BIOAVAILABILITY AND BIOEQUIVALENCE TESTING

Presented by N.Lakshmi PriyaPharmaceuticsM.Pharmacy

INTRODUCTIONIntroduced in 1945.

Studies of relative absorption of vitamins.

Referred as physiologic availability.

CONCEPT OF BIOAVAILABILITY?Increased prescriptions.

Formulary systems.

Extending the laws of pharmacist’s role.

By US federal government.

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 =

OBJECTIVES:

suitable dosage form.

efficiency of absorption.

New formulations.

Control of quality

TYPES OF BIOAVAILABILITY

1.Absolute bioavailability

Plasma concentration versus time data

Urinary data

2.RELATIVE BIOAVAILABILITY

Plasma concentration vs time data.

Urinary data

FACTORS AFFECTING BIOAVAILABILITYFORMULATION

FACTORS

EXCIPIENTSNATURE OF THE DRUGPARTICLE SIZEFORM OF THE DRUG

PHYSIOLOGICAL FACTORS

GASTRIC EMPTYINGINTESTINAL MOTILITYPH INTESTINAL WALL

CHANGES

CRITERIA FOR BIOAVAILABILITY TESTING

12 subjects.

Physical examination and laboratory testing.

Cross over design.

MEASUREMENT OF BIOAVAILABILITY

Pharmacokinetic methodsPlasma level time studiesUrinary excretion studiesPharmacodynamic methodsAcute pharmacologic responseTherapeutic response

PHARMACOKINETIC METHODS1.Plasma level time studies3 parameters are to be considered.

Cmax.tmax.AUC

2.URINARY EXCRETION STUDIES.

3 parameters are to be considered.

dXu/dt(tu)maxXU

ACUTE PHARMACOLOGIC RESPONSEECG or EEG, pupil diameter is related to time course of a given drug.

time

Dose

DISADVANTAGESVariable

Difficulty in correlation

Response is not due to the pharmacological effect.

2.THERAPEUTIC RESPONSEClinical response to a given formulation.•Drawback:Quantitation is improper to assess the relative bioavailability.

OTHER MEASURES1.DISSOLUTION RATEIn-vitro dissolution testing models.Factors to be considered.Dissolution apparatusDissolution fluidProcess parameters

TYPES OF DISSOLUTION APPARATUSClosed -compartmentOpen-compartmentDialysis systems ROTATING BASKET ROTATING PADDLE

IN VITRO-IN VIVO CORRELATIONObjectivesBatch to batch consistency developing a new dosage formBasic approaches By linear relations shipBy using previous data

QUANTITATIVE INVITRO-INVIVO CORRELATIONSBased on plasma level dataBased on urinary excretion dataBased on pharmacologic response

STATISTICAL TERMSAverageANOVABar over a letterBioequivalenceConfidence intervalControl Cross overDistributionFormulation

Frequency distributionLogarithmic transformationMeanMedianPeriodSequence groupStandard errorwashout

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

MEASUREMENT OF BIOEQUIVALENCE

Same route,equal doses,different times.Study in healthy, adult male volunteers.

Latin square cross over design

ADVANTAGESMinimises intersubject variability.Minimises variationsMinimises carry over effects.DRAWBACKS Long timeDropout Rates are high

Statistical interpretation of analysis data. ANOVA

CLINICALLY SIGNIFICANT

METHODS FOR ENHANCMENT OF BIOAVAILABILITYMicronizationUse of surfactantsUse of salt formsAlteration of pH of the drug micro environmentUse of metastable polymorphSolute-solvent complexationSolvent deposition

Selective adsorption on insoluble carriersSolid solutionsEutectic mixturesSolid dispersionsMolecular encapsulation with cyclodextrins

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