bioavailability

Views:
 
Category: Education
     
 

Presentation Description

No description available.

Comments

Presentation Transcript

A seminar on bio-availability:

A seminar on bio-availability PRESENTED BY Saiesh phaldesai

BIO AVAILABILITY:

BIO AVAILABILITY BIO AVAILABILITY the measure of rate and extent of drug reaches the systemic circulation in its unchanged form following the administration of a dosage form

PURPOSE OF BIOAVAILABILITY:

PURPOSE OF BIOAVAILABILITY For marketing approval of new drug, FDA meets bioavailability studies Establish the pharmacokinetic characters and it is useful in establish dosage regimens Bio availability studies are useful in determining the safety, efficacy, identity, strength, quality and purity of the drug product

MEASUREMENT OF BIO AVAILABILITY:

MEASUREMENT OF BIO AVAILABILITY Divided in to three categories. Pharmacokinetic method Pharmacodynamic method scientgraphy study Selection of method depends on the: Purpose of the study Analytical method of drug measurement Nature of the drug product

PHARMACOKINETIC METHOD :

PHARMACOKINETIC METHOD It is also called as Indirect method Plasma level-time studies Urinary excretion studies

PLASMA LEVEL-TIME STUDIES:

PLASMA LEVEL-TIME STUDIES PRINCIPLE : It is based on the assumption that two dosage forms that exhibit super imposable plasma level time profile in a group of subjects should result in identical therapeutic activity

FOR SINGLE DOSE STUDY:

FOR SINGLE DOSE STUDY It requires collection of serial blood samples for a period of 2 to 3 biological half lives, after drug administration And then analysis for drug concentration By making a plot of concentration vs corresponding time of sample collection to obtain plasma level time profile

FOR MULTIPLE DOSE:

FOR MULTIPLE DOSE Method involves drug administration for at least 5 biological half lives A blood sample should be taken at the end of previous dosing interval and 8 to 10 samples after the administration of next dose

PARAMETERS:

PARAMETERS 3 parameters of these method used to estimate the bio availability are: Cmax : Peak plasma concentration. Tmax : Peak time AUC : Area under the plasma level- time curve

PowerPoint Presentation:

Time t max C MAX PLASMA CONC PLASMA DRUG LEVEL-TIME CURVE

MEASUREMENT OF AUC:

MEASUREMENT OF AUC 1)PHYSICAL METHODS A)CUT AND WEIGHT METHOD B)PLANIMETER 2)TRAPEZOIDAL METHOD 3)INTEGRATION METHOD

PowerPoint Presentation:

RELATIONSHIP BETWEEN AUC AND DOSE AUC Dose AUC Dose

CUT & WEIGH AND PLANIMETER METHODS :

CUT & WEIGH AND PLANIMETER METHODS CUT & WEIGH : Plasma concentration profile are plotted on smooth paper, these can be cut out and weighed and the weight of the papers is directly proportional to AUC PLANIMETER : A planimeter is a percision instrument which allows the calculation of areas by tracing there outlines

TRPEZOIDAL METHOD:

TRPEZOIDAL METHOD It involves the breaking up of the plasma con vs time profile in to several trapezoids calculating the area of each trapezoid and add them to obtain the AUC AUC = [(c o +c 1 )(t 1 -t o )/2]+……… + (c n-1 +c n )(t n -t n-1 )/2

INTEGRATION METHOD:

INTEGRATION METHOD AUC=A(1/K e -1/K a ) where K e =overall elimination constant K a =absorption constant

EXTENT OF BIOAVAILABILITY FOR SINGLE DOSE STUDY:

EXTENT OF BIOAVAILABILITY FOR SINGLE DOSE STUDY F=[AUC] oral D iv / [AUC] iv D oral F r =[AUC] test D std / [AUC] std D test D = DOSE ADMINISTERED

EXTENT OF BIOAVAILABILITY FOR MULTIPLE DOSE STUDY:

EXTENT OF BIOAVAILABILITY FOR MULTIPLE DOSE STUDY F r =[AUC] test D std T test / [AUC] std D test T std T=Dosing interval Bioavailability can also be measured by peak plasma concentration at steady state, F r =[C ssmax ] test D std T test /[C ssmax ] std D test T std T=dosing interval

URINARY EXTRECTION STUDIES:

URINARY EXTRECTION STUDIES PRINCIPLE : It involves urinary excretion of unchanged drug is directly proportional toplasma concentration of drug Eg : thiazide diuretics, sulphonamides For drugs that have urine as site of action eg: urinary antiseptics : nitrofurantoin.

METHOD FOR URINARY EXCRETION STUDIES:

METHOD FOR URINARY EXCRETION STUDIES It involves collection of urine at regular intervals for a time span equal to 7 biological half lives Then analysis for unchanged drug in the collected sample Then determined the amount of drug excreted in each interval and cumulative amount excreted

PARAMETERS:

PARAMETERS (d xu /dt) max : Max urinary excretion rate. (T u ) max : Time for Max excretion rate. (X u ):Cumulative amount of drug excreted in the urine

PowerPoint Presentation:

E X CR E T I ON URINE COLLECTION PERIOD ( dxu/dt)max (Tu)max URINARY EXCRETION STUDIES

EXTENT OF BIOAVAILABILITY FOR SINGLE DOSE:

EXTENT OF BIOAVAILABILITY FOR SINGLE DOSE F=(X u ) oral D iv /(X u ) iv D oral F r =(X u ) test D std /(X u )D std

EXTENT OF BIOAVAILABILITY FOR MULTIPLE DOSE STUDY AT STEADY STATE:

EXTENT OF BIOAVAILABILITY FOR MULTIPLE DOSE STUDY AT STEADY STATE F r =(X u,ss ) test D std T test /(X u,ss ) std D test T std (X u,ss ) It is the amount of drug excreted in unchanged form during a single dosing interval at Steadystate

ADVATAGES OF URINARY EXCRETION STUDIES:

ADVATAGES OF URINARY EXCRETION STUDIES These method is useful when there is a lack of sufficiently sensitive analytic tech to measure concentration of drugs in plasma with accuracy Convenince of collecting urine samples. Direct measurement of absolute and relative bioavailablity is possible without the neccesity of fitting the data to a mathematic model When coupled with plasma level-time data,it can be used to estimate renal clearance of un changed drug,by CL R =total amount of drug excreted unchanged / AUC

PHARMACODYNAMIC METHOD:

PHARMACODYNAMIC METHOD It is also called as direct method Acute pharmacological response Therapeutic response

ACUTE PHARMACOLOGICAL RESPONSE:

ACUTE PHARMACOLOGICAL RESPONSE Acute pharmacological effect such as change in ECG OR EEG readings,pupil diameter etc is related to the time course of a given drug Bioavailability can be determined: By construction of pharmacologic effect - time curve By dose-response graphs

THERAPEUTIC RESPONSE:

THERAPEUTIC RESPONSE This method is based on observing the clinical response to a drug formulation given to a patient suffering from disease for which it is intended to be used Draw back is difficult assessment of relative bio availability between two dosage forms of the same drug

SCIENTGRAPHY STUDY:

SCIENTGRAPHY STUDY Radioactive substances is used to investigate the extent of absorption of drugs, which are directly introduced to the colon or targeted to colon

REASONS FOR POOR BIO-AVAILABILITY:

REASONS FOR POOR BIO-AVAILABILITY Poor aqueous solubility or slow dissolution rate. Poor stability of the dissolved drug at the physiologic PH Inadequate partition coefficient and thus poor permeation through the bio membrane. Extensive pre-systemic metabolism.

APPROACHES TO ENHANCE THE BIOAVAILABILITY:

APPROACHES TO ENHANCE THE BIOAVAILABILITY THE PHARMACEUTIC APPROACH THE PHARMACOKINETIC APPROACH THE BIOLOGIC APPROACH

METHODS FOR ENHANCEMENT OF BIOAVAILABILITY:

METHODS FOR ENHANCEMENT OF BIOAVAILABILITY MICRONIZATION: Steroidal drugs, sulfa drugs, griseofulvin USE OF SURFACTANTS: Polysorbates increases the bio avaialability of spiranolactone USE OF SALT FORMS : Alkali metal salts of acidic drugs like pencillin, strong acid salts of basic drugs like atropine have more water soluble than parent drug

PowerPoint Presentation:

ALTERATION OF PH OF MICROENVIRONM ENT OF DRUG: by two ways A) In situ salt formation B) addition of buffers eg: buffered aspirin tablets USE OF META STABLE POLYMORPHS : Eg: B- chloramphenicol palmitate is more water soluble than A and C SELECTIVE ADSORPTION ON INSOLUBLE CARRIERS : Bentonite can enhance the dissolution of poorly water soluble drugs such as indometacin,prednisone by two reasons weak physical bonding between adsorbate and adsorbent and hydration, sweeling of clay in aqueous media

PowerPoint Presentation:

SOLID SOLUTIONS : a) use of solid solutions b)use of eutectic mixtures c)use of solid dispersions reduces the particle size by different mechanisms and thus enhances the bioavailability. MOLECULAR ENCAPSULATION WITH CYCLODEXTRIN : the beta dextrins and there derivatives have ability to molecular inclusion complexes with hydro phobic drugs having poor water solubility.the out side of the host molecule have water soluble and thus improves the aqueous solubility and dissolution rate and thus bio availability. Eg: thiazides diuretics

PowerPoint Presentation:

thank you

authorStream Live Help