Bioavailability and bioequivalence testing
Transcript of Bioavailability and bioequivalence testing
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