Bioavailability

The fraction of unchanged drug reaching the systemic

circulation in following administration by any route
Measure of both rate and extent of drug that reaches
the general circulation from an administered dosage
form.

Drug in dosage form

Desired Effect

A successful Therapy

Attain and maintain an adequate

drug concentration at active site

Excretion

Blood
conc.

MTC

Metabolism
Distribution
Absorption

Drug dissolved in GIT fluid

Ability of drug dosage form to release drug after

administered to patient

MEC
time

Drug in Dosage Form

Solid Dosage Form

Granules

Disintegration

Very limited
dissolution

Fine particles
Deaggregation

Limited
dissolution

Optimum
dissolution

Drug is dissolved in
GIT fluid
Membrane
Absorption

Drug in blood
Sequence of event involved in the dissolution and absorption of a drug
from tablet dosage form

Determination of the Bioavailability

Comparing plasma concentration
of drug after particular route of
administration with plasma drug
level by injection

Blood Conc.
Drug injected

AUC injected

Drug given orally

AUC Oral
Drug administered

Time (hours)

AUC oral
Bioavailability =

X 100 %
AUC Injected

Blood Conc.

Time (hours)
Two 250 mg. Erythromycin Tablet No Film or Enteric Coating
Two 250 mg. Erythromycin Tablet Film Coated
Two 250 mg. Erythromycin Tablet Enteric Coated

Factor affecting Bioavailability :

I.
II.
III.
IV.

Patient variable
Pharmaceutical variable
Route of administration
Time of administration

I. Patient variable
Anatomy and Physiology patient factors :
1. Anatomical factor :
Stomach :
* Primary function is not absorbing membrane
* Stomach content contact with epithelial cell
30 2 hr provides weakly acidic drug absorption
Small Intestine : Villi and microvilli optimum absorption
Large intestine : Absorption is not completely

2. Physiological factor :
a.
Membrane area of absorptive site :
* Stomach abs. of weakly acidic drug
* Intestine optimum absorption
b.
pH of GIT fluid :
* Various pH of GIT fluid
# pH fraction of un/dissociated drug
if the fraction of undiss. Absorption
* With meal pH , and will be slowly
c. Gastric emptying time :
* Optimal absorption is in small intestine
The rate of gastric emptying time influences
drug absorption
* Acid/enzyme-labile drugdegradation Intact drug

d.

Intestinal transit :
* Longer the period time in small intestine absorption
bioavailability
* Motility contact availability

e. Degradation and metabolism in GIT / Gut wall

metabolism
- Susceptible to Acid/enzymatic degradation bioavailability
ex.: Pro-drug ; Clindamycin palmitate degraded
become Clindamycin bioavailability
f. Hepatic metabolism ; First pass effect bioavailability

Transport mechanism of drug across GI membrane

Water

Water

Protein
Lipid
Membrane is phospholipid bilayer :
Protein lipid lipoidal layer permeable
to hydrophobic molecule
Pore 0,4 nm
molecule size < 0,4 nm pore
molecule size >>>> passive diffusion

GIT Fluid

GIT membrane

Blood

Drug in solution

Drug bring
into systemic
circulations

Partition

Diffusion

Partition

Drug absorption
Generally passive diffusion
Active transport ; Levodopa, Thiamin etc.
Ion paring ; Tetracycline

II. Pharmaceutical Variable

A. Physicochemical properties of drug
B. Manufacturing technique of drug
C. Drug dosage form

A.

Physicochemical properties of drug :

* Particle size :
Smaller greater surface area dissolution rate
* Solubility of drug :
Absorption
too hydrophilic
too lypophylic
* Solvate formation ; hydrated, unhydrate form
Ex.: Amoxcicillin unhydrate is easily dissolved in water
* Polymorphism ; amorphous, crystalline
Crystalline form is easily dissolved in water
* Complexation ;
- excipient in dosage form
- natural component in GIT
* Salt form
* Wettability

B. Manufacturing process :
1. The composition of the dosage form
For ex.:
other material in formulation (adjuvant)
- Lubricating agents;
* hydrophilic
* hydrophobic agents diss.rate
- Disintegrating agents diss.rate
2. Manufacturing technique
Compression force

C. Dosage form
1. Solution :
- Disperse system
- Absorption (rate and/or extend) fastest and complete
- OOA rapid

2. Suspension / Emulsion
* Aqueous solubility Require the dissolution of drug
* Absorption < solution
* OOA < solution

3. Powder
- Dissolution process
- Particle size, solubility etc
- Possibility absorption of drug onto inert material
- Absorption < solution

4. Capsule:
-

Capsule shell
Hard gelatin caps. dissolve readily than soft capsule
Require dissolution process
Particle size, solubility, absorpt. Onto inert material
Absorption < powder

5. Tablet :
- The rate of absorption < powder
disintegration, deaggregation and dissolution process

6. Coated tablet :
- Sugar coated more easily soluble than film coated
- Factor influencing rate of absorption = factor in tablet
- Enteric coated tablet disintegrates in intestine alkaline
media
- Sublingual tablet placed under the tongue and will readily
absorbed by mucose membrane

7. Suppositories :
- Vaginal Supp. : local effect
- Rectal supp. : - local
- systemic

The dissolution rate of drugs (that resists to

gastric acid ) is
decline according to following sequence :
Solution suspension powder capsule tablet
sugar coated film coated enteric coated
prolong action (sustained released tablet)

III. ROUTE OF ADMINISTRATION :

1. Oral : With or without first pass effect
With a first-pass effect:
1. Metabolism in GI fluid and membrane :
Various pH solution, enzymes, mucous etc.
2. Hepatic metabolism
3. Excreted into the bile

drug plasma level

Bioavailability

Without a first-pass effect :

drug plasma level drug absorbed

2. Rectal :
- first-pass effect partially avoided
- local effect
- absorption unpredictable

3. Parenteral
1. Intravenous :

- No absorption process
- Complete drug availability
- Bioavailability 100%

2. Intramuscular

- Drug from aqueous sol.absorbed > suspension

- OOA will vary
- Absorption into blood site of injection

4. Topical : Local effect

5. Inhalation :
- Very large surface for absorption
- Alveolar and vascular epithelial membrane are
quite permeable rapidly absorption
- Gaseous or volatile substances

RODA

Bioavailability (%)

Oral
Rectal
Parenteral
I.V.
I.M.
S.C.
Topical
Inhalation
Transdermal

5 to < 100
30 to < 100
100
75 to < 100
75 to < 100
5 to < 100
80 to < 100

Blood
concentration

II

III
IV
V
time

Theophyllin
I.
Intravenous 0.5 gr
II. Rectum (enema) 0.5 gr
III. Oral 0.5 gr
IV. Oral 0.3 gr
V. Rectal suppositoria 0.5 gr

IV. Time of administration :

Food can modify drug absorption through :
- Altering gastric emptying time
- Altering GIT secretion
- Competition on drug absorption
- Drug complexation
- GIT content viscosity

How to calculate Bioavailability of

drug :
Comparing :
Drug blood concentration or
urinary drug excretion

From

With

Any dosage form

Intravenously administration

Bioavailaability is expressed on scala 1 100 %

Parameter determining Bioavailability :

- Area Under Curve

( AUC )

- Height of Peak

( b max )

- Time of Peak

( t max )

AUC = The amount of drug absorbed following

administration at single dose of
drug
b.max
achieved

= Height of peak : the highest drug

after administration

t.max = Time of peak : the length of time

necessary to
achieved the highest drug
blood concentration
after administration