7/31/2019 F. Y. Biopharmaceutics
1/32
BIOPHARMACEUTICS
Biopharmaceutics
It is defined as the study of various factors influencing the rate andamount of drug that reaches the systemic circulation and the use ofthis information to optimize the therapeutic efficacy of drug products.
Biopharmaceutics aspect involves the pharmacokinetic andpharmacodynamic studies of drug.
Pharmacokinetic deals with absorption , distribution , metabolismand elimination of drug and thus determines the effective drug level inbody fluid and tissues.
Pharmacokinetics deals with induction of drug action as a functionof concentration of drug in the body.
Following steps are involved to elicit the pharmacological action.
Drug release
Dissolution of drug
Absorption of drug in systemic circulation
Reaching the drug at site of action
Maintainace of adequate conc. at site of action
7/31/2019 F. Y. Biopharmaceutics
2/32
PROCESSINVOLVEDINDRUGTHERAPY Drug therapy and administration can be divided into four processes.
1. Pharmaceutical Phase
Physiochemical properties of drug
Design & manufacturing of dosage form
2. Pharmacokinetic phase (what body does to drug)
Concerned with ADME of drug
Plasma drug concentration time profile
Its relationship with the dose , dosage form, dosing frequency and route of
administration Relates changes in concentration of drug within the body with time
after administration
3.Pharmacodynamics phase ( what drug does to body)
Concerned with biochemical & physiological effects of drug and itsmechanism of action
It is characterized by the concentration of drug at the site of action & itsrelation to the magnitude of effects observed.
Relates response to concentration of drug in the body
4. Therapeutic Phase :-
Concerned with the translation of pharmacological effect into clinical
benefit
7/31/2019 F. Y. Biopharmaceutics
3/32
7/31/2019 F. Y. Biopharmaceutics
4/32
7/31/2019 F. Y. Biopharmaceutics
5/32
SCHEMATICREPRESENTATIONOF PHARMACOKINETICPROCESS
7/31/2019 F. Y. Biopharmaceutics
6/32
ADME ABSORPTION:
The process of movement of unchanged drug from its site of administration tothe systemic circulation is called absorption.
BIOAVAILABILITY It is defined as the rate and extent (amount) of drug absorption and
availability from the site of action. The concentration of drug in the plasmaand hence its onset of action ,intensity and duration of response depends uponthe bioavailability of drug from its dosage form.
DISTRIBUTION
The movement of drug between one compartment to other( generally bloodand the extravascular tissue) is referred as distribution.
ELIMINATION
The process that tends to remove the drug from the body and terminate itsaction is known as elimination
Metabolism (Biotransformation)
Inactivation of drug due to its conversion from one chemical form to anotheris called metabolism
Excretion
The process of the removal of the drug or its metabolite from the body bydifferent routes is excretion.
7/31/2019 F. Y. Biopharmaceutics
7/32
IMPORTANT DEFINITIONS
Biological Half Life:
It is the time required for the drug concentration in the blood or
plasma to reduce by half its original concentration.
o Bioequivalence:
o It is the comparison of bioavailability of differentformulations or drug products of different manufacturersor
different batches of the same drug product of same strength.o Bioavailable Dose:
o The fraction of the administered dose of the drug that reaches
the systemic circulation in unchanged form is known as
bioavailable dose. (Exception prodrug)o An administered dose will be 100% bioavailable only if the drug
is completely released from the dosage form into GI fluids.
7/31/2019 F. Y. Biopharmaceutics
8/32
ABSORPTION
Drug absorption is defined as the process of movement of
unchanged drug from the site of administration to systemic
circulation. It excludes the drug that is metabolized orchemically changed at the site of application, at site of drug
release or in the membrane.
It is difficult to measure conc. of drug at site of administration.
So it can be measured in plasma more accurately.
Correlation between plasma concentration of drug and
therapeutic response. Thus
Absorption can be defined as the process of movement of
unchanged drug from the site of administration to the site of
measurement i.e. plasma.
7/31/2019 F. Y. Biopharmaceutics
9/32
SIGNIFICANCEOFRATEANDEXTENTOFABSORPTIONINDRUGTHERAPY
Drug completely but slowly absorbed may fail to show
therapeutic response as the plasma conc. for desired effectnever achieved.
Rapidly absorbed drug attains the therapeutic level easily toelicit pharmacological effect.
7/31/2019 F. Y. Biopharmaceutics
10/32
MECHANISMOF DRUG ABSORPTION
1. Active transport
2. Passive transport
3. Facilitated diffusion
4. Pinocytosis / Endocytosis 5. Ion-Pair absorption
6. Convective pore transport
7/31/2019 F. Y. Biopharmaceutics
11/32
MECHANISMOF DRUG ABSORPTION
1. Passive diffusion: It involves the transport of drug from
region of higher concentration in the GI tract to lowerconcentration in the blood. When drug reaches to bloodcirculation , it is continuously removed from the site ofabsorption, maintaining the high concentration gradient.
No energy is utilized so called as passive diffusion.
Small lipid soluble drug can easily cross the membrane thanbig polar molecules.
Low molecular weight polar molecule can pass GI membranethrough water filled pores in the bilayer.
Passive diffusion is governed by Ficks law. -dC/ dt = Ka [C1-C2]
but C1>> C2
-dC/ dt = Ka. C1
7/31/2019 F. Y. Biopharmaceutics
12/32
ACTIVE TRANSPORT
When the concentration of drug on both the sides ofmembrane becomes same it leads to the state of theequilibrium , which is a limitation of the passive diffusion
It brings transportation against concentration gradient &requires energy.
It requires a carrierwhich may be enzyme or some other
component of cell Carrier protein
Drugs having similar structure with amino acids ,essential nutrients, vitamins are absorbed by active
transport. Eg. Levodopa structurally similar to amino acids like
tyrosine is absorbed by active transport
7/31/2019 F. Y. Biopharmaceutics
13/32
7/31/2019 F. Y. Biopharmaceutics
14/32
7/31/2019 F. Y. Biopharmaceutics
15/32
7/31/2019 F. Y. Biopharmaceutics
16/32
FACILITATED DIFFUSION
This is also carrier mediated transport system which
differs from active transport that it can not transport asubstance against a conc. gradient and so occur fro higher
to lower concentration but does not require anexpenditure of energy.
Pinocytosis / Endocytosis
Only mechanism here material does not have to be in
aqueous solution in order to be absorb. It involves the
engulfing of extracellular solids (phagocytosis ) or liquids
(pinocytosis) within a segment of the cell membrane to form
vacuoles containing the material which then cross the
membrane. Macromolecules like proteins are absorbed by
this method
7/31/2019 F. Y. Biopharmaceutics
17/32
7/31/2019 F. Y. Biopharmaceutics
18/32
IONPAIRABSORPTION
Drug ion interact with organic ions of opposite charge to
form an absorbable neutral form which undergo passive
diffusion. Eg. Drugs like quaternary compounds, tetracycline
These are ionized over entire GIT range.
Are lipid insoluble
Water soluble drugs are too large to pass through pore orchannel so ions of these interact with organic ions of
opposite charge to form an absorbable neutral form which
undergo passive diffusion.
CONVECTIVE PORE TRANSPORT Very small molecules like water, urea, low molecular wt sugars & organic
electrolytes cross the cell membranes through aq. filled channels or pores
Pore radius 0.4 nm.
7/31/2019 F. Y. Biopharmaceutics
19/32
FACTORSAFFECTING ABSORPTION
1. Physiological factors
2. Physicochemical factors
3. Dosage form consideration
1. Physiological factors
Anatomy of GIT or surface area GIT- pH
Gastric emptying rate
Gastro intestinal motility/ peristalsis
Interaction of drug within the component of GIT
Dietary factors
7/31/2019 F. Y. Biopharmaceutics
20/32
CONT.
2. Physicochemical factors:
Lipid solubility & dissociation constant
Dissolution rate
Particle size and effective surface area
Salt forms
Drug stability and hydrolysis in GIT Surface active agents
Viscosity
Complexation and adsorption
Bulk solubility and solubility in diffusion layer
Crystal form
7/31/2019 F. Y. Biopharmaceutics
21/32
CONT.
3. Dosage form consideration
A) Influence of type of dosage forms Solution>Suspension>Capsules>Compressed
tablet>Coated medicament
B) Influence of Excipient
Diluents, Surface active agents, viscosity enhancers etc.
7/31/2019 F. Y. Biopharmaceutics
22/32
ROUTESOFADMINISTRATIONS
Three major routes of administration are
The Enteral Route:Includes peroral i.e. gastrointestinal , sublingual, buccal
and rectal route
The Parenteral Route
IV, Subcutaneous, IM etc
The Topical Route
skin, eyes or some specific membranes.
7/31/2019 F. Y. Biopharmaceutics
23/32
7/31/2019 F. Y. Biopharmaceutics
24/32
7/31/2019 F. Y. Biopharmaceutics
25/32
DISTRIBUTION Fate of drug after absorption
It is reversible transfer of drug from one location to another
within the body and determines the extent of drug present inblood and tissue fluid.
The rate and extent of drug distribution determines the
onset of action.
Same time it undergoes protein binding and forms complex Distribution of drug varies from tissue to tissue
Drug distributes rapidly in tissues with high blood supply
kidney, liver , heart, lungs
Bound drug can not show pharmacological action Large polar molecules are difficult to distribute
Smaal lipophillic molecules can distribute easily
7/31/2019 F. Y. Biopharmaceutics
26/32
METABOLISMOR BIOTRANSFORMATION
Drug is foreign substance to the body so body always
tries to eliminate it.
It can be eliminated either in unchanged form or
undergoing chemical changes. (insoluble lipid soluble or
non ionizable drug is converted into more polar , water
soluble form that can easily eliminated)
These changes are called as biotransformation or
metabolism.
Metabolites more water soluble and more ionized.
Less capable ofprotein binding
Less toxic
Less capability of being stored in fats.
Less penetrability through the biological membrane so
less pharmacological active
CO
7/31/2019 F. Y. Biopharmaceutics
27/32
CONT..
Phase I reaction: non synthetic like hydrolysis , reduction or
oxidation which form polarfunctional group
Phase II reaction: involves conjugation gluconidation,acetylation, sulfation, etc.
Conjugation: eg. Acetaminophene forms acetaminophene
glucoronide
Oxidation: eg. Amoxaphine oxidation 8- hydroxy Amoxaphine
Hydrolysis:Aspirine Salicylic Acid
Reduction: Nitroglycerine forms dinitroglycerol
7/31/2019 F. Y. Biopharmaceutics
28/32
7/31/2019 F. Y. Biopharmaceutics
29/32
EXCRETION
Excretion terminates the drugs activity
Majority of drug excreted through urine, some of themthrough bile, saliva, sweat.
Poorly absorbing drugs are excreted through feaces.
Volatile substance can be detected in breath.
Oilsoluble drug have comparatively more residencethan polardrug which excretes fast.
PLASMA CONCENTRATION TIME PROFILE
7/31/2019 F. Y. Biopharmaceutics
30/32
PLASMA CONCENTRATION TIME PROFILEDRUGEFFICIENCY & DOSERESPONSECONCEPT
The therapeutic effect of drug is considered as function of
the concetration of drug in blood plasma. Plasma concentration time profile gives information about
attaining and maintaining the optimum concentration of the
drug at the site of action .
P P
7/31/2019 F. Y. Biopharmaceutics
31/32
PHARMACOKINETIC PARAMETERS
Absorption phase : initial rise in plasma conc. is rapiddue to rate of absorption is fast than distribution and
elimination. Continue till achieve Cmax. Ka>Kd>Ke Peak plasma concentration(Cmax) : Highest
concentration of drug achieved in plasma after a single
dose of drug. Ka =Kd=Ke
Elimination phase: After Cmax conc of drug declines Ke> rate of entry of drug in blood
Time of peak concentration (tmax): time required toachieve Cmax.
Area Under Curve: (AUC) It is the total integral area underplasma concetration time profile and is related to the total
amount of drug absorbed into systemic circulation after
administration of single drug.
PHARMACODYNAMIC PARAMETERS
7/31/2019 F. Y. Biopharmaceutics
32/32
PHARMACODYNAMIC PARAMETERS Minimum effective concentration: (MEC)
Minimum concentration of drug in plasma required to produce
the therapeutic effect
Maximum safe concentration: (MSC) minimum toxic conc. (MTC)
Above this concentration toxic effects are produced
Therapeutic Effect :
Concentration between MEC and MSC
Subtherapeutic level:
Concentration below MEC
Therapeutic window: (Therapeutic index)
Ratio of MEC and MSC
Onset of time: Time required to begin pharmacologicalresponse. Onset of action: begining of action
Duration of action: time period forwhich the plasma conc of
drug remains above MEC