the absorption of oil soluble vitamins
& in the uptake of nutrients.
III. TRANSCYTOSIS
• It is the process through which various macromolecules are
transferred across the cell membrane.
• They are captured in vesicles, on one side of the cell and the
endocytic vesicle is transferred from one extracellular compartment to
another.
• Generally used for the transfer of IgA and insulin.
FACTORS AFFECTING DRUG ABSORPTION
1. Pharmaceutical factors
A. Physicochemical factors
B. Formulation factors
2. Patient related factors
A. Physiological factor
B. Clinical factor
1. PHARMACEUTICAL FACTORS
A. PHYSICO -CHEMICAL FACTORS
1. • Drug solubility and dissolution rate.
2. • Particle size & effective surface area.
3. • Polymorphism & amorphism.
4. • Salt form of the drug
5. • Lipophilicity of the drug
6. • pKa of the drug & pH
7. • Drug stability
I. DRUG SOLUBILITY AND DISSOLUTION RATE
• Rate determining process in the absorption of orally
administered drugs are:
- Rate of dissolution
- Rate of drug permeation through the bio-membrane.
• Hydrophobic: Rate Determination Step → Dissolution
- E.g: Griseofulvin, spironolactone
• Hydrophilic: Rate Determination Step → Permeation rate
limited.
- E.g: Cromolyn sodium or neomycin
II. PARTICLE SIZE AND EFFECTIVE SURFACE AREA
• Particle size and surface area of a solid drugs are inversely
related to each other.
• Hydrophobic drugs → micronization → greater surface area → rapid
dissolution.
• E.g: griseofulvin, spironolactone
• Some of the Hydrophobic drugs → micronization → decrease in
effective surface area → fall in dissolution rate.
• Causes
• Adsorption of air to surface
• Particle reaggregation
• Surface charge
• E.g: aspirin, phenacetin
• In that case add Surfactants: tween 80, hydrophilic diluents: PEG, PVP,
III. POLYMORPHISM AND AMORPHISM
• POLYMORPHISM
- A substance exists in more than one crystalline form, the
different forms are designated as polymorphs and the
phenomenon as polymorphism.
 Enantiotropic polymorph: Sulphur
 Monotropic polymorph: glyceryl stearate
- Depending on their relative stability, one of the several
polymorphic forms will be physically more stable than the
others.
- Stable polymorphs
 Highest MP
 Lowest energy state
 Least aqueous solubility
- Metastable polymorphs
 Low MP
 Higher energy state
 High aqueous solubility
- E.g. The vitamin riboflavin exists in several polymorphic
forms, and these have a 20-fold range in aqueous solubility.
• AMORPHISM
• These drugs can exist with no internal crystal structure.
• Such drug represents the highest energy state and can be
considered as super cooled liquids and thus have greater
solubility. E.g. Novobiocin.
-Thus, the order of dissolution and hence absorption for
different solid dosage forms is amorphous > meta-stable >
stable.
• SALT FORM OF THE DRUG
• Salt of weak acid and weak bases have much higher
aqueous solubility than the free acid or base.
• Therefore, if the drug can be given as a salt, the solubility
can be increased, and the dissolution thus can be improved.
V. DRUG pKa, LIPOPHILICITY AND GI pH
pH PARTITION THEORY
• Explains influences of GI pH, drug pKa on the extent of drug transfer or
drug absorption (Ka – absorption rate constant).
• The process of absorption of drug compounds of molecular weight greater
than 100 Daltons transported across the bio-membrane by passive diffusion
depend upon the following factors:
- Dissociation constant of the drug i.e. pKa of the drug
- Lipid solubility of the unionized drug i.e. Ko/w
- pH at the absorption site
- Dissociation or ionization constant:
 pH at which half of the substance is ionized and half is unionized.
• pH of medium
- Affects ionization of drugs:
 Weak acids → best absorbed in stomach.
 Weak bases → best absorbed in intestine.
• pH-partition Hypothesis
- Unionized Drug: Higher Absorption
- Ionized Drug: Low Absorption
• FOR WEAK ACIDS
10 pH - pKa
% Drug Ionized = X 100
1 + 10pH - pKa
• FOR WEAK BASES

10pKa − pH
% DrugIonized = X 100
1 + 10pKa − pH
PREDICTION BASED ON THEORY
Drugs PKa PH / Site of absorption
For Acidic Drugs
Very weak acids Unionized at all pH values;
E.g. pentobarbital, >8 Absorbed along the entire
Hexobarbital length of GIT.

Moderately weak acids Unionized in gastric pH and ionized

E.g. aspirin, Ibuprofen 2.5 – 7.5 in intestinal pH; better
absorption from stomach.

Stronger acids Ionized at all pH values; Poorly

E.g. disodium < 2.0 absorbed from GIT.
Cromoglycate

For Basic Drugs

Very weak bases Unionized at all pH values;
E.g. theophylline, < 5.0 Absorbed along entire GIT.
Caffeine

Ionized at gastric pH, unionized

Moderately weak bases 5 – 11 at intestinal pH; better
E.g. codeine absorption from intestine.

Stronger bases > 11 Ionized at all pH values; Poorly

E.g. guanethidine absorbed from GIT.
VI. LIPOPHILICITY
• Only unionized drug having sufficient lipid
solubility are absorbed into systemic circulation.
• So, drug should have sufficient aqueous solubility to dissolve in
the fluids at the absorption site and lipid solubility high enough to
facilitate the partitioning of the drug in lipoidal membrane and into
systemic circulation.
VII. DRUG PERMEABILITY
• Three major drug properties which affects drug permeability:
- Lipophilicity
- Polarity of the drug
- Molecular size of the drug
VIII. DRUG STABILITY
• Two major stability problems are:
- Degradation of the drug into inactive form.
- Interaction with one or more component either of the dosage form or those
present in the GIT to form a complex that is poorly soluble.
B. FORMULATION FACTORS
• Disintegration time
• Manufacturing variables
• Different Oral Dosage forms
• Pharmaceutical ingredients/ Excipients
• Product age and storage condition
I. DISINTEGRATION TIME (to undue the integrity/break into parts)
• It Is of particular importance in case of solid dosage forms like tablets and
capsules.
• Rapid disintegration is important in the therapeutic success of solid
dosage form.
• Sugar coated tablets have long disintegration time (DT).
• DT is directly related to the amount of binder present and the
compression force of a tablet.
• After disintegration, granules deaggregate into tiny particles →
dissolution faster.
II. MANUFACTURING VARIABLES
a) METHOD OF GRANULATION
• Wet granulation was thought to be the most conventional technique.
• Direct compressed tablets dissolve faster
b) COMPRESSION FORCE
• Higher compression force → increased density and hardness →
decreased porosity and penetrability → reduced wettability → in turn
decreased DR.
• Also causes deformation
c) INTENSITY OF PACKING OF CAPSULE CONTENTS
• Tightly filled capsules-diffusion of GI fluids → high pressure →
rapid bursting and dissolution of contents.
• Opposite also possible → Poor drug release due to decreased
pore size and poor penetrability of GI fluids.
III. ABSORPTION OF DIFFERENT ORAL DOSAGE FORMS
• Different Types
- Solution
- Suspension
- Tablets
- Capsules
- Enteric Coated Tablet
- Powders
• Order of absorption
Solutions > Emulsions > Suspensions > Capsules > Tablets > Coated
Tablets > Enteric Coated Tablet > Sustain Release Tablet
a) SOLUTION
• Aqueous solutions, syrups, elixirs, and emulsions do not present
a dissolution problem and generally result in fast and often complete
absorption as compared to solid dosage forms.
b) SOLID SOLUTIONS
• The solid solution is a formulation in which drug is trapped as a solid
solution or monomolecular dispersion in a water-soluble matrix. Although the
solid solution is an attractive approach to increase drug absorption, only one drug,
griseofulvin, is currently marketed in this form.
OR
A solid solution dosage form is a type of pharmaceutical formulation where a drug
is dissolved in a solid carrier material, typically a polymer or a wax, at the
molecular or atomic level.
Characteristics:
1. Uniform distribution: The drug is evenly distributed throughout the solid carrier.
2. Molecular dispersion: The drug is dissolved at the molecular level, resulting in a
homogeneous mixture.
3. Solid-state: The dosage form is a solid, rather than a liquid or semi-solid.
4. Improved bioavailability: Solid solutions can enhance the solubility and
bioavailability of poorly soluble drugs.
Types of solid solutions:
5. Molecular dispersions: The drug is dispersed at the molecular level in a polymer
or wax.
6. Amorphous solid dispersions: The drug is dispersed in an amorphous polymer,
which can improve solubility and bioavailability.
7. Eutectic mixtures: A mixture of two or more substances that form a eutectic
mixture, which has a lower melting point than the individual components.
Advantages:
Improved bioavailability
Enhanced solubility
Increased stability
Better patient compliance due to improved taste and texture
Examples of solid solution dosage forms:
1. Tablets
2. Capsules
3. Powders
4. Granules
c) SUSPENSIONS
• A drug in a suspension is in solid form but is finely divided and has a
large surface area. Drug particles can diffuse readily between the stomach
and small intestine so that absorption is relatively insensitive to stomach
emptying rate.
• Adjusting the dose to a patient’s needs is easier with solutions and
suspensions than with solid dosage forms. Liquid dosage forms, therefore,
have several practical advantages besides simple dissolution rate.
• However, they also have some disadvantages, including greater bulk,
difficulty in handling, and perhaps reduced stability.
d) TABLETS AND CAPSULES
• These formulations differ from each other in that material in
capsules is less impacted than in compressed tablets. Once a capsule
dissolve, the contents generally disperse quickly. The capsule material,
although water soluble, can impede drug dissolution by interacting with
the drug, but this is uncommon.
• Tablets generally disintegrate in stages, first into granules and
then into primary particles. As particle size decreases, dissolution rate
increases due to increased surface area.
IV. PHARMACEUTICAL INGREDIENTS/EXCIPIENTS
• More the number of excipients in dosage form, more complex it is and
greater the potential for absorption and bioavailability problems.
• Changing an excipient from calcium sulfate to lactose and increasing
the proportion of magnesium silicate, increases the activity of oral phenytoin.
• Absorption of tetracycline from capsules is reduced by calcium
phosphate due to complexation.
• Most of these types of interactions were reported some time ago and
are unlikely to occur in the current environment of rigorous testing of new
dosage forms and formulations.
• Excipients commonly used:
- Vehicle
- Diluents
- Binders & granulating agent
- Disintegrants
- Lubricants
- Suspending agents/viscosity agent
- Surfactants
- Bile salts
- Colorants
V. PRODUCT AGE AND STORAGE CONDITIONS
• Aging and alteration in storage condition changes the physiochemical
properties of a drug which adversely affects bioavailability.
• During storage
- Metastable form → Stable form
- Change in particle size
- Tablet → harden / soften
• E.g.
- Prednisone tablet containing lactose as a filler, high temp and high
humidity resulted in harder tablet that disintegrated and dissolve slowly.
2. PATIENT RELATED FACTORS
A. PHYSIOLOGIC FACTORS RELATED TO DRUG ABSORPTION
I. MEMBRANE PHYSIOLOGY
• Nature of Cell Membrane
• Transport Processes
II. GASTERO-INTESTINAL PHYSIOLOGY
a) GASTRIC EMPTYING RATE
• Anatomically, a swallowed drug rapidly reaches the stomach.
• Eventually, the stomach empties its contents into the small
intestine. Because the duodenum has the greatest capacity for the
absorption of drugs from the GI tract, a delay in the gastric emptying time
for the drug to reach the duodenum will slow the rate and possibly the
extent of drug absorption, thereby prolonging the onset time for the drug.
• Some drugs, such as penicillin, are unstable in acid and
decompose if stomach emptying is delayed. Other drugs, such as aspirin,
may irritate the gastric mucosa during prolonged contact.
• Gastric emptying rate is faster in case of solution & suspensions
than solid and non-disintegrating dosage forms.
• Factors that influence gastric emptying rate are:
- Volume of meal
- Composition of meal
- Physical state and viscosity of meal
- Temperature of meal
- Gastrointestinal pH
- Electrolyte and osmotic pressure
- Body posture
- Emotional state
b) INTESTINAL MOTILITY
• Normal peristaltic movements mix the contents of the
duodenum, bringing the drug particles into intimate contact with the
intestinal mucosal cells.
• The drug must have a sufficient time (residence time) at the
absorption site for optimum absorption. In the case of high motility in
the intestinal tract, as in diarrhea, the drug has a very brief residence
time and less opportunity for adequate absorption.
c) DRUG STABILITY IN GIT
• Metabolism or degradation by enzymes or chemical hydrolysis may adversely
affect the drug absorption and thus reduces bioavailability.
• Destruction in gastric acid.
• Generally, a problem with orally administered drugs.
d) INTESTINAL TRANSIT
• Long intestinal transit time is desirable for complete absorption of drug
e.g. for enteric coated formulation and for drugs absorbed from specific sites in the
intestine.
• Peristaltic contraction promotes drug absorption by increasing the drug
membrane contact and by enhancing dissolution especially of poorly soluble drugs.
• Influenced by food, disease and drugs. e.g. metoclopramide which promotes
intestinal transit and thus enhance absorption of rapidly soluble drugs while
anticholinergic retards intestinal transit and promotes the absorption of poorly
soluble drugs.
e) BLOOD FLOW TO GIT
• Once the drug is absorbed from the small intestine, it enters via the
mesenteric vessels to the hepatic-portal vein and the liver prior to reaching the
systemic circulation. Any decrease in mesenteric blood flow, as in the case of
congestive heart failure, will decrease the rate of drug removal from the intestinal
tract, thereby reducing the rate of drug bioavailability.
• GIT has higher perfusion rate because it is extensively supplied by blood
capillary network.
• Therefore, help in maintaining sink conditions and concentration gradient for
drug absorption by rapidly removing of drug from site of action.
• Blood flow is important for actively absorption of drugs.
• Highly permeable drugs or drugs that absorbed through pores –GI perfusion
is rate limiting while the drugs with poor permeability GI perfusion is not important.
• Perfusion increases after meals and persist for few hours, but absorption is
not affected.
f) EFFECT OF FOOD
• The presence of food in the GI tract can affect the bioavailability of the drug
from an oral drug product.
• Digested foods contain amino acids, fatty acids, and many nutrients that may
affect intestinal pH and solubility of drugs. The effects of food are not always
predictable and can have clinically significant consequences. Some effects of food on
the bioavailability of a drug from a drug product include:
- Delay in gastric emptying
- Stimulation of bile flow
- A change in the pH of GI tract
- An increase in splanchnic blood flow
- A changed luminal metabolism of the drug substance
- Physical or chemical interaction of the meal with the drug product or drug
substance.
• The absorption of some antibiotics, such as penicillin and
tetracycline, is decreased with food, whereas other drugs, particularly
lipid-soluble drugs such as griseofulvin and metaxalone, are better
absorbed when given with food containing a high fat content.
• Propranolol plasma concentrations are larger after food than in
fasted subjects. This may be an interaction with the components of
food.
III. AGE
• In infants, the gastric pH is high and intestinal surface and blood
flow to the GIT is low resulting in altered absorption pattern in
comparison to adults.
• In elderly persons, causes of impaired drug absorption include
altered gastric emptying, decreased intestinal surface area and GI blood
flow and bacterial overgrowth in small intestine.
B. CLINICAL FACTORS
I. DISEASE STATE
• Several disease state may influence the rate and extent of drug
absorption.
• Three major classes of disease may influence bioavailability of
drug.
- GI diseases
- CVS diseases
- Hepatic diseases
a) GI DISEASES
• GI Infections
- Celiac disease: Characterized by destruction of villi and microvilli.
Abnormalities associated with this disease are increased gastric emptying rate
and GI permeability, altered intestinal drug metabolism.
• Crohn’s disease
- Altered gut transit time and decreased gut surface area and intestinal
transit rate.
• GI surgery
- Gastrectomy may cause drug dumping in intestine, osmotic diarrhea and
reduce intestinal transit time.
b) CVS DISEASES
• In CVS diseases blood flow to GIT decrease causing decreased
drug absorption.
c) HEPATIC DISEASES
• Disorders like hepatic cirrhosis influences bioavailability of drugs
which undergoes first pass metabolism.
II. DRUGS
a) ANTICHOLINERGIC
• Anticholinergic drugs in general may reduce stomach acid secretion
Propantheline bromide is an anticholinergic drug that may slow stomach
emptying and motility of the small intestine. Slower stomach emptying may
cause delay in drug absorption
b) METOCLOPRAMIDE
• Metoclopramide is a drug that stimulates stomach contraction,
relaxes the pyloric sphincter, and, in general, increases intestinal peristalsis,
which may reduce the effective time for the absorption of some drugs.
c) ANTACIDS
• Antacids containing aluminum, calcium, or magnesium may
complex with drugs such as tetracycline, ciprofloxacin, and indinavir,
resulting in a decrease in drug absorption.
The end……