Call Girls in Delhi Triveni Complex Escort Service(🔝))/WhatsApp 97111⇛47426
Bioavailability
1. Bioavailability
Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D
Department of Pharmaceutics
Faculty of Pharmacy
Omer Al-Mukhtar University
Tobruk, Libya.
E-mail: nanjwadebk@gmail.com
2014/03/15 1
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
2. CONTENTS
1. Concept and terminology.
2. Methods of assessing bioavailability.
3. Evaluation and design of a single dose
bioequivalency study.
4. Determination of bioavailability and
bioequivalency in multiple dose regimen.
5. References.
2014/03/15 2
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
3. What is Bioavailability
• Bioavailability, Indicates measurement of the
rate and extent (amount) of therapeutically
active drug that reaches the systemic
circulation and is available at the site of
action.
2014/03/15 3
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
4. Concept of Bioavailability
• Rate and extent at which therapeutically active drug
reaches systemic circulation.
• The fraction of administered dose that reaches the
systemic circulation in contrast to that stated on
label.
• Rate & extent of absorption of unchanged drug from
its dosage form.
• A measure relative to some standard of rate &
amount of drug, which reaches the systemic
circulation unchanged following the administration
of dosage form.
2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar
University, Tobruk, Libya.
4
5. Why bioavailability studies
• FDA requires that the drug product is safe and
effective.
• Measure of bioavailability: AUC/dose.
• Absolute availability: Absolute availability for drugs
with approved NDA, bioavailability studies are
required for new drug formulations-bioequivalence to
the reference formulation.
• Relative availability: Relative availability for drugs
without full NDA, bioequivalence to the reference drug
in the standard formulation.
• For determining safety and efficacy of drug product.
2014/03/15 5
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
6. Types of Bioavailability
Absolute Bioavailability :-
If the systemic availability of a drug administered
orally is determined by doing its comparison with I.V.
administration, it is known as absolute
bioavailability.
2014/03/15 6
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
larextravascu
ravenousint
ravenousint
larextravascu
Dose
Dose
AUC
AUC
F ×=
7. Types of Bioavailability
Relative Bioavailability :-
If the systemic availability of a drug
administered orally is determined by doing its
comparison with that of an oral standard of
the same drug, it is known as a relative
bioavailability.
2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar
University, Tobruk, Libya.
7
1larextravascu
2larextravascu
2larextravascu
1larextravascu
rel
Dose
Dose
AUC
AUC
F ×=
8. Types of Bioavailability
Range of Bioavailability – 0 to 1.
It is usually expressed as percentages (%).
An absolute bioavailability of 1 (or 100%) indicates
complete absorption.
Relative bioavailability of 1 (or 100%) implies that the
bioavailability of drug from both the dosage forms is
the same but does not indicate the completeness of
the systemic drug absorption.
2014/03/15 8
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
9. Bioavailability of drug from dosage form
depends upon following.
Route of administration
Patient related factors
Physicochemical properties of the drug
Characteristics of the dosage form
2014/03/15 9
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
Types of Bioavailability
10. Bioavailability
• The influence of route of administration on
drug’s bioavailability is generally in the
following order
Parenteral > Oral > Rectal > Topical
• Most drugs are administered orally, for reason
of stability and convenience.
• The dose available to patient – Bioavailable
dose.
2014/03/15 10
Faculty of Pharmacy, Omer Al-Mukhtar
University, Tobruk, Libya.
13. Pharmacokinetic methods
( indirect )
1. Blood analysis
• Plasma level time studies or The plasma
concentration – time curve or blood level curve.
• A direct relationship exists concentration of drug at
the site of action & concentration of drug in the
plasma.
• Serial blood samples are taken after drug
administration & analyzed for drug concentration.
• A typical blood level curve obtained after oral
administration of drug.
2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar
University, Tobruk, Libya.
13
14. Pharmacokinetic methods
( indirect )
2. Urinary excretion data
• The method of determination bioavailability
provided that the active ingredient is excreted
unchanged in the significant quantity of urine.
• The cumulative amount of active drug excreted in
urine is directly proportional to extent of systemic
drug absorption.
• The rate of drug excretion is directly proportional to
rate of systemic drug absorption.
2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
14
15. Pharmacodynamic methods
( direct )
1. Acute pharmacological response
• Bioavailability can be determined from the acute
pharmacologic effect – time curve as well as from
dose response graph.
2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
15
16. Pharmacodynamic methods
( direct )
2. Therapeutic response
• This method is based on the observing the clinical
response to a drug formulation given to a patients
suffering from disease for which it is intended to be
used.
Eg. Anti inflammatory drugs, the reduction in the
inflammation is determined.
2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
16
18. Parameters determined
Pharmacokinetic parameters
• Peak Plasma Concentration (Cmax)
• Time of Peak concentration (tmax).
• Area Under Curve (AUC)
Pharmacodynamics parameters
• Minimum Effective Concentration (MEC) / Minimum
Inhibitory Concentration (MIC).
• Maximum Safe Concentration (MSC) / Maximum Safe Dose
(MSD).
• Duration of action
• Onset of action.
• Intensity of action.2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
18
19. AUC or Extent of absorption
can be measured by 3 methods
1.Planimeter
Instrument for mechanically measuring the area
2. Cut & weigh method
AUC is cut & weighed on analytical balance. The
weight obtained is converted to proper unit by
dividing it by the wt of a unit area of same paper.
3. Trapezoidal method
2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
19
20. AUC or Extent of absorption
can be measured by 3 methods
3. Trapezoidal method
AUC = ½ ( C1 + C2) (t2 – t1) + ½ (C2 + C3) (t3 – t2) +…….
½ (C n-1 + C n ) (tn – tn-1 )
C = Concentration
t = time
subscript= sample number
AUC = Area Under Curve
2014/03/15
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
20
21. • AUC-Area under curve
• Cmax- Maximum concentration
• Tmax -Time to maximum concentration
2014/03/15 21
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
Methods of assessing
bioavailability
22. Bioequivalence
- Bioequivalence means pharmaceutical equivalents or
pharmaceutical alternatives whose rate and extent
of absorption do not show a significant difference
when administered at the same molar dose of the
therapeutic moiety under similar experimental
conditions.
- Bioequivalence studies are usually performed to
compare the rate and/or extent of absorption of a
new drug product or a generic equivalent with that
of a recognized standard.
2014/03/15 22
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
23. Dosage forms that are to be evaluated only
for bioequivalence purpose.
Dosage forms meant for a single dose
administration for a therapeutic benefit such
as analgesic for relief of headache.
Evaluation and design of a single
dose bioequivalency study
2014/03/15 23
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
24. Evaluation and design of a single
dose bioequivalency study
2014/03/15 24
Faculty of Pharmacy, Omer Al-Mukhtar
University, Tobruk, Libya.
25. Determination of bioavailability and
bioequivalency in multiple dose regimen
Dosage forms designed to achieve special
release profiles. e.g. time-release products,
enteric-coated preparations.
Drugs undergoing first pass metabolism.
Special dosage regimens such as loading dose.
2014/03/15 25
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
26. Dosage forms designed to achieve special
release profiles. e.g. time-release products,
enteric-coated preparations.
Drugs undergoing first pass metabolism.
Special dosage regimens such as loading dose.
Determination of bioavailability and
bioequivalency in multiple dose regimen
2014/03/15 26
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
27. Bioavailability and Bioequivalence
Two dosage forms are Two dosage forms are
bioequivalent: not bioequivalent:
2014/03/15 27
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.
28. References
• “Biopharmaceutics & Pharmacokinetics”, D. M.
Brahmankar & Sunil B. Jaiswal, Vallabh Prakashan.
• “Text book of Biopharmaceutics & pharmacokinetics”,
Dr. Shobharani R. Hiramath.
• “Applied Biopharmaceutics & pharmacokinetics”,
Leon Shargel & Andrew B.C.
• www.google.com
2014/03/15 28
Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.