Amity Institute of Pharmacy

Factors Affecting Drug

Absorption

Made By :-
Jatin Rathee
M.Pharm
Pharmaceutics
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Absorption Of Drugs
 A drug injected intravascularly (intravenously and/or intra
arterially) directly enters the systemic circulation and exerts its
pharmacological effects. However, a majority of drugs are
administered extravascularly, generally orally.
 Drug absorption is defined as the process of movement of
unchanged drug from the site of administration to systemic
circulation.
 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.

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Factors Affecting Drug Absorption

 Biopharmaceutic considerations in dosage form design :-
 To achieve the desired therapeutic objective, the drug product
must deliver the active drug at an optimal rate and amount.
 By proper biopharmaceutic design, the rate and extent of
absorption or the systemic delivery of drug to the body can be
varied from rapid and complete absorption to slow and sustained
absorption depending upon the desired therapeutic objective.
 The process consists of 4 steps :-
1. Disintegration of the drug product.
2. Deaggregation and subsequent release of the drug.
3. Dissolution of the drug in the aqueous fluids at the absorption
site.
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4. Absorption.
 In a series of kinetic or rate processes, the rate at which the drug
reaches the systemic circulation is determined by the slowest of
the various steps involved in the sequence. Such a step is called
as the rate determining or rate limiting step (RDS).
 Factors influencing are :-
1. Pharmaceutical factors.
2. Patient related factors.

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Pharmaceutical Factors
 In order to design a formulation that will deliver the drug in the most
bioavailable form, the pharmacist must consider :-
1. Physicochemical properties of the drug.
2. Types of formulation (eg., solution, suspension, tablet etc.)
3. Nature of excipients in the formulation.
1. Physicochemical properties of the drug :-
 Drug solubility and dissolution rate.
 Particle size and effective surface area.
 Polymorphism and amorphism.
 Pseudopolymorphism (hydrates/solvates).
 Salt form of the drug.
 Lipophilicity of the drug.

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 pKa of the drug and gastrointestinal pH.

 Drug stability.
 Stereochemical nature of the drug.

2. Dosage form characteristics and pharmaceutical ingredients

(Pharmaco-technical factors) :-
 Disintegration time (tablets/capsules).
 Dissolution time.
 Manufacturing variables.
 Pharmaceutical ingredients (excipients/adjuvants).
 Nature and type of dosage form.
 Product age and storage conditions.

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Physicochemical Factors
1. Drug solubility and Dissolution rate :-
 The two critical slower rate determining processes in the
absorption of orally administered drugs are :-
1. Rate of dissolution.
2. Rate of drug permeation through the biomembrane.
 Dissolution is the rate determining step for hydrophobic, poorly
aqueous soluble drugs like griseofulvin and spironolactone;
absorption of such drugs is said to be dissolution rate limited.
 If the drug is hydrophilic with high aqueous solubility, for eg. :-
cromolyn sodium or neomycin, then dissolution is rapid and the
rate determining step in the absorption of such drugs is rate of
permeation through the biomembrane; absorption of such drugs
is said to be permeation rate limited or transmembrane rate
limited.
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 Based on the intestinal permeability and solubility of drugs, Amidon

et al developed Biopharmaceutics Classification System (BCS) :-
Class Solubilit Permeability Absorption Rate limiting Examples
y Pattern step in
absorption
I High High Well Gastric Diltiazem
absorbed emptying
II Low High Variable Dissolution Nifedipine
III High Low Variable Permeability Insulin
IV Low Low Poorly Case by case Taxol
absorbed
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 An important prerequisite for the absorption of drug by all

mechanisms except endocytosis is that it must be present in
aqueous solution. This in turn depends on the drug’s aqueous
solubility and its dissolution rate.
 Absolute or intrinsic solubility is defined as the maximum amount
of solute dissolved in a given solvent under standard conditions of
temperature, pressure and pH. It is a static property.
 Dissolution rate is defined as the amount of solid substance that
goes into solution per unit time under standard conditions of
temperature, pH, solvent composition and constant solid surface
area. It is a dynamic process.
 Several drugs have poor aqueous solubility to have a bearing on
dissolution rate. The matter is of great concern when the solubility
is less than 1 to 2 mg/ml in the pH range of 2 to 8.

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 However, there are well known examples of drugs such as

cisapride which despite their low aqueous solubility have sufficient
oral bioavailability.
 Two reasons can be attributed to this :- one, the rapid rate of
dissolution despite low intrinsic solubility and two, the therapeutic
dose of drug may be so small that the GI transit time is sufficient
for adequate dissolution and absorption to occur.
 Thus, in contrast to absolute solubility, the dynamic process of
drug dissolution is better related to drug absorption and
bioavailability.
2. Particle size and effective surface area of the drug :-
 Particle size and surface area of solid drug are inversely related to
each other.
 Smaller the drug particle, greater the surface area.

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 Two types of surface area of interest can be defined :-

1. Absolute surface area :- It is the total area of solid surface of any
particle.
2. Effective surface area :- It is the area of solid surface exposed to
the dissolution medium.
 In absorption studies, the effective surface area is of more
important than absolute.
 Particle size reduction has been used to increase the absorption
of large number of poorly soluble drugs. Eg. :- Bishydroxy-
coumarin, digoxin and griseofulvin.
 To increase the effective surface area, we have to reduce the
particle size of particles upto 0.1 micron. So, these can be
achieved by microionisation process.

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 But in these case one most important thing to be keep in mind

that which type of drug is microionised if it is :-
1. Hydrophilic drugs :-
 In hydrophilic drugs, the smaller particles have higher energy than
the bulk of the solid resulting in an increased interaction with the
solvent.
 Eg. :-
1. Griseofulvin :- dose reduced to half due to microionisation.
2. Spironolactone :- the dose was decreased to 20 times.
 After microionisation, it was found that the absorption efficiency
was highly increased.
2. Hydrophobic drugs :-
 In this microionisation techniques results in decreased effective
surface area and thus fall in dissolution rate.

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 Reasons :-
1. The hydrophobic surface of the drugs absorbs air onto their
surface which inhibits their wettability.
2. The particle reaggregates to form large particles due to their high
surface free energy, which either float on the surface or settle on
the bottom of the dissolution medium.
3. Electrically induced agglomeration owing to surface charges
prevents intimate contact of the drug with the dissolution
medium.
 Such hydrophobic drugs can be converted to their effective
surface area :-
1. Use of surfactant as a wetting agent :-
 decrease the interfacial tension.
 displace the absorbed air with the solvent. Eg. :- Phenacetin.
2. Add hydrophilic diluents like PEG, PVP, dextrose etc. which coat
the surface of hydrophobic drug particles.

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3. Polymorphism and Amorphism :-

 Depending upon the internal structure, a solid can exist either in a
crystalline or amorphous form.
 When a substance exists in more than one crystalline form, the
different forms are designated as polymorphs and the
phenomenon as polymorphism.
 Polymorphs are of 2 types :-
1. Enantiotropic polymorph :- This is the one which can be
reversibly changed into another form by altering the temperature
or pressure. Eg. :- Sulphur.
2. Monotropic polymorph :- This the one which is unstable at all
temperatures and pressures. Eg. :- Glyceryl stearates.
 The polymorphs differ from each other with respect to their
physical properties such as solubility, melting point, density,
hardness and compression characteristics. Thus, these change in
physical properties affect the dissolution properties and hence the
absorption.
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 Eg. :- Vitamin riboflavin exists in several polymorphic forms,

polymorphic form III of riboflavin is 20 times more water soluble
than the form I.
 Amorphism :-
 Some drugs can exist in amorphous form (i.e. having no internal
crystal structure). Such drugs represent the higher energy state
and can be considered as supercooled liquids.
 They have greater aqueous solubility than the crystalline forms
because the energy required to transfer a molecule from crystal
lattice is greater than that required for non crystalline (amorphous
form).
 Eg. :- The amorphous form of novobiocin is 10 times more soluble
than the crystalline form.
 Thus, the order of dissolution of different solid forms of drugs
like :-
Amorphous > Metastable > Stable

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4. Hydrates/Solvates (Pseudopolymorphism) :-
 The crystalline form of drug can either be a polymorph or a molecular
adduct or both.
 The stoichiometric type of adducts where the solvent molecules are
incorporated in the crystal lattice of the solid are called as solvates, and
the trapped solvent as solvent of crystallization.
 The solvates can exist in different crystalline forms called as
pseudopolymorphs. The phenomenon is called as pseudopolymorphism.
 When the solvent in association with the drug is water, the solvate is
known as a hydrate. Hydrates are most common solvate forms of drugs.
 Generally, the amorphous form of a drug has greater aqueous solubility.
 Hydrates/Solvates are pseudopolymorphs where hydrates are less
soluble and solvates are more soluble and thus affect the absorption
accordingly.
 For example :- n-pentanol solvates of fludrocortisone and succinyl-
sulphathiazole have greater aqueous solubility than the non solvates.

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5. Salt form of drug :-

 While considering the salt form of drug, pH of the diffusion layer is more
important not the pH of the bulk of the solution.
 Most drugs are either weak acids or weak bases. One of the easiest
approaches to enhance the solubility and dissolution rate of the drugs is
to convert them into their salt forms.
 Example of salt of weak acid :- It increases the pH of the diffusion layer,
which promotes the solubility and dissolution of a weak acid and
absorption is bound to be rapid.
 Other approach to enhance the dissolution and absorption rate of certain
drugs is the formation of in situ formation i.e. increasing in pH of
microenvironment of drug by incorporation of a buffering agent. Eg. :-
aspirin, penicillin.
 But sometimes more soluble salt form of drug may result in poor
absorption. Eg. :- Sodium salt of phenobarbitone viz, its tablet swells and
did not disintegrate, thus dissolved slowly and results in poor absorption.

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6. Drug pKa and lipophilicity and gastrointestinal pH – pH partition

hypothesis :-
 The pH partition hypothesis theory (Brodie et al) explains in
simple terms, the process of drug absorption from the GIT and its
distribution across all biological membranes.
 The theory states that for drug compounds of molecular weight
greater than 100, which are primarily transported across the
biomembrane by passive diffusion, the process of absorption is
governed by :-
1. The dissociation constant (pKa) of the drug.
2. The lipid solubility of the unionized drug.
3. The pH at the absorption site.
1. Drug pKa and gastrointestinal pH :-
 The amount of drug that exists in unionized form is a function of
dissociation constant (pKa) of the drug and pH of the fluid at the
absorption site.

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 It can be determined by Henderson – Hasselbalch equations :-

For weak acids;

For weak bases;

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 If there is a membrane barrier that separates the aqueous

solutions of different pH such as GIT and the plasma, then the
theoretical ratio R of drug concentration on either side of the
membrane can be given by equations derived by Shore et al :-
For weak acids;

For weak bases;

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2. Lipophilicity and drug absorption :-

 As mentioned earlier, it is the pKa of the drug that determines the
degree of ionization at a particular pH and that only the unionized
drug, if sufficiently lipid soluble, is absorbed into the systemic
circulation. Thus, even if the drug exists in the unionised form, it
will be poorly absorbed if it has poor lipid solubility (or low Ko/w).
 Ideally, for optimum absorption, a drug should have sufficient
aqueous solubility to dissolve in the fluids at the absorption site
and lipid solubility (Ko/w) high enough to facilitate the partitioning
of the drug in the lipoidal biomembrane and into the systemic
circulation.
 In other words, a perfect hydrophilic lipophilic balance (HLB)
should be there in the structure of the drug for optimum
bioavailability.
 The lipid solubility of a drug is measured by a parameter called as
log P where P is oil/water partition coefficient (Ko/w) value of the
drug.
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For acidic drugs;

For basic drugs;

 Limitations of pH partition hypothesis :-

1. Presence of virtual membrane pH :-
 The pH partition hypothesis suggested that only the unionised drug at a
given GI lumen pH is absorbed.]
 An S shaped curve called as pH absorption curve denoting the
dissociation of drug.

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 However, differences in the extent of absorption of salicylic acid

have been observed at a given GI pH than that predicted by pH
partition hypothesis.
 The experimental pH absorption curves are less steep and shift to
the left (lower pH values) for a basic drug and to the right (higher
pH values) for an acidic drug.
 This led to the suggestion that a virtual pH, also called as the
microclimate pH, different from the luminal pH exists at the
membrane surface.
2. Absorption of ionized drugs :-
 An important assumption of the theory was that only unionized
form of the drug is absorbed and permeation of the ionized drug is
negligible since its rate of absorption is 3 to 4 times less than that
of unionized drug. This is called as principle of non ionic diffusion.

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 However, the pH absorption curve shift suggested that ionized forms of

some drugs also get absorbed to a considerable extent.
3. Influence of GI surface area and residence time of drug :-
 According to the pH partition theory, acidic drugs are best absorbed from
stomach and basic drugs from intestine in which conditions they are
unionized to a large extent. This could be under conditions where the
surface area of stomach and intestine are same.
 But irrespective of the GI pH and the degree of ionization, both acidic and
basic drugs are more rapidly absorbed from intestine, primarily because of
its large surface area and secondly, because of long residence time of drug
in the intestine.
4. Presence of aqueous unstirred diffusion layer :-
 The pH shift in the absorption of acidic and basic drugs, also accounts for
the fact that the bulk of the luminal fluid is not in direct contact with the
membrane but a barrier called as aqueous unstirred diffusion layer is
interposed between them.
 Such a layer has a real thickness and is a barrier to absorption of drugs.

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7. Drug stability :-
 A drug for oral use may destabilize either during its shelf life or in
the GIT.
 Two major stability problems resulting in poor bioavailability of an
orally administered drug are – degradation of the drug into
inactive form and interaction with one or more different component
either of the dosage form or those present in the GIT to form a
complex that is poorly soluble or is unabsorbable.
8. Stereochemical nature of drug :-
 Chiral drugs constitute approximately 60% of the drugs in current
use. Majority of these are marketed as racemic mixtures.
 Although it is well established that optical isomers differ in the
potency of pharmacological effect, it is only recently that attention
is being paid to influence of chirality on pharmacokinetic
processes like absorption, distribution and elimination.

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Dosage form characteristics and Pharmaceutical

ingredients (Pharmacotechnical factors)
1. Disintegration time (tablets/capsules) :-
 Rapid disintegration is important to have a rapid absorption so
lower disintegration time is required.
 Disintegration time of tablet is directly proportional to amount of
binder and compression force.
 In vitro disintegration test gives no means of a guarantee of drugs
bioavailability because if the disintegrated drug particles do not
dissolve then absorption is not possible.
 Eg. :- Coated tablets have long disintegration time and fast
dispersible tablets have short disintegration time.
2. Dissolution time :-
 Dissolution is a process in which a solid substance solubilises in a
given solvent i.e. mass transfer from the solid surface to the liquid
phase.
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 Dissolution time is also an important factor which affect the drug

absorption.
3. Manufacturing variables :-
 Several manufacturing processes influence drug dissolution from
solid dosage forms.
 For example :- For tablet it is
1. Method of granulation :-
 The wet granulation process is the most conventional technique.
 The tablets that dissolve faster than those made by other
granulation methods.
 But wet granulation has several limitations like formation of crystal
bridge or chemical degradation.
 The method of direct compression force has been utilized to yield
the tablets that dissolve at a faster rate.

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2. Compression force :-
 The compression force employed in tableting process influence density,
porosity, hardness, disintegration time and dissolution of tablets.
 Higher compression force increases the density and hardness of tablet,
decreases porosity and hence penetrability of the solvent in the tablet and
thus results in slowing of dissolution and absorption.
 On the other hand, higher compression forces cause deformation,
crushing or fracture of drug particles into smaller ones or convert a
spherical granule into a disc shaped particle with a large increase in the
effective surface area.
 A combination of both the curves A and B is also possible as shown in
curves C and D.

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4. Pharmaceutical ingredients (excipients/adjuvants) :-

 Commonly used excipients in various dosage forms are :-
1. Vehicle :-
 Rate of absorption depends on its miscibility with biological fluid.
 Miscible vehicles causes rapid absorption. Eg. :- PEG.
 In immiscible vehicles, the absorption depends on its partitioning
from oil phase to aqueous body fluid.
2. Diluents :-
 Hydrophilic diluents imparts absorption and hydrophobic diluents
retards absorption.
 Also, there is a drug diluent interaction, forming insoluble complex
and retards the absorption. Eg. :- Tetracycline – DCP.
3. Binders and granulating agents :-
 Hydrophilic binders imparts hydrophilic properties to the granule
surface and gives better dissolution properties. Eg. :- Starch,
Gelatin and PVP.

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 More amount of binder increases the hardness of the tablet and

retards the absorption rate.
4. Disintegrants :-
 Mostly hydrophilic in nature.
 Decrease in amount of disintegrants, significantly lowers
bioavailability.
5. Lubricants :-
 Commonly hydrophobic in nature and therefore inhibits
penetration of water into tablet and thus dissolution and
disintegration.
6. Suspending agents/viscosity agents :-
 Stabilized the solid drug particles and thus affect drug absorption.
 Macromolecular gum forms an unabsorbable complex with drug.
Eg. :- Sodium CMC.
 Viscosity imparters act as a mechanical barrier to diffusion of drug
from its dosage form and retard GI transit of drug.

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7. Surfactants :-
 May enhance or retards drug absorption by interacting with drug or
membrane or both. Eg. :- Griseofulvin, steroids.
 It may decrease absorption when it forms the unabsorbable complex with
drug above CMC.
8. Coating :-
 In general, deleterious effects of various coatings on the drug dissolution
from a tablet dosage form are in the following order :-
Enteric coat > sugar coat > non enteric coat
 The dissolution profile of certain coating materials change on aging. Eg. :-
shellac coated tablets, on prolonged storage, dissolve more slowly in the
intestine. This can be however, be prevented by incorporating little PVP in
the coating formulation.
9. Buffers :-
 Buffers are sometimes useful in creating the right atmosphere for drug
dissolution as was observed for buffered aspirin tablets.

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 However, certain buffer systems containing potassium cations inhibit the

drug absorption as seen with vitamin B2 and sulfanilamide.
10. Colorants :-
 Even a low concentration of water soluble dye can have an inhibitory
effect on dissolution rate.
 The dye molecules get absorbed onto the crystal faces and inhibit the
drug dissolution.
 For example :- Brilliant blue retards dissolution of sulfathiazole.
11. Complexing agents :-
 Complex formation has been used to alter the physicochemical and
biopharmaceutical properties of a drug.
 For example :-
1. Enhanced dissolution through formation of a soluble complex. Eg. :-
Ergotamine tartarate caffeine complex.
2. Enhanced lipophilicity for better membrane permeability. Eg. :- Caffeine
– PABA complex.

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5. Nature and type of dosage form :-

 Apart from the proper selection of the drug, clinical success often
depends to a great extent on the proper selection of the dosage form of
that drug.
 As a general rule, the bioavailability of a drug form various dosage forms
decrease in the following order :-
Solutions > emulsions > suspensions > capsules > tablets > coated tablets >
enteric coated tablets > sustained release products.
6. Product age and storage conditions :-
 Product aging and storage conditions can adversely affect the
bioavailability by change in especially the physicochemical properties of
the dosage forms.
 For example :-
1. Precipitation of the drug in solution.
2. Hardening of tablet.
3. Change in particle size of suspension.

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Patient related factors

 It includes factor relating to the anatomical, physiological and
pathological characteristics of the patient.
1. Age.
2. Gastric emptying time.
3. Intestinal transit time.
4. Gastrointestinal pH.
5. Disease states.
6. Blood flow through the GIT.
7. Gastrointestinal contents.
8. Contact time with gastrointestinal mucosa.
9. Presystemic metabolism.

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1. 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, higher incidents of achlorhydria and bacterial
overgrowth in small intestine.
2. Gastric emptying time :-
 The process by which food leaves the stomach and enters the
duodenum.
 Rapid gastric emptying is required when the drug is best
absorbed from distal part of the small intestine.
 Delayed gastric emptying is required when drugs are absorbed
from proximal part of the small intestine and prolonged drug
absorption site contact is desired.
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 Gastric emptying is a first order process.

 Several parameters are used to quantify gastric emptying :-
1. Gastric emptying rate :- It is the speed at which the stomach contents
empty into the intestine.
2. Gastric emptying time :- It is the time required for the gastric contents to
empty into the small intestine.
3. Gastric emptying half life :- It is the time taken for half the stomach
contents to empty.
3. Intestinal transit time :-
 Intestinal transit time is the major site of absorption of most of the drugs.
 Intestinal transit time is influenced by various factors such as food,
diseases and drugs.
 Eg. :- Metoclopramide which promotes intestinal transit, enhance
absorption of rapidly soluble drugs while anticholinergic retards intestinal
transit and promotes the absorption of poorly soluble drugs.

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Intestinal region Transit time

Duodenum 5 minutes
Jejunum 2 hours
Ileum 3 to 6 hours
Caecum 0.5 to 1 hour
Colon 6 to 12 hours

4. Gastrointestinal pH :-
 The GI pH generally increases gradually as one move down the
stomach to the colon and rectum.
 GI fluid pH influence drug absorption in several ways :-
1. Disintegration :-
 The disintegration of some dosage forms is pH sensitive.
 With enteric coated formulations, the coat dissolves only in the
intestine followed by disintegration of the tablet.

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2. Dissolution :-
 A large number of drugs are either weak acids or weak bases whose
solubility is greatly affected by pH.
 A pH that favours formation of salt of the drug enhances the dissolution
of that drug.
3. Absorption :-
 Depending upon the drug pKa and whether its an acidic or a basic drug,
the GI pH influences drug absorption by determining the amount of drug
that would exist in the unionized form at the site of absorption.
4. Stability :-
 GI pH also influences the chemical stability of drugs.
 The acidic stomach pH is known to affect degradation of penicillin G and
erythromycin.
 This can be overcome by preparing prodrugs of such drugs that do not
degrade or dissolve in acidic pH. Eg. :- Carindacillin, erythromycin
estolate.

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5. Disease states :-
1. Gastric diseases (Achlorhydric patients) :-
 They may not have adequate production of acids in the stomach; stomach
HCl is essential for solubilizing insoluble free bases.
 Many weak bases drugs that cannot form soluble salts and remain
undissolved therefore unabsorbed. Salt form of these drugs cannot be
prepared because the free base readily precipitates out.
 Eg. :- Dapsone, itraconazole, ketoconazole.
2. Cardiovascular diseases :-
 Several changes associated with congestive cardiac failure influence
bioavailability of a drug viz. oedema of the intestine, decreases blood flow
to the GIT and gastric emptying rate and altered GI pH, secretions and
microbial flora.
3. Hepatic diseases :-
 Disorders such as hepatic cirrhosis influence bioavailability mainly of
drugs that undergo considerable first pass hepatic metabolism. Eg. :-
Propanolol.

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6. Blood flow through the GIT :-

 It plays a major role in absorption by continuously maintaining the
concentration gradient across the epithelial membrane.
 The GIT is extensively supplied by blood capillary network.
 Blood flow is important for actively absorption of drugs.
 Absorption of polar molecules doesn’t depends on the blood flow
but lipid soluble molecule highly depends on the blood flow.
 Food influences blood flow to the GIT. Perfusion increases after
meals and persist for few hours but absorption is not affected.
7. Gastrointestinal contents :-
1. Food drug interactions :-
 Presence of food may either delay, reduce, increase or may not
affect drug absorption.
 Digested foods contain amino acids, fatty acids and many
nutrients that may affect intestinal pH and solubility of drugs.

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2. Fluid volume :-
 Large fluid volume results in better dissolution, rapid gastric emptying
and enhanced absorption.
 Eg. :- Erythromycin is better absorbed when taken with a glass of water
under fasting condition than when taken with meals.
3. Interaction of drug with normal GI constituents :-
 The GIT contains a number of normal constituents such as mucin which
is a protective mucopolysaccharides that lines the GI mucosa, interact
with streptomycin.

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8. Presystemic metabolism :-
 The loss of drugs through biotransformation by such eliminating
organs during the passage to systemic circulation is called as first
pass or presystemic metabolism.
 Complete absence of the drug in plasma after oral administration
is indicative of the first pass effects.
 The four primary systems which affect the presystemic
metabolism of a drug :-
1. Luminal enzymes :-
 The primary enzyme found in gastric juice is pepsin. Lipases,
amylases and proteases are secreted from the pancreas into the
small intestine in response to ingestion of food.
 Pepsin and the proteases are responsible for the degradation of
protein and peptide drugs in the lumen.

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2. Gut wall enzymes :-

 These are also called as mucosal enzymes. They are present in
stomach, intestine and colon. Alcohol dehydrogenase (ADH) is
an enzyme of stomach mucosa that inactivates ethanol.
 Eg. :- Sulfation of ethinyl estradiol and isoprenaline.
3. Bacterial enzymes :-
 These are mainly localized within the colonic region of the gastro-
intestinal tract, also secrete enzymes which are capable of a
range of reactions.
 Eg. :- Sulphasalazine, is a prodrug of 5 – aminosalicylic acid
linked via an azo bond to sulphapyridine.
4. Hepatic enzymes :-
 Several drugs undergo first pass metabolism, the highly extracted
ones being isoprenaline, propranolol, diltiazem etc.

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References
1. Brahmankar DM, Jaiswal Sunil B., “Biopharmaceutics and
pharmacokinetics”, Edition :- 3rd, Year :- 2017, Published by
Vallabh Prakashan, Page No. :- 24 – 78.
2. Wikipedia.

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 Amity Institute of Pharmacy

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