BIBD study

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Design of Be study

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BIOequivalence STUDY DESIGN :

BIOequivalence STUDY DESIGN BY SHILPA.B M.PHARM PHARMACEUTICS SRM College Of Pharmacy, Chennai

STUDY DESIGN :

STUDY DESIGN Various factors have to be considered in conducting bioavailability study since the rate and absorption of a drug in to the systemic circulation , its distribution and elimination are influenced by many factors such as age , sex , body weight and experimental design etc.

PARALLEL DESIGN:

PARALLEL DESIGN The aim of this experimental design is to minimize the experimental variables and to avoid the bias. In parallel design 2 formulations are administered to 2 groups of volunteers . To avoid the bias , formulations are administered randomly to the volunteers The major disadvantage of this design is that the inter subject variation is not being corected

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Therefore a cross over design is preferred in bioavailability study to avoid the inter subject variation

CROSS OVER DESIGN :

CROSS OVER DESIGN This minimizes the effect of inter subject variability in the study by using each subject as his or her own control Generally 2 types of design are used in bioavailability trials . They are 1) L atin square design 2) BIBD

LATIN SQUARE DESIGN :

LATIN SQUARE DESIGN In the design Each formulation is administered just once in each study period Each subject receives just once each formulation There are 3 designs a) 2 way cross over design b) 3 way cross design c) 4 way cross over design

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In a 2 way design 12 subjects are used to study the bioequivalency study of 2 formulations (treatment A and B) During the 1 st study period subjects 1-6 treatment A and 7-12 treatment B . A second study period is initiated after the wash out period , during which a complete elimination of the drug and its metabolites takes place

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In the second study period subjects 1-6 now receives treatment B and 7-12 treatment A. Therefore each subject acts as his or her own control.

ADVANTAGES :

ADVANTAGES It minimizes the effect of inter subject variability Minimizes the carry over effects Minimizes the time effect on bioavailability since each dosage form is administered in each study period It requires less number of subjects

DISADVANTAGES :

DISADVANTAGES Requires longer time to complete the study since a wash out period exists between 2 study periods. High biological half life , longer time to complete the study The time to complete the trail depends on the number of formulations evaluated in the study Increase in number of study periods leads to high subject drop outs and the study becomes difficult

2 WAY CROSS OVER DESIGN:

2 WAY CROSS OVER DESIGN GROUP NUMBER SUBJECTS IN GROUP TREATMENT FOR PERIOD NUMBER I II 1. 1,2,3,4,5,6 A B 2. 7,8,9,10,11,12 B A

3 WAY CROSS OVER DESIGN:

3 WAY CROSS OVER DESIGN GROUP NUMBER SUBJECTS IN GROUP TREATMENT FOR PERIOD NUMBER I II III 1. 1,2,3,4,5,6 A B C 2. 7,8,9,10,11,12 B C A 3. 13,14,15,16,17,18 C A B

4 WAY CROSS OVER DESIGN:

4 WAY CROSS OVER DESIGN GROUP NUMBER SUBJECTS IN GROUP TREATMENT FOR PERIOD NUMBER I II III IV 1. 1,2,3,4,5,6 A B C D 2. 7,8,9,10,11,12 B D A C 3. 13,14,15,16,17,18 C A D B 4. 19,20,21,22,23,24 D C B A

BALANCED INCOMPLETE BLOCK DESIGN:

BALANCED INCOMPLETE BLOCK DESIGN Salient features of this design are 1) each subject receives not more than 2 formulations 2) each formulation is administered the same number of times 3) each pair of formulations occur together in the same number of subjects

BIBD:

BIBD SUBJECT TREATMENT PERIOD NUMBER I II 1. A B 2. B A 3. A C 4. C A 5. A D 6. D A 7. B C 8. C B 9. B D 10. D B 11. C D 12. D C

WASH OUT PERIOD :

WASH OUT PERIOD In a latin square cross over study deign each subject receives each formulation even in BIBD each subject receives 2 formulations at different occassions . The time interval between 2 treatments is called wash out period Wash out period is required for the elimination of the drug to avoid the carry over effects

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A period of atleast 10 half lifes should be allowed between the treatments. This should ensure an elimination of 99.9% dose and carry over less than 0.1% from the 1s treatment.

DRUG PRODUCTS :

DRUG PRODUCTS Test product : This may be a new drug formulation developed by a technologist a new dosage form of an existing drug . A test product may be compared to the reference std recognised by the FDA for getting approval for marketing the drug product These are evaluated because

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1) to select the best dosage form 2) to select the best formulation 3) to compare the biological performance of a test product to that of the std

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R eference standard : In general FDA accepts any innovators drug product as a std The innovator is the one who originally receives approval from the FDA to market the product in the country Therefore any one of the permitted drug product can be used as a reference std

ROUTE OF ADMINISTRATION :

ROUTE OF ADMINISTRATION Orally administered dosage forms are subjected for bioavialability studies. Dosage forms administered by other routes such as buccal , transdermal , intramuscular should also be evaluated for their biological performance . Orally administered dosage forms show a much variation in their performance because of inter and intra subject variations

SINGLE VERSUS MULTIPLE DOSE STUDY DESIGN :

SINGLE VERSUS MULTIPLE DOSE STUDY DESIGN If the dosage forms are to be evaluated only for bioequivalence purposes, single dose studies are usually sufficient . This is because the relative bioavailability of most tablets and capsules can be determined on a single dose basis . Dosage forms which are meant for a single dose administration of a therapeutic benefit such as analgesics for the relief of headache need only single dose study

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Timed release preparations , drugs that undergo first pass metabolism , enteric coated – multiple dose study

ADMINISTRATION OF DRUG PRODUCTS :

ADMINISTRATION OF DRUG PRODUCTS It is based on randomization . After administration blood samples are withdrawn from the subjects at fixed time points . It takes some time to take a sample from each subject and the total time difference between 1 st subject and last subject may range from 10-20 min

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If the sampling schedule is not followed that leads to difference in the actual duration of drug in the body. To avoid this type of effect randomized administration of drug products is used.

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GROUP NUMBER SUBJECTS IN GROUP TREATMENT FOR PERIOD NUMBER I II III 1. 1,2,3,4,5,6 A B C 2. 7,8,9,10,11,12 B C A 3. 13,14,15,16,17,18 C A B

SAMPLING :

SAMPLING If the bioavailability of the given dosage form is to be evaluated by blood level study Some estimate of the area under the serum concentration vs time curve , peak serum concentration and the time of peak serum concentration must be obtained from the study Therefore the frequency of sampling and duration of sampling are very important

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The sampling scheme should be frequent enough to define the absorption phase , the peak , elimination phase during a drugs time course in the body In order to estimate the rate of absorption it is necessary to have enough data point in the absorption phase In case of urinary excretion studies same principles apply

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These are used when it is not possible to measure a given drug in the blood , plasma , serum . Advantages : Involves non invasive method of sampling Concentration of drug in urine greater that in blood / serum allowing easy estimation o f drug Amount of drug excreted in urine is obtained directly

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Disadvantages : Not useful in estimating the absorption rate of a rapidly absorbing drug Metabolites are also concentrated in the sample that interferes with the estimation of unchanged drug in urine

SELECTION OF SUBJECTS :

SELECTION OF SUBJECTS Healthy subjects vs patients : Bioavailability studies are designed to find out the dosage form biological performance . So it is to minimize all possible variatons problems associated with testing in patients are It is difficult to obtain many patients in a given place The severity of a disease varies from one to another patient Ethical considerations do not allow withdrawal of many blood samples from the patients for a longer time

STUDY CONDITION :

STUDY CONDITION The selected subjects to be maintained on uniform diet and none of them should have taken any drug atleast 1 week prior to the study Fasting period before administration , time period after drug product administration during which fasting is continued to be defined during the study

ANALYSIS OF BIOLOGICAL SAMPLES :

ANALYSIS OF BIOLOGICAL SAMPLES Biological samples collected as per the sampling procedure have to be analysed immediately after the study Samples are stored for several days before they are subjected to chemical analysis . Storage of these samples is an important aspect since during storage , the sample may undergo chemical degradation , absorption on to the wall of the container.

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Non specific analytical methods used are less desirable If the method used is non specific then the results of the study may not relieve the difference in therapeutic efficacy that exists between the 2 drugs Only 1 analytical method should be used for all the samples of the study Analytical method used must be specific to the active chemical moiety and should exhibit high sensitivity.

THANK YOU:

THANK YOU

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