Methods For Assesment Of Bioavailability

Bioavailability means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
Bioavailability studies are important in the Primary stages of development of a suitable dosage form for a new drug entity, determination of influence of excipients, patient related factors & possible interaction with other drugs on the efficiency of absorption, development of new formulations of the existing drugs, control of quality of a drug product during the early stages of marketing in order to determine the influence of processing factors, storage & stability on drug absorption

1. M.Pharm 2 nd Semester Seminar Subject : Biopharmaceutics Topic : Methods F or D etermination Of Bioavailability By: Anindya Jana M.Pharm 1 st 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 Plasma Drug Concentration Time for the peak plasma (blood) concentration (t max ). Peak Plasma drug concentration (C max ). Area under the plasma drug concentration-time curve (AUC). Urinary Drug Excretion Cumulative amount of drug excreted in the urine (D u ). Rate of drug excretion in the urine (dD u /dt). Time for maximum urinary excretion (t). Acute Pharmacodynamic Effect Maximum Pharmacodynamic Effect (E max ) Time for maximum pharmacodynamic effect. Area under the pharmacodynamic effect-time curve. Onset time for pharmacodynamic effect. Clinical Observations Well controlled clinical trial. 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. Time For The Peak Plasma (Blood) Concentration (t max ) : It is the time required to reach maximum drug concentration after drug administration. The t max can be used as an approximate indication of drug excretion rate. Peak Plasma Drug Concentration (C max ) : Represent the maximum plasma drug concentration obtained after oral administration of drug. C max provides indications that the drug systemically absorbed to provide a therapeutic response. 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. Cumulative Amount of Drug Excreted In The Urine (D u ) : It is related directly to the total amount of drug absorbed. Rate of Drug Excretion In The Urine (dD u /dt) : Rate of drug excretion is dependant on first order elimination rate constant k and the concentration of drug in the plasma C p . Time For Maximum Urinary Excretion (t) : It is analogous to the t max 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 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. 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 Shargel L, Pong S, Yu A; Bioavaibility & Bioequivalence; Applied Biopharmaceutics & Pharmacokinetics; Published By Mc Graw Hill; 2005; P 460-464 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

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