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Bioavailability & Bioequivalence Studies

Bioavailability & Bioequivalence Studies
https://youtube.com/vishalshelke99
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Sub :- Research Methodology
M.Phrmacy Semister 1
Savitribai Phule Pune University

Bioavailability:
Bioavailability is defined as a measure, of the rate and amount of drug, which reaches the systemic circulation unchanged following the administration of a dosage form.

Absolute bioavailability:
When systemic availability of a drug administered orally
is determined in comparison to its I.V. administration, denoted by F.

Relative bioavailability:
When systemic availability of a drug after oral administration is
Compared with that of oral standard of the same drug
( Solution or suspension ) and denoted by Fr.

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Bioavailability & Bioequivalence Studies

  1. 1. Presentation on Bioavailability & Bioequivalence Studies Presented By :- Vishal Shelke M.Pharm – I Guided By :- R. Chavan Department of Pharmaceutics PDEA’s SGRS College of Pharmacy Saswad
  2. 2. Contents :-  Definitions  Objectives of Bioavailability studies  Methods of Bioavailability measurement -- Pharmacokinetic methods: -- Pharmacodynamic methods:  Bioequivalence experimental study designs 1. Completely randomized designs 2. Randomized block designs 3. Repeated measures, cross over, carry-over designs 4. Latin square designs
  3. 3. Bioavailability: Bioavailability is defined as a measure, of the rate and amount of drug, which reaches the systemic circulation unchanged following the administration of a dosage form. Absolute bioavailability: When systemic availability of a drug administered orally is determined in comparison to its I.V. administration, denoted by F. Relative bioavailability: When systemic availability of a drug after oral administration is Compared with that of oral standard of the same drug ( Solution or suspension ) and denoted by Fr.
  4. 4. Objectives of Bioavailability Studies :- It is important in the  Primary stages of development of dosage form of new drug entity to find its therapeutic utility.  Determination of influence of excipients on absorption.  Development of new formulations of existing drugs.  Control of quality of drug products and influence of processing factors , storage and stability on absorption.  Comparison of drug in different dosage forms or same dosage form of different manufacturer.
  5. 5. Methods of Bioavailability Measurement :- Phamacokinetic Method 1. Plasma level time studies: most reliable method of choice comparison to urine data method Single dose: serial blood samples collection – 2-3 half lifes Plot concentration vs time graph • For I.V. Sampling started within 5 min and subsequent samples at 15min intervals • For oral dose at least 3 points taken on absorption curve ( ascending part)
  6. 6. Parameters considered important in plasma level time studies 1. Cmax : It is peak plasma concentration. It increases with dose as well as increase in rate of absorption. 2. Tmax: The peak time at which Cmax atended. 3. AUC: Area under curve explains about amount of drug.
  7. 7. 2. Urinary excretion studies: This method is based on the principle that the urinary excretion of unchanged drug is directly proportional to the plasma concentration of drug. It can be performed if - At least 20% of administered dose is excreted unchanged in urine. - Drugs that extensively excreted unchanged in urine eg. Thiazide diuetics - Drugs that have urine as site of action eg. Urinary antiseptics like nitrofurontoin. Steps involved : • collection of urine at regular intervals for 7 half lifes. • Analysis of unchanged drug in collected sample. • Determination of amount of drug at each interval and cumulative as well. Following Criteria's must be followed • At each sample collection total emptying of bladder is necessary. Frequent sampling is essential in the beginning to compute correct rate of absorption. • The fraction excreted unchanged in urine must remain constant.
  8. 8. 1. Acute pharmacological response: When bioavailability measurement by pharmacokinetic methods is difficult, inaccurate or non reproducible this method is used. Such as ECG, Pupil diameter etc. It can be determined by dose response graphs. Responses measure for at least 3 half lifes. 2. Therapeutic response: This method is based on observing clinical response in patients. Drawbacks : - The physiological status of subject assumed that does not change significantly over duration of study. - If multiple dose protocols are not involved. Patient receive only single dose for few days or a week - The patient s receiving more than one drug treatment may be compromised due to drug-drug interaction. Pharmacodynamic methods
  9. 9. Bioequivalence Studies It is a relative term which denotes that the drug substance in two or more identical dosage forms, reaches the systemic circulation at same relative rate and relative extent. Types of Bioequivalence studies : 1. In Vivo Bioequivalence studies 2. In Vitro Bioequivalence studies
  10. 10. In Vivo Bioequivalence studies :- The following sequence of criteria is useful in assessing the need for in vivo studies. a. Oral immediate release products with systemic action - Indicated for serious conditions requiring assured response. - Narrow therapeutic margin. Unfavourable physiochemical properties e.g., Low solubility, meta stable modifications, instability etc. b. Non Oral immediate release products c. Modified release products with systemic action.
  11. 11. 2. In Vitro Bioequivalence studies :- In comparative in vitro dissolution studies. In vivo bioequivalence under certain circumstances called as biowaivers The drug product differs only in strength of the active substances it contain, provided all the following conditions hold- • The drug product has been slightly reformulated method has been slightly modified. • The drug product is in the form of solution or solubilised form (eg., elixir, syrup, tincture etc., • In vitro dissolution rate of the new products is equivalent with that of the already approved medicinal product. Topical administration (Cream, ointment gel) for local effect. Oral administration but intended to be absorbed.
  12. 12. Bioequivalence Experimental study design: 1. Completely randomisation 2. Randomised block designs 3. Repeated measures, cross over and carry over designs 4. Latin square designs 1. Completely randomisation In a completely randomised design, all treatments are randomly allocated among all expermental subjects. Method of Randomisation: Subject with the same number of digits Advantages: The design is extremely easy to construct Accommodate number of treatments and subjects. Disadvantages: The situations in whcih there are relatively few treatments .
  13. 13. 2. Randomised block design :- First subject are homogenous groups called blocks and the treatments are then assigned at random with in the blocks. Method of Randomisation:- Subjects having back ground characteristics are found as blocks. Advantages: Accomodate any number of treatments Treatment need not have equal sample size Statistical analysis is relatively simple. Disadvantages: Missing observations with in a block require more complex analysis. The degree of freedom of experimental error are not a large.
  14. 14. 3. Repeated measures :- cross over and carry over designs The Randomised block design in which the same subject serves as a block. The administration of two or more treatments one after the other in a specified order to the same group of patients is called a cross over design. To prevent carry over effect one must always allow for a wash out period during which most of the drug is eliminated form the body generally about 10 elimination half lives. Example: Clinical trials to monitor safety and side effects.
  15. 15. Method of Randomisation. Complete randomisation is used to randomise the order of treatments for each subject. Advantage: It provides good precision for comparing treatments because variability b/w subjects. It is economic on subjects. The interest in the effects of a treatment over time, it is easy to observe the same subject at different points. Disadvantage: There may be an order effect, which is connected with the position in the treatment order. There may be a carry over effects, which is connected with the preceding treatment.
  16. 16. 4. Latin square designs :- Completely randomised design, randomised block design and repeated measures design are experiments where the person / subject / volunteer remains on the treatment from the start of the experiments untill the end are called as continuous trail. A latin square design is a two factor design with one observation in each cell. A latin square is called standard if the first row add the first column consist of the r letters in alphabetical order.
  17. 17. References :- 1. Biopharmaceutics and pharmacokinetics – A Treatise, D. M. Brahmankar, Sunil B.Jaiswal. Vallabh prakashan IInd edition 315-366 2. Internet Sources
  18. 18. Also available on Youtube Youtube :- https://youtube.com/vishalshelke99 Instagram :- https://instagram.com/vishal_stagram
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