10/25/2023

FACTORS AFFECTING DRUG

ABSORPTION
Muhammad Faheem
Lecturer, Department of Pharmacy
University of Swabi

A-Physicochemical
Factors

I- Patient Related
Factors Factors
Affecting
Drug
Absorptio
n II- Pharmaceutical
Factors B-Dosage form
Characteristics
and
Pharmaceutical
Ingredients

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I-Patient related Factors

This includes factors related to anatomical, physiological and
pathological characteristics of the patients.
 GIT and various transport Mechanisms
 GI motility and gastric emptying
 Intestinal motility and transit time
 Blood Perfusion of GIT
 Gastrointestinal pH
 Disease State
 Gastrointestinal Contents
 Contact Time
 Surface area

II-Pharmaceutical Factors
A-Physicochemical Factors
 Particle Size and effective Surface area
 Drug Solubility and Dissolution Rate
 Chemical Nature
 Salt Form
 Crystal Form
 Amorphous Form
 Solvate
 Complexation
 Drug Pka and pH of Dissolving Medium

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B-Dosage form Characteristics and

Pharmaceutical Ingredients
 Nature and type of Dosage Form
 Manufacturing Variables
 Pharmaceutical Ingredients/ excipients
 Product age and Storage Conditions

I. Patient Related Factors

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GIT & Various

Transport Mechanisms

Gastrointestinal (GI) Physiology:

 The gastrointestinal tract is a muscular tube approximately 6 m in length
with varying diameters.
 GIT comprises of number of compartments, there primary functions are:
 Secretion
 Digestion
 Absorption
 It stretches from the mouth to the anus and consists of four main
anatomical areas: the oesophagus, the stomach, the small intestine and
the large intestine or colon.
 These grossly differ from each other in terms of anatomy, function,
secretions, pH

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Oral Cavity
Main Secretion: Saliva

pH: 7 (approx.)

Saliva contains
Ptyalin (salivary amylase)-digests starches.
Mucin, a glycoprotein that lubricates food, may also
interact with drugs.

About 1500 mL of saliva secreted per day.

 The oral mucosa has a thin epithelium and rich

vascularity, which favor absorption; however, contact
is usually too brief for substantial absorption.

 A drug placed between the gums and cheek (buccal

administration) or under the tongue (sublingual
administration) if retained for longer time, will
enhancing absorption.

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Esophagus
Connects pharynx and the cardiac orifice of the
stomach.

pH of the fluids in the esophagus is 5–6.

Lower part - esophageal sphincter prevents acid

reflux from the stomach.

Very little drug dissolution occurs in this part.

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Stomach
 The stomach is a J -haped expanded bag, located just
left of the midline between the oesophagus and small
intestine.

 Fasting pH is 2-6.

 In presence of food 1.5-2.

 The stomach can hold up to 1.5-4 liters of material.

 The stomach has a relatively large epithelial surface, but

its thick mucous layer and short transit time limit
absorption.

 Most absorption occurs in the small intestine therefore

gastric emptying is often the rate-limiting step.

 Food, especially fatty food, slows gastric emptying (and

rate of drug absorption), explaining why taking some
drugs on an empty stomach speeds absorption.

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 Drugs that affect gastric emptying (e.g. parasympatholytic

drugs) affect the absorption rate of other drugs.

 Food may enhance the extent of absorption for poorly

soluble drugs (e.g. griseofulvin) and reduces for drugs that
are degraded in stomach (e.g. penicillin G).

 Gastrin released from G cells, many enzymes and intrinsic

factor for Vit B 12 are also secreted into lumen of stomach.

Pepsin responsible for initiating protein digestion is also

secreted into stomach.

Stomach: Continue…….

 Acidic pH……acidic drugs unionized……..

 Absence of villi & microvilli.

 Not principal region for drug absorption because:

 The total mucosal region is small
 More secreting cells than absorptive cells
 Gastric residence time is limited

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Small Intestine
The small intestine is the site where most of the chemical and
mechanical digestion is carried out.

villi line the small intestine which absorbs digested food into the
capillaries.

Most of the food absorption takes place in the jejunum and the ileum.

The functions of a small intestine is the digestion of proteins into

peptides and amino acids principally occurs in the stomach but some also
occurs in the small intestine.

lipids (fats) are degraded into fatty acids and glycerol; and
carbohydrates are degraded into simple sugars.

Characteristics:
 Large surface area:
 Due to folds in intestinal mucosa kerckrings result in 3 fold
increase of surface area.
 Surface of folds possesses finger like projections called as villi
(Increases surface area 30times).
 The surface of villi protrudes several microvilli (Increases surface
area 600 times)

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 Great length of small intestine:

It is more than 200 square meters

 Greater Blood Flow:

The blood flow to small intestine is 6 to 10 times that of stomach.

 Favorable pH range:
pH range is 5 to 7.5 favorable for drugs to remain unionized.

 Slow Peristaltic Movement:

Prolongs the residence time of drug in intestine.

 High permeability:
The intestinal epithelium is dominated by absorptive cells.

The three main parts of the small intestine are:

1. The Duodenum
2. The Jejunum
3. The Ileum

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1. The Duodenum
 The duodenum is a hollow jointed tube connecting the
stomach to the jejunum. It is the first and shortest part of the
small intestine.

 The bile and pancreatic juices enter the duodenum. Trypsin,

chymotrypsina and carboxypeptidase hydrolyze the protein
into amino acids.

 pH 6-6.5 and is optimum for enzymatic digestion of protein

and lipids.

 The presence of carbonate neutralize the acid chime

entering from stomach.

 Many ester-pro-drugs are hydolysed during absorption.

 Presence of proteolytic enzymes causes the break down

of protenious drugs.

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2. The Jejunum
 The Jejunum is located between the distal end of
duodenum and the proximal part of ileum.

 The inner surface of the jejunum is the mucous

membrane covered with projections called villi, that
increases the surface area of tissue available to
absorb nutrients from the gut contents.

 Digestion of the protein and carbohydrates

continue in the presence of bile and pancreatic
secretions.

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Structure of Villus

Villi cover the surface of the intestinal mucosa. Each

villus consists of a layer of columnar epithelial cells
and a central core of connective tissue.

Microvilli project from the epithelial cells, forming

an absorptive brush border. Embedded in the
connective tissue core are the lymphatic lacteals and
blood capillaries.

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 Fatty acids diffuse across the membranes of the

microvilli and into the epithelial cells. Short-chain fatty
acids are transported directly to the blood capillaries
embedded in the core of the villus.

 Long-chain fatty acids are packaged into

chylomicrons and transported to the lymphatic lacteals.

3. The Ileum
 The wall itself is made up of folds, each of which
has many villi, on its surface. In turn, the epithelial
cells which line these villi possess even larger
numbers of micro villi.

 The cells that line the ileum contain the protease

and carbohydrate enzymes responsible for the final
stages of protein and carbohydrate digestion. These
enzymes are present in the cytoplasm of the
epithelial cells.

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 The villi take the amino acids and glucose produced

by digestion to the hepatic portal vein and the liver.

 The terminal ileum continues to absorb bile salts, and

is also crucial in the absorption of fat-soluble vitamins
(Vitamin A, D, E and K). For fat-soluble vitamin
absorption, bile acids must be present. It also absorb
vitamin B12 and bile salts.

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Large Intestine
 The large intestine extends from the end of the ileum
to the anus. It is about 5 feet long, being one-fifth of
the whole extent of the intestinal canal.

 The large intestine is divided into the cecum, colon,

rectum, and anal canal. In its course, describes an arch
which surrounds the convolutions of the small
intestine. It commences in the right iliac region, in a
dilated part, the cecum.

 There are trillions of bacteria, yeasts, and parasites living

in our intestines, mostly in the colon. Over 400 species of
organisms live in the colon.

 Most of these are very helpful to our health, while some

of these are harmful. Helpful organisms synthesize
vitamins, like B12, biotin, and vitamin K. These
organisms also breakdown toxins and stop proliferation
of harmful organisms.

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 Some organisms stimulate the immune system and

produce short chain fatty acids (SCFAs) that are
required for the health of colon cells and help prevent
colon cancer.

 There are many beneficial bacteria but some of the most

common and important are Lactobacillus Acidophilus
and various species of Bifidobacterium. These are
available as "probiotics" from many sources.

 Colon is lack of Villi thus having limited drug

absorption. Few drugs like theophylline and metoprolol
absorb from this region.

 The drug absorption from rectum depends upon the

placement of suppository that are absorbed by lower
hemorrhoidal vein.

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GI Motility and
Gastric Emptying
Time

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Gastrointestinal Motility
 GI motility tends to move the drug through the alimentary canal,
so the drug may not stay at the absorption site.

 For drugs given orally, an anatomic absorption window may exist

within the GI tract in which the drug is efficiently absorbed.

 Drugs contained in a non biodegradable controlled-release dosage

form must be completely released into this absorption window to
be absorbed before the movement of the dosage form into the large
bowel.

 The transit time of the drug in the GI tract depends on the

physiochemical and pharmacologic properties of the drug, the type
of dosage form, and various physiologic factors.

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Gastric Emptying
Apart from dissolution of a drug & its permeation through the bio membrane, the
passage from stomach to the small intestine, called as gastric emptying.

This is accomplished by three mechanisms: (1) Peristaltic waves, (2) systolic

contractions of the antrum, and (3) reduction in size of the stomach.

Rate limiting step, because the major site of drug absorption is intestine.

It increases bioavailability of a drug.

It is first order process.

Generally drugs are better absorbed in the small intestine (because of the
larger surface area) than in the stomach, therefore quicker stomach emptying
will increase drug absorption.

 For example, a good correlation has been found between stomach

emptying time and peak plasma concentration for acetaminophen. The
quicker the stomach emptying (shorter stomach emptying time) the higher the
plasma concentration.

 Also slower stomach emptying can cause increased degradation of drugs in

the stomach's lower pH; e.g. L-dopa.

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Dependence of peak acetaminophen plasma concentration as a function of stomach

emptying half-life

Rapid gastric emptying advisable where,

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Delayed gastric emptying advisable where,

Factors Affecting Gastric Emptying

Volume of meal:
The larger the starting volume, the greater the initial rate of emptying, after
this initial period, the larger the original volume, the slower the rate of
emptying.

Composition of meal
The rate of gastric emptying for various food materials is in the following order:
carbohydrates>proteins>fats.

Physical state:
Liquid meal takes less time as compared to solid meals.

Temperature of the meal:

High or low temperature of the ingested fluid (in comparison to body
temperature) reduces the gastric emptying rate.

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Body Posture:
Gastric emptying is favored while standing and by lying on the right side since
normal curvature of the stomach provides a downhill path. Whereas lying on the
left side or in supine position retards it.

Exercise:
Vigorous physical training retards gastric empting.
(over-activation of the sympathetic nervous system)

Emotional state:
Stress and anxiety delay gastric emptying.

Drugs:
Drugs that retards gastric emptying: Antacids, Anticholinergics, Narcotic analgesics and tri
cyclic anti depressants etc.
Drugs that stimulates gastric emptying: Metaclopramide, Domperidone, Cisapride etc.

Electrolyte and Osmotic Pressure :

Water, isotonic solutions and solutions of low salt
concentration empty stomach rapidly. Whereas higher
electrolyte concentration decreases gastric emptying rate.

Viscosity:
Rate of emptying is greater for less viscous solutions.

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Intestinal Motility
and Transit Time

Intestinal Motility
 Intestinal motility is a continuation of the gastric motility,
and display motility patterns similar to gastric motility.

 The main difference is that the whole stomach is always in

the same phase, whereas different segments of the intestine
may be in different phases.

 Gastric contraction in the fasted state also tends to be

stronger than that of the small intestine.

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Fasted Pattern
Each motility cycle takes approximately 140-150 min to complete,
which is similar to gastric motility under fasted condition.
1. Phase I - Basal activity
2. Phase II- Random activity
3. Phase III - Intense contraction that moves large
unabsorbable substance to large intestine. One
contraction starts at the duodenum, whereas the other
starts at ileocolonic junction.
4. Phase IV - Transition between phase III and I.

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Fed Pattern

1. Contraction serves to mix food and promote

contact between food ingredients and the
absorption surface.
2. An increase in the solid food content of a meal
tends to increase the number of contractions.
3. An increase in the carbohydrates also may
increase the number of contractions

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Blood Perfusion
of GIT

 The GIT is extensively supplied by blood capillary network and blood

flow rate to GIT (splanchnic circulation) is 28% of the cardiac output.
 Therefore, it helps in maintaining sink conditions and concentration
gradient for drug absorption by rapidly removing drug from the site of
absorption

S. No Drugs Blood Flow

Effect
1 highly lipid soluble drugs More
2 Some polar lipophilic drugs like Intermediate
ethanol, glycerol, etc
3 Polar compounds Less

Table : Influence of blood flow effect on various types of drugs

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Gastrointestinal PH

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GI fluid pH affects in several ways:

Disintegration:
The Disintegration of some drugs is pH sensitive with
enteric coating the coat dissolves in only the intestine at
specific PH.

Dissolution :
A large no of drugs whose solubility is greatly affected by
pH are either weak acids or weak bases.

 Weakly acidic drugs dissolves rapidly in alkaline pH

of the intestine whereas basic drugs dissolve in the acidic
pH of the stomach.

Stability :
 GI pH also affect the chemical stability of drugs .
e.g., the acidic stomach pH gives a degradation of
penicillin G and erythromycin. So such drugs to be
formulated by preparing prodrugs Ex. Erythromycin
estolate or in any other way .
Absorption:
 Depending upon the pKa and weither it is an acidic
or basic drug the amount of drug that would exist in the
unionized form at site of absorption.

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Disease State

 Several disease state may influence the rate and

extent of drug absorption.
 Following major classes of disease may influence
bioavailability of drug.
GI diseases
CVS disease
Hepatic disease
Lungs Diseases
Other Diseases

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GI diseases

Diarrhea
Decreases absorption because of decreased contact time.

Malabsorptive Syndrome
Decreases absorption

Achlorhydria

 Achlorhydricpatients may not have adequate production of acids in the

stomach; stomach HCl is essential for solubilizing insoluble free bases.

Many weak-base drugs that cannot form soluble salts will remain

undissolved in the stomach when there is no hydrochloric acid present and

are therefore unabsorbed. Salt forms of these drugs cannot be prepared

because the free base readily precipitates out due to the weak basicity.

 Dapsone, itraconazole, and ketoconazole may also be less well absorbed in

the presence of achlorhydria.

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Celiac disease:
 (characterized by destruction of villi and microvilli) abnormalities
associated with this disease are increase GI emptying rate and GI
permeability, alter intestinal drug metabolism.
Crohn’s disease:
 Crohn's disease is an inflammatory disease of the distal small intestine
and colon. The disease is accompanied by regions of thickening of the
bowel wall, overgrowth of anaerobic bacteria, and sometimes obstruction
and deterioration of the bowel. The effect on drug absorption is
unpredictable, although impaired absorption may potentially occur
because of reduced surface area and thicker gut wall for diffusion.

CVS Diseases
In CVS diseases blood flow to GIT decrease, causes decreased
drug absorption.

Hepatic Diseases
Disorders like hepatic cirrhosis influences bioavailability of
drugs which under goes first pass metabolism.

Lungs Diseases
e.g., Emphysema (air sacs of the lungs are damaged and
enlarged). Emphysema affects the absorption of volatile gases
through the pulmonary route.

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Other Diseases
Parkinsons disesase
 Parkinson's disease may have difficulty swallowing and greatly
diminished gastrointestinal motility. A case was reported in which the
patient could not be controlled with regular oral levodopa medication
because of poor absorption. Infusion of oral levodopa solution gave
adequate control of his symptom.

 HIV-AIDS patients are prone to a number of gastrointestinal (GI)

disturbances, such as increased gastric transit time, diarrhea, and
achlorhydria. Rapid gastric transit time and diarrhea can alter the
absorption of orally administered drugs. Achlorhydria may or may not
decrease absorption, depending on the acidity needed for absorption of a
specific drug. Indinavir, for example, requires a normal acidic environment
for absorption. The therapeutic window of indinavir is extremely narrow,
so optimal serum concentrations are critical for this drug to be efficacious.

Gastrointestinal
Contents

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@

Gastro intestinal contents:

1) food- drug interactions :

The presence of food will affect absorption in following way

a) delay absorption

b) decreased absorption :

c)increased absorption :

d) In some cases it do not affect

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Contact Time

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 The drug must have a sufficient residence time at the absorption

site for optimal absorption.

 In case of increased motility in GIT such as in diarrhea, the drug

have a very limited/brief contact time and less opportunity for
adequate absorption.

 The average normal small intestine transit time is 4-8 hrs (during
fasted state) and may take 8-12 hrs (during fed state).

Surface Area

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 “Greater the surface area of the absorbing membrane, maximum will

be absorption.”

 Small intestine……fold of kerckings …………………..

……………………vili………………….microvili………

 In addition…..perfusion of small intestine……..

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II. Pharmaceutical
Factors

A-Physicochemical
Factors

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Particle Size and

effective Surface area

 Particle size and surface area are inversely related with each other,
“Smaller the particle size, the greater the surface area, and the
high the dissolution rate.”

 Two types of surface area are defined:

Absolute surface area

Total area of the solid surface of any particle

Effective surface area

Area of the solid surface exposed to dissolution medium

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 “The greater the effective surface area, the more intimate contact
between the solid surface and aqueous solvent and the faster the
dissolution.”

 Thus P.S reduction results in increased bioavailability, provided that

the absorption of drug is dissolution rate dependent.

 Example
1. In Griseofulvin, where particle size reduction from 10 micrometer to
2.7 micrometer, results in increase in surface area of 0.4 m2 to 1.5 m2,
increasing the absorption twice.

PROBLEM WITH P.S REDUCTION

 In case of hydrophobic drugs, particle size reduction technique can

result in decrease in effective surface area and fall in dissolution
rate.

REASONS
Three basic reasons

a) Hydrophobic surface of the drug adsorb air onto their surface which
inhibit the wettability and such powder floats on the dissolution
medium.

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b) Particle aggregate to form larger particles due to their high surface

energy and hence either float or settle at the bottom of dissolution
medium.

c) Extreme particle size reduction may impart surface charges that may
prevent wetting and contact between drug and dissolution medium.

Examples of hydrophobic drugs are:

S.No Drug Name Solubility in water

1 Phenobarbitone 1 : 1000

2 Phenacetin 1 : 1300
3 Aspirin 1 : 300
4 Digoxin Insoluble
5 Nitrofurontoin Insoluble
6 Sulphadiazine Insoluble
7 Naproxen Insoluble
8 Ibuprofen Insoluble

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Solution of the Problem

 Use of surfactant as wetting agent, that decreases interfacial
tension and displaces the adsorbed air with solvent.
 For example, Tween 80 increases bioavailability of Phenacetin by
promoting its wettability.

 Adding hydrophilic diluent such as PEG, PVP, dextrose etc ,which

render hydrophobic particles hydrophilic.

NOTE :
Particle size reduction and subsequent increase in effective
surface area in not always advisable especially when drugs are
unstable and degraded in solution form.
For example, Penicillin G and erythromycin
Particle size will increase the effective surface area, will
result in their chemical degradation in gastric fluid, and
reduction in absorption of intact drug.

To minimize their degradation, such drugs should be

in solid unit state.

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Drug Solubility and

Dissolution Rate

SOLUBILITY
“The amount of solute dissolved per unit volume of solvent at
specific temperature and pressure to give a saturated solution is
called solubility.”

Intrinsic solubility
Solubility of drugs in unionized form is called intrinsic
solubility.

DISSOLUTION
“The process in which a solid substance solubalize in a given
solvent i.e., mass transfer from solid surface to liquid phase is
called dissolution.”

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DRUG DISSOLUTION
PROCESS

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 The effectiveness of a tablet in releasing the drug for

absorption depends on four steps -

1. The initial step involves the breaking of a tablet into

granules (disintegration).

2. Some times, these granules further break to yield fine

particles (deaggregation)

3. The next step involves the releasing of the drug into solution
(dissolution)

4. Absorption.

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Solubility terms given by USP-38

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BIOPHARMACEUTICS CLASSIFICATION SYSTEM (BCS)

BCS Class Solubility Permeability Absorption Rate limiting Step Examples

NSAIDS,
I High High Well Gastric Emptying Metoprolol,
Paracetamol

Carbamazepine,
II Low High Variable Dissolution Digoxin,
Spironolactone

Captopril,
III High Low Variable Permeability Insulin,
Frusemide
Neomycin,
IV Low Low Poor Case by case
Taxol

THEORIES OF DISSOLUTION
 Three Theories:

1. Diffusion layer model / Film theory

2. Danckwert’s model / Penetration or Surface renewal theory

3. Interfacial barrier model / Double barrier or

Limited solvation theory

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1) Diffusion layer model

 It involves two steps :

1. Solution of the solid to form stagnant film or diffusive layer which is
saturated with the drug.
2. Diffusion of the soluble solute from the stagnant layer to the bulk of
the solution; this is rate determining step in drug dissolution.

 The rate of dissolution is given by Noyes and Whitney:

dC/dt = k (Cs- Cb)…………(1)

where,
dC/dt = dissolution rate of the drug
k = dissolution rate constant
Cs= concentration of drug in stagnant layer
Cb= concentration of drug in the bulk of the solution at time t

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Nernst and Brunner incorporated Fick’s first law of diffusion and modified
the Noyes-Whitney’s equation to :

dC/dt = DAKw/o (Cs-Cb) ………….(2)

Vh
where,
D = diffusion coefficient of drug
A = surface area of dissolving solid
Kw/o = water/oil partition coefficient ofdrug
V = volume of dissolution medium
h = thickness of stagnant layer
(Cs – Cb) = conc. gradient for diffusion of drug

Limitation :
The Noyes-Whitney’s equation assumes that the surface area of the dissolving solid
remains constant during dissolution, which is practically not possible for dissolving
particles.
Hence, dissolution methods that involves use of constant surface area discs are
employed to determine the rate of dissolution.
To account for the particle size decreases and change in the surface area
accompanying dissolution, Hixson and Crowell’s cubic root law of dissolution is used:

Wo1/3– W 1/3= K.t …………(3)

where,
W = mass of drug remaining to be dissolved at time t
K = dissolution rate constant
Wo = original mass of the drug

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2) Danckwert’s model
1. Danckwert takes into account the eddies or packets that are present in the agitated
fluid which reach the solid-liquid interface, absorb the solute by diffusion and carry
it into the bulk of solution.
2. These packets get continuously replaced by new ones and expose to new solid surface
each time, thus the theory is called as surface renewal theory.

 The Danckwert’s model is expressed by equation:

V. dC/dt= dm/dt = A ( Cs-Cb). √(γ.D)……….(4)

where,
m = mass of solid dissolved
γ = rate of surface renewal

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3) Interfacial barrier model

 The diffusion layer model and Danckwert’s model were

based on two assumptions:
1. The rate determining step that controls dissolution is the mass
transport.
2. Solid-solution equilibrium is achieved at the solid/liquid interface.
 According to the interfacial barrier model, an intermediate
concentration can exist at the interface as a result of solvation
mechanism and is a function of solubility rather than diffusion.
When considering thedissolution of a crystal, each face of crystal
will have a different interfacial barrier.

 Such a concept is given by the following equation :

G = Ki (Cs-Cb)………(5)
where,
G = dissolution rate per unit area
Ki = effective interfacial transport constant

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Chemical Nature
Salt Form
Crystal Form
Amorphous Form
Solvate
Complexation
Drug Pka and pH of Dissolving Medium

Salt Form

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 Salts of weak acids and weak bases generally have much higher aqueous
solubility than the free acid or base.

 The dissolution rate of a weakly acidic drug in gastric fluid (pH 1 – 3.5)
will be relatively low.

 If the pH in the diffusion layer increased, the solubility, Cs, of the acidic
drug in this layer, and hence its dissolution rate in gastric fluids would be
increased.

The pH of the diffusion layer would be increased if the chemical

nature of the weakly acidic drug was changed from that of the
free acid to a basic salt (the sodium or potassium form of the free
acid.

The pH of the diffusion layer would be higher (5-6) than the low
bulk pH (1-3.5) of the gastric fluids because of the neutralizing
action of the strong (Na+, K+ ) ions present in the diffusion layer.

The drug particles will dissolve at a faster rate and diffuse out of
the diffusion layer into the bulk of the gastric fluid, where a
lower bulk pH.

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Thus the free acid form of the drug in solution, will precipitate
out , leaving a saturated solution of free acid in gastric fluid.

This precipitated free acid will be in the form of:

 very fine,
non-ionized,
wetted particles which have a very large surface area in contact with
gastric fluids, facilitating rapid redissolution when additional gastric
fluid is available.

 Barbiturates Na, Naproxen Na, Tolbutamide Na

Note: Tolbutamide Na in 0.1 M HCl solution has 500 times more

solubility than its free acidic form.

Dissolution process of a salt form of a weakly acidic

drug in gastric fluid.

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 One example is the dissolution and bioavailability profiles of Penicillin V with various
salts.

 Some salts have lower solubility and dissolution than in free form
For example Al and pamoate salts
 In these cases, insoluble film of Al(OH)3 and pamoic acid are formed
……………………………

 Na acetyl salicylic acid (Na salt of aspirin) is much prone to

hydrolysis than in free acid.

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Crystal Form

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Amorphous Form

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Solvates

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Complexation

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 Complex formation may occur within or/and in the body fluids.

 Complexation may be beneficial or harmful for absorption.
HARMFUL COMPLEXATION

BENEFICIAL COMPLEXATION

Drug Pka and GI pH

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B-Dosage form Characteristics and Pharmaceutical Ingredients

 Nature and type of Dosage Form
 Manufacturing Variables
 Pharmaceutical Ingredients/ excipients
 Product age and Storage Conditions

Nature and Type of

Dosage form

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Manufacturing/Processing
Variables

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Pharmaceutical Ingredients
(Excipients)

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Product Age and Storage

Conditions

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ABSORPTION OF
DIFFERENT ORAL
DOSAGE FORMS

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