Bioavailability and bioequivalence testing
Transcript of Bioavailability and bioequivalence testing
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BIOAVAILABILITY AND BIOEQUIVALENCE TESTING
Presented by N.Lakshmi PriyaPharmaceuticsM.Pharmacy
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INTRODUCTIONIntroduced in 1945.
Studies of relative absorption of vitamins.
Referred as physiologic availability.
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CONCEPT OF BIOAVAILABILITY?Increased prescriptions.
Formulary systems.
Extending the laws of pharmacist’s role.
By US federal government.
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DEFINITION:
Relative amount of an administered dose that reaches the systemic circulation. ORRate and extent of absorption of unchanged drug from its dosage form.
bioavailable dose administered dose
F =
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OBJECTIVES:
suitable dosage form.
efficiency of absorption.
New formulations.
Control of quality
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TYPES OF BIOAVAILABILITY
1.Absolute bioavailability
Plasma concentration versus time data
Urinary data
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2.RELATIVE BIOAVAILABILITY
Plasma concentration vs time data.
Urinary data
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FACTORS AFFECTING BIOAVAILABILITYFORMULATION
FACTORS
EXCIPIENTSNATURE OF THE DRUGPARTICLE SIZEFORM OF THE DRUG
PHYSIOLOGICAL FACTORS
GASTRIC EMPTYINGINTESTINAL MOTILITYPH INTESTINAL WALL
CHANGES
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CRITERIA FOR BIOAVAILABILITY TESTING
12 subjects.
Physical examination and laboratory testing.
Cross over design.
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MEASUREMENT OF BIOAVAILABILITY
Pharmacokinetic methodsPlasma level time studiesUrinary excretion studiesPharmacodynamic methodsAcute pharmacologic responseTherapeutic response
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PHARMACOKINETIC METHODS1.Plasma level time studies3 parameters are to be considered.
Cmax.tmax.AUC
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2.URINARY EXCRETION STUDIES.
3 parameters are to be considered.
dXu/dt(tu)maxXU
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ACUTE PHARMACOLOGIC RESPONSEECG or EEG, pupil diameter is related to time course of a given drug.
time
Dose
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DISADVANTAGESVariable
Difficulty in correlation
Response is not due to the pharmacological effect.
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2.THERAPEUTIC RESPONSEClinical response to a given formulation.•Drawback:Quantitation is improper to assess the relative bioavailability.
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OTHER MEASURES1.DISSOLUTION RATEIn-vitro dissolution testing models.Factors to be considered.Dissolution apparatusDissolution fluidProcess parameters
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TYPES OF DISSOLUTION APPARATUSClosed -compartmentOpen-compartmentDialysis systems ROTATING BASKET ROTATING PADDLE
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IN VITRO-IN VIVO CORRELATIONObjectivesBatch to batch consistency developing a new dosage formBasic approaches By linear relations shipBy using previous data
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QUANTITATIVE INVITRO-INVIVO CORRELATIONSBased on plasma level dataBased on urinary excretion dataBased on pharmacologic response
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STATISTICAL TERMSAverageANOVABar over a letterBioequivalenceConfidence intervalControl Cross overDistributionFormulation
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Frequency distributionLogarithmic transformationMeanMedianPeriodSequence groupStandard errorwashout
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BIOEQUIVALENCEDrug substance in two or more identical dosage forms reaches the systemic circulation at same relative rate and extent.
RELATED TERMS
Pharmaceutical equivalenceChemical equivalenceTherapeutic equivalence
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MEASUREMENT OF BIOEQUIVALENCE
Same route,equal doses,different times.Study in healthy, adult male volunteers.
Latin square cross over design
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ADVANTAGESMinimises intersubject variability.Minimises variationsMinimises carry over effects.DRAWBACKS Long timeDropout Rates are high
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Statistical interpretation of analysis data. ANOVA
CLINICALLY SIGNIFICANT
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METHODS FOR ENHANCMENT OF BIOAVAILABILITYMicronizationUse of surfactantsUse of salt formsAlteration of pH of the drug micro environmentUse of metastable polymorphSolute-solvent complexationSolvent deposition
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Selective adsorption on insoluble carriersSolid solutionsEutectic mixturesSolid dispersionsMolecular encapsulation with cyclodextrins
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REFERENCESBiopharmaceutics and pharmacokinetics-D.M BRAHMANKAR. Page no:282-302Biopharmaceutics and pharmacokinetics-P L MADHANPage no:125-178Basic pharmacokinetics-SUNIL S JAMBHEKAR AND PHILIP J BREEN page no:458-470