Pranesh biopharmaceutics.pdf NCP --Erode

Bioavailability
Prepared By: R.Pranesh,
B.Pharm 6th
Sem

Definition:
• The term bioavailability is defined as the rate and extent (amount) of absorption
of unchanged drug from its dosage form.
• The bioavailability of a drug from its dosage form depends upon 3 major factors.
• 1. Pharmaceutical factors related to physicochemical properties of the drug and
characteristics of the dosage form.
• 2. Patient-related factors.
• 3. Route of administration.

• The influence of route of administration on drug's bioavailability is generally in the following order
with few exceptions.
• Parenteral > Oral > Rectal > Topical.
• Within the parenteral route, intravenous injection of a drug results in 100% bioavailability.
• The dose available to the patient, called as the bioavailable dose, is often less than the
administered dose.
• The amount of drug that reaches the systemic circulation (i.e. extent of absorption) is called as
systemic availability or simply availability.
• The term bioavailable fraction F, refers to the fraction of administered dose that enters the
systemic circulation.
• F= Bioavailable dose /Administered dose

Objectives of Bioavailability:
• 1.Primary stages of development of dosage form of new drug entity to find its
therapeutic utility.
• 2.Determination of influence of excipients on absorption.
• 3.Development of new formulations of existing drugs.
• 4.Control of quality of drug products and influence of processing factors, storage
and stability on absorption.

Types of Bioavailabilty:
•There are two types of bioavailability
1. Absolute bioavailability.
2. Relative or comparative bioavailability.

Absolute Bioavailability
Definition :
• When the systemic availability of a drug administered orally is determined in comparison
to its intravenous administration, it is called as absolute bioavailability.
• It is denoted by symbol F.
• Intravenous dose is selected as a standard because the drug is administered directly into
the systemic circulation (100% bioavailability) and avoids absorption step.
• Intramuscular dose can also be taken as a standard if the drug is poorly water-soluble.

Drawbacks of absolute bioavailability :
There several drawbacks of using oral solution as a standard instead of dose.
1.Limits the pharmacokinetic treatment to one-compartment only; one cannot apply the most applicable
two-compartment kinetics to the data and all pharmacokinetic parameters cannot be determined
2. Differentiation between the fraction of dose unabsorbed and ) metabolised is difficult.
3. If the rate of oral absorption is not sufficiently greater than rate of elimination, the true elimination rate
constant cannot computed.

Measurement of bioavailability:
The measurement of bioavailability can be broadly divided into two
categories.
1.Pharmacodynamic methods.
2. Pharmacokinetics methods.

1. Pharmacodynamic methods:
•It is a direct measurement of drug effect on physiological process as a
function of time.
•In pharmacodynamic Methods, there are two major
pharmacodynamic Methods.
•They are
1.Acute pharmacological response.
2.Threupeutic response.

1 .Acute pharmacological response method
• It is used when Pharmacokinetics methods are difficult and inaccurate .
• Changes like ECG ,EEG pupil diameter related to time course is noted.
• Bioavailability is measured by construction of pharmacological effect time curve
and dose response curve.
• Measure for at least 3 biological half Lives.
Disadvantages:
• 1.Pharmacological response is more variable.
• 2. The observed response may be due to an active metabolite whose

2. Therapeutic response method
• It involves observing the clinical response of drug after administering to the
patients suffering from disease.
Disadvantages
• 1. Quantitation of observed response is too improper to allow for reasonable
assessment of relative bioavailability between two dosage forms of the same
drug.
• 2.Unless multiple-dose protocols are employed, a patient who required the drug
for a disease would be able to receive only single dose of the drug every few days
or perhaps each week.
• 3. Many patients receive more than one drug, and the results obtained from a
bioavailability study could be compromised because of a drug-drug interaction.

2.Pharmacokinetic Methods
• These are very widely used and based on the assumption that the
pharmacokinetic profile reflects the therapeutic effectiveness of a
drug. Thus, these are indirect methods.
•The two major pharmacokinetic methods are:
•1. Plasma level-time studies.
•2. Urinary excretion studies.

• Plasma level time studies.
• It is most reliable method and method of choice in comparison of urine data.
• Assumption of two dosage form having superimposable plasma level to
administration.
• With single dose administration it requires sampling for atleast 2 - 3 half Life.
• A graph is plotted for concentration in plasma vs collection time to Obtain plasma
level time profile

*For IV sampling must be started within 5 minutes and subsequently 15
minutes for at least 3 times.
*The drug follows one compartment 2 to 3 points and if two
compartment 5 to 6 points.
Key pharmacokinetic parameters ..
a) C max - it is minimum plasma drug concentration.
• It indicates rate of absorption Higher Cmax - faster absorption
b) Tmax - time to reach C max*Indicates how quickly drug absorbed
C) AUC - area under curve *Measures the extent of absorption

AUC-area under the curve
D-Dose administered

For Multiple dose study :
For steady state:

Method involves :
• Collecting samples at a time span equal to 7 biological at half Life.
• Analyzing unchanged drug in sample.
• Determining the amount excreted at each interval and cumulative
amount excreted.
2. urinary excretion studies principle:
Urinary excretion of unchanged drug is directly proportional to the plasma
concentration of drug.
E.g.: extensively excreted in urine as unchanged form - thiazide, diuretics
, sulphonamides.

Criteria to follow :
1.complete emptying of bladder to avoid errors from residue
addition.
2.Frequent sampling of urine to complete absorption clearly.
3.Fraction excreted unchanged in urine must remain constant.
KEY PARAMETERS :
dxu/dt:- It is the maximum urinary excretion rate.
Tu max:- Time of maximum urinary excretion rate.
Χυ ♾ -Total amount of Drug Excreted in Urine

Reference Books:
1.Brahmankar. Sunil.B.Jaiswal Page no: 255-263
2.Biopharmaceutics and pharmacokinetics,
-By Leon Shargel,Madhan

Pranesh biopharmaceutics.pdf NCP --Erode

More Related Content

Similar to Pranesh biopharmaceutics.pdf NCP --Erode

Recently uploaded

Pranesh biopharmaceutics.pdf NCP --Erode