Bioavailability & bioequivalance


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Bioavailability & bioequivalance

  2. 2. BIOAVAILIBILITYBIOAVAILIBILITY ??Is the rate and extent (amount) of absorption ofunchanged drug from its dosage form.Bioavailable fraction: administered dose that entersthe systemic circulationf = bioavailable doseadministered dose
  3. 3. Objectives:-Development of a suitable dosage formDevelopment of new formulationControl of quality of a drugInfluence of recipients , patient related factors ,interaction with other drugs
  4. 4. Types Of BioavailabilityAre of 2 types:- Absolute bioavailabilitysystemic availability of a drug administered orally isdetermined in comparison to its intravenousadministration Relative bioavailabilitysystemic availability of a drug after oraladministration is compared with that of the samedrug
  5. 5. Methods of enhancingbioavailabilityMicronizationUse of surfactantsUse of salt formsSelective adsorption on insoluble carriersSolvent deposition
  6. 6. Above graph shows the comparison of drugconcentration in blood due to different dosageforms
  7. 7. BIOAVAILABILITY STUDIESSingle dose vs. multiple dose studiesRequires collection of fewer blood samplesBetter evolution of control released drug is possibleMore accurateLess sensitive analytical method can be used
  8. 8. Healthy human subjects vs.patientsAdvantages of patient Advantagesof healthy subjects1. Benefit 1.Standard of drugs2.Therapeutic efficacy3.Drug absorptionDrawbacks of patients1. Drug absorption modify
  9. 9. Measurement Of BioavailabilityStudies1.> Pharmacokinetic methods 1.plasma level time studies 2. urinary excretion studies2.>Pharmacodynamic methods 1.acute pharmacologic response 2.therapeutic response3.>in vitro studies
  10. 10. Pharmacokinetic studiesPlasma level time studies PrincipleThe plama level time profile of a perticular drug will not superimpose by the other drug profile thus result in identical therapeuticresponse.There are three parameters used in plasma time studies:-1. Cmax, 2. Tmax & 3. AUCMethodologysingle dose study multiple dose study1. collection of blood samples 1. collection of blood samplesfor 2-3 half lives after drug for at least 5 half livesadministration2. analysis of drug concentration3. plotting of graph b/w conc. Ofdrugs and time
  11. 11. Urinary excretion studiesPrinciple urinary excretion of unchanged drug is directlyproportional to the plasma concentration of drug studies is carried for extensively excretedunchanged drugs in the urine methodology collection of urine samples at regular intervals for 7biological half lives analysis of unchanged drug inthe sample total emptying of bladder is necessary parameters used are (dx/dt)max , (tu)max , xu
  12. 12. Pharmacodynamic studiesAcute pharmacologic response This Include ECG readings, pupil diameter is relatedto time course of a given drug.Pharmacologic effect –time curve is usedAt least 3 biologic half lives are takenTherapeutic responseObserving the clinical response to a drug formulationgiven to patients
  13. 13. In vitro studiesFor this dissolution studies is doneRotating paddle apparatus is usedDrug is dissolved in 250ml of aqueous media at phof 1-7.5Speed of paddle should be 100 rpmMedia used having ph-6.8,in 0.1n hclTemperature 37 degree Celsius.
  14. 14. BioquivalenceRelative term which denotes that the drug substancein 2 or more identical dosage forms ,reaches thesystemic circulation at the same relative rate and tothe same relative extent
  15. 15. ObjectivesShould be done for the comparison of the 2medicinal products having the same activesubstanceIn order to ensure clinical performance of suchdrugs.Cases where bioequivalence studies notrequired drug is gas drug is administered parentally drug is in form of inhalation
  16. 16. Bioquivalence studiesTerms used in bioequivalence studiesBioequivalenceChemical EqivalencePharmaceutical equivalentsTherapeutic equivalents
  17. 17. Methods used in bioquivalencestudiesPharmacokinetic methodsPharmacodynamic methodsIn –vitro studiesLatin square design cross over
  18. 18. Cross over latin designA crossover study (also referred to as a crossovertrial) is a study in which subjects receive asequence of different treatments (or exposures). crossover studies can be observational studies,many important crossover studies are controlledexperiments.crossover designs have "balance", which meansthat all subjects should receive the same number oftreatments and that all subjects participate for thesame number of periods
  19. 19. AdvantagesMinimizes intersubject variabilityMinimizes the variations due to time effect.DisadvantagesTakes a long timeStudy becomes difficult when there are number offormulations to be tested
  20. 20. Documentation for conduction ofDocumentation for conduction ofstudistudiesesDetails of analytical method validationComments of chief investigator regarding the dataClinical data according to GCPAnalytical data of volunteer plasma samplesCopy of final report
  21. 21. Study reportTable of contentsTitle of studyName of responsible investigatorSite of the studyDates and period in which trials are conductedName and batch number of productsResults of pharmaceutical testsDemographic data of subjectsNames and address of subjectsDetails of dropout and withdrawal of subjectsReports of protocol violationsDetails of how pharmacokinetic parameters werecalculatedDocuments related to statistical analysis
  22. 22. Facilities for conducting the studiesThe study site must have the followingAn investigatorClinical pharmacological unitQualified and trained personnel to performthe followingData handling and interpretationDocumentation and report preparationLaboratory managementQuality assurance of all operations in the centre
  23. 23. Maintainance of recordsShould be maintained by the sponsor for atleast 2years after the expiration of batch of drugRetention OF BA/BESamplesShould be retained by organization for period of 3years after the completion of studies or 1 year afterthe expiration of batch ,whichever is early.
  24. 24. Thank you....