1. PRESENTED BY
GANDHI SONAM MUKESHCHANDRA
INDUSTRIAL PHARMACY

2.  1.Aqueous solubility.
 2.Partition coefficient.
 3.Drug stability.
 4.Protein binding.
 5.Molecular size and diffusivity.

3.  Itis an important consideration in its biological performance
as a SDRF.
 Aqueous solubility of a drug exerts its control on the
absorption process in two ways-
1. By influence on the dissolution rate of a compound
which establish the drug concentration in solution and
the driving force for tissue permeation.
2. By its effect on the ability of the drug to penetrate tissues
which is determined in part by its solubility in the tissue.

4.  Dissolutionrate is related to aqueous solubility
which is given by NOYES-WHITNEY’S EQUATION.
dc/dt=KDA.Cs
Where-dc/dt=dissolution rate.
KD=dissolution rate constant.
A= total surface area of drug particle.
Cs=aqueous saturation solubility of drug.

5. Between the time that a drug is administered and the
time it is eliminated from the body.
It diffuse through a variety of biological membranes
that act primarily as lipid like barriers.
The major criteria in evolution of the ability of a drug to
penetrate these lipid membranes is it apparent oil-water
partition co-efficeint, defined as-
K=Co/Cw
Where,Co=equilibrium concentration of all forms of the
drug.
Cw=equilibrium concentration of all forms of in an
aqueous phase.

6.  In
oral dosage forms, loss of drug through acid
hydrolysis or metabolism in GIT.
 A drugin solid state undergoes degradation at much
slower rate than drug in suspension/solution.
 Drugs with low aqueous solubility have low dissolution
rate and usually suffer oral bioavailability problems.
 Aqueous solubility of weak acids and base is governed
by pka value and pH of the medium.

7.  Distributionof drug in to extra space is governed by
dissociation of drug from protein.
 Drug-protein complex acts as reservoir in the vascular
space for sustained drug release to extra vascular tissue for
drug exhibiting high degree protein binding.
 Somedrugs shows higher degree protein binding ex-
Diazepam shows greater than 95% protein binding

8.  Ability of drug to diffuse through membrane is called as
diffusivity, is a function of molecular size.
 In most of polymers, its possible to logD empirically to
some function of molecular size as –
LogD=-Sv log V+Kv=-Sm log M+Km
Where,V=molecular volume
M=molecular weight
Sv,Sm,Kv,Km are constants
value of D is related to size and shapes of drugs.

9.  1. Absorption
 2. Distribution
 3. Metabolism
 4. Elimination and Biological half-life
 5. Side Effects and Safety Considerations

10.  Rate,extent , and uniformity of absorption
are the important factors when considering
sustained release.
 Sincethe rate limiting step in drug delivery
from a sustained release is its release from
dosage form , rather than absorption,a
rapid release is essential if the system is
successful

11.  The distribution of drug in to vascular and
extravascular spaces in the body is an
important factor in its overall elimination
kinetics.
 This influences the formulations of that drug
in to a sustain release, primarily by
restricting the magnitude of release rate and
dose size.

12.  Volume of distribution obeys only one compartment
model
v=dose/Co
where-Co –plasma drug concentration
 Apparent volume of distribution is merely a
propotionately constant that relates the drug
concentration in blood or plasma to the total amount of
drug in the body.

13. For two compartment models
Vss= (1+ k12/k21)V1
where k12-rate constant for distribution of
drug from central to peripheral
compartment
k21-peripheral to central
Vss-drug concentration in blood or
plasma at steady state to the
total amount of drug

14.  If the amount of drug in central compartment
p, is the known amount of drug in peripheral
compartment T.
 Hence total amount of drug in body can be
calculated by;
T/p= k12 (k21-β)
Where β=slow disposition rate constant
T/p=estimates the relative
distribution of drug B/w
compartments
Vss=estimate extent of distribution in
body

15.  Metabolism is the conversion of a drug to
another chemical form and this is considered
in the design of sustained release system for
the drugs.
 Factors associated with metabolism
1.ability of the drug to induce or inhibit
enzyme synthesis.
2.fluctuating drug blood level and first pass
metabolism
ex- nitroglycerine

16.  The rate of elimination of drug is described quantitatively
by its biological half life.
t1/2= 0.693 v/cls
Where v=volume of distribution
cls=systemic clearence
cls = I.V administered dose
AUC
where,
AUC=area under curve,sq.cm

17. Significance of Half life
 Drug having shorter half life requires frequent
dosing, making it desirable to develop SDRS.
This will be opposite for drugs with higher half lives.
 Drug with half life less than 2hrs and those with more
than 8hrs should not be used.
ex-for drugs with half life less than 2hrs
Ampicillin, furosemide, penicillin…etc
for drugs with more than 8hrs of half life
Diazepam, digitoxin,digoxin …etc

18.  Minimizing side effect for a particular drug done by
controlling its plasma concentration and using less total
drug over time course of therapy.
 To measure margin of safety of drug its therapeutic index
is considered.
TI= TD50/ED50
Where, TD50-median toxic dose
ED50-median effective dose

19. THANK YOU !