This document summarizes a seminar presentation on methods for determining bioavailability. It defines bioavailability as the rate and extent to which the active substance of a drug is absorbed and available at the site of action. It then describes the main objectives of bioavailability studies which include aiding new drug and formulation development. The key methods discussed for assessing bioavailability include measuring plasma drug concentration, urinary drug excretion, acute pharmacodynamic effects, clinical observations, and in vitro drug dissolution studies. Specific parameters are defined for each method such as Cmax, AUC, tmax, Du, and Emax. Finally, the document summarizes two literature articles that developed formulations to enhance the oral bioavailability of curcumin and edarav
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Methods For Determining Bioavailability
1. M.Pharm 2nd Semester Seminar
Subject : Biopharmaceutics
Topic : Methods For Determination Of Bioavailability
By:
Anindya Jana
M.Pharm 1st Year (Pharmaceutics)
Regd. No. : 1661611006
Date – 18-01-2017
2. Bioavailability
The rate & extent to which the active substance is absorbed from a drug product & becomes
available at the site of action.
Objective Of Bioavailability Studies
• Primary stages of development of new drug of a suitable dosage form for a new drug
entity.
• Determination of influence of excipients, patient-related factors and possible interaction
with other drugs on the efficiency of absorption.
• Development of new formulations of the existing drugs.
• Comparison of availability of other drug substance from different dosage forms.
3. Methods For Assessing Bioavailability
1. Plasma Drug Concentration
• Time for the peak plasma (blood) concentration (tmax).
• Peak Plasma drug concentration (Cmax).
• Area under the plasma drug concentration-time curve (AUC).
2. Urinary Drug Excretion
• Cumulative amount of drug excreted in the urine (Du).
• Rate of drug excretion in the urine (dDu/dt).
• Time for maximum urinary excretion (t).
3. Acute Pharmacodynamic Effect
• Maximum Pharmacodynamic Effect (Emax)
• Time for maximum pharmacodynamic effect.
• Area under the pharmacodynamic effect-time curve.
• Onset time for pharmacodynamic effect.
4. Clinical Observations
• Well controlled clinical trial.
5. In-Vitro Studies
• Drug Dissolution
4. Plasma Drug Concentration
• Measurement of drug concentration in blood, plasma or serum after drug administration.
• Indirect method.
• By appropriate blood sampling, an accurate description of the plasma drug concentration-time profile of the
therapeutically active drug substances can be obtained.
5. I. Time For The Peak Plasma (Blood) Concentration (tmax) : It is the time required to
reach maximum drug concentration after drug administration. The tmax can be used
as an approximate indication of drug excretion rate.
II. Peak Plasma Drug Concentration (Cmax) : Represent the maximum plasma drug
concentration obtained after oral administration of drug. Cmax provides indications
that the drug systemically absorbed to provide a therapeutic response.
III. Area Under The Plasma Drug Concentration-Time Curve (AUC) : Is a measurement of
extent of drug bioavaibility. The AUC reflects the total amount of active drug that
reaches the systemic circulation.
6. Urinary Drug Excretion Data
• The drug must be excreted in significant
quantities as unchanged drug in the urine.
• Indirect method.
I. Cumulative Amount of Drug Excreted In The
Urine (Du) : It is related directly to the total
amount of drug absorbed.
II. Rate of Drug Excretion In The Urine (dDu/dt) :
Rate of drug excretion is dependant on first
order elimination rate constant k and the
concentration of drug in the plasma Cp.
III. Time For Maximum Urinary Excretion (t) : It is
analogous to the tmax of plasma level data. Its
value decreases as the absorption rate
increases.
7. Acute Pharmacodynamic Effect
• This method is used when the quantitative
measurement of drug in plasma or urine
lacks an assay with sufficient accuracy and
reproducibility.
• For locally acting, non systemically absorbed
drug products, such as topical corticosteroids,
plasma drug concentrations may not reflect
the bioavaibility of the drug at the site of
action.
• The use of acute pharmacodynamic effect to
determine bioavailability requires
demonstration of dose response curve.
• Bioavailability is determined by
characterization of dose response curve.
8. Clinical Observation
• Well controlled clinical trials in humans
establish the safety and effectiveness
of drug products and may be used to
determine the bioavailability.
• Clinical approach is the least accurate,
least sensitive, and least reproducible.
• This approach may be considered
acceptable only when analytical
methods can not be developed to
permit use of one or other
approaches.
9. In-Vitro Studies
• The best way of assessing therapeutic
efficacy of drug with a slow dissolution rate
is in vivo determination of bioavaibility
which is usually done whenever a new
formulation is to be introduced into the
market.
• Drug dissolution studies may under certain
conditions give an indication to drug
bioavaibility.
• The in vitro drug dissolution rate should
correlate with in-vivo drug bioavaibility.
• Dissolution test often performed on several
test formulations of the same drug.
10. Literature Articles
1. Lei Li et. al. has developed Curcumin (CUR) nanosuspension to enhance CUR oral bioavailability using a
cost effective method different from conventional techniques.
• Curcumin (CUR), a Biopharmaceutics Classification System (BCS) class IV substance, is a promising drug
candidate in view of its good bioactivity.
• Nanosuspension is one of the most promising strategies to improve the oral bioavailability of insoluble
drugs.
11. Result
In vitro dissolution degree of the prepared CUR
nanosuspensions using TPGS or Brij78 as
stabilizer was greatly increased.
Pharmacokinetic studies demonstrated that the
oral bioavailability of CUR was increased 3.18
and 3.7 times after administration of CUR/TPGS
nanosuspensions or CUR/Brij78
nanosuspensions, when compared with the
administration of CUR suspension.
12. 2. Sanjay Garg et. al. has developed a Novel Oral Delivery System (NODS) of Edaravone (EDR) to enhance oral
bioavailability.
• Edaravone (EDR), a strong free radical scavenger, is known for its promising therapeutic potential in oxidative stress
(OS) associated diseases.
• Poor oral bioavailability is the major obstacle in its potential use.
• Oral liquid dosage form is the most preferred delivery method in paediatric, geriatric and specialised therapies.
Result
Drug release from NODS was slow, sustained and
significantly better as compared to suspension.
The significant reduction in metabolism and
improvement in permeability across the small
intestine were observed with NODS compared to free
EDR. The oral pharmacokinetic study showed 571%
relative bioavailability with NODS compared to EDR
suspension.
From the results obtained, NODS is a promising
candidate for use in OS associated diseases.
13. References
1. Shargel L, Pong S, Yu A; Bioavaibility & Bioequivalence; Applied Biopharmaceutics & Pharmacokinetics; Published
By Mc Graw Hill; 2005; P 460-464
2. Brahmankar M. D, Jaiswal B. S; Bioavaibility & Bioequivalence; Biopharmaceutics & Pharmacokinetics A Treasure;
Published By Vallabh Prakashan; 2010; P 319-326
3. Yutong Wang, Changyuan Wang, Jing Zhao, Yanfang Ding, Lei Li; A cost-effective method to prepare curcumin
nanosuspensions with enhanced oral bioavailability; Journal of Colloid and Interface Science; Vol 485; 2017; P 91-98
4. Ankit Parikh, Krishna Kathawala, Chun Chuan Tan, Sanjay Garg, Xin-Fu Zhou; Development of a novel oral delivery
system of edaravone for enhancing bioavailability; International Journal of Pharmaceutics; Vol 515; 2016; P 490-499