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SEMINAR
ON
SUSTAINED RELEASE
DRUG DELIVERY
SYSTEM
HIGH HIGH
LOW LOW
INTRODUCTION
However, an ideal dosage regimen would be one, in which the
concentration of the drug, nearly coinciding with minimum
effective concentration (M.E.C.), is maintained at a constant level
throughout the treatment period. Such a situation can be graphically
represented by the following figure
CONSTANT LEVEL
INTRODUCTION
The basic goal of therapy is to achieve steady state blood level that
is therapeutically effective and non toxic for an extended period of
time.
Where
Ke = overall elimination (first order kinetics).
Vd = total volume of distribution.
Cd = desired drug concentration.
B) Dose consideration :-
To achieve the therapeutic level & sustain for a given period of time
for the dosage form generally consist of 2 part
W = Di + Dm
W= Di + K0 r. Td
W = Di + K0 r Td K0 r Tp
W = Di + ( Ke Cd /Kr ) Vd
Sustained release, sustained action, prolonged action,
controlled release, extended action, time release dosage formed are
terms used to identify drug delivery system that are designed to
achieve a prolonged therapeutic effect by continuously releasing
medication over an extended period of time after administration of
single dose .
Developing the new better and safer drug with long half life &
large therapeutic indices.
Drug with slow rate of absorption and elimination i.e. short half life
less then 2 hr are difficult to formulate as system requires a larger
unit dose size and may contribute to patient complains problem and
also difficult to control the release rate of drug.
Drug should be uniformly absorbed throughout GI tract.
Drug that are absorbed poorly and at unpredictable rate are not good
candidate for SRDF because there release rate and absorption are
depending on the position of drug in the GI tract and rate movement
of drug.
e.g.- Riboflovin is not absorbed in GI tract.
The drug should not show any cumulative action, any undesired
side effect as in case of dose dumping it might produce toxicity.
Some drug does not have any clear advantage for SRDF like
Cqiseuilin.
Drug properties relevant to sustained release
formulation
1. Physicochemical properties
2. Biological properties
Factors to be considered In S.R.Dosage forms.
Since it not only lowers the concentration of drug but it also can
be rate limiting in its equilibrium with blood and extra vascular
tissue, consequently apparent volume of distribution assumes
different values depending on time course of drug disposition.
Vd = dose/C0
Where:
Where:
V1= volume of central compartment
K12= rate constant for distribution of drug from central to
peripheral
K21= rate constant for distribution of drug from peripheral to
central
Vss= estimation of extent of distribution in the body
Vss results concentration in the blood or plasma at steady state
to the total mount of the drug present in the body during respective
dosing or constant rate of infusion. Equation 2 is limited to those
instance where steady state drug concentration in both the
compartment has been reached. At any other time it tends to
overestimate or underestimate.
To avoid ambiguity inherent in the apparent volume of
distribution as an estimation of the amount of drug in the body. The
T/P ratio is used.
Where:
= TD50/ED50
Larger the TI ratio the safer is drug.
It is imperative that the drug release pattern is precise so that the
plasma drug concentration achieved in under therapeutic range.
2. Physiological Factors:
a) Dosage size.
c) Aqueous Solubility.
d)Drug stability.
e) Protein binding.
f) Pka
1.Dosage size.
When the drug is administered to the GIT ,it must cross a variety
of biological membranes to produce therapeutic effects in another
area of the body.
It is common to consider that these membranes are lipidic,
therefore the Partition coefficient of oil soluble drugs becomes
important in determining the effectiveness of membranes barrier
penetration.
However for some drugs which are unstable in small intestine are
under go extensive Gut Wall metabolism have decreased the bio
availability .
When these drugs are administered from a sustained dosage form
to achieve better bio availability, at different routes of the drugs
administered should be chosen
Eg. Nitroglycerine
The presence of metabolizing enzymes at the site or pathway can
be utilized.
5.Protein binding.
It is well known that many drugs bind to plasma protein with the
influence on duration of action.
The pka range for acidic drug whose ionization is PH sensitive and
around 3.0- 7.5 and pka range for basic drug whose ionization is ph
sensitive around 7.0- 11.0 are ideal for the optimum positive
absorption
Classification of polymers
Principle:
Drug granulated with an inert, insoluble matrix such as
polyethylene, polyvinyl acetate, polystyrene, polyamide or
polymethacrylate.
Granulation is compressed results in MATRIX
Drug is slowly released from the inert plastic matrix by leaching
of body fluids
Release of drug is by diffusion.
Methods of preparation
Solidify Granulate
Grind
Powder
Suspension of
drug in wax
Granulate
Drug
Tablets
3) Coating the drug or a dosage form containing the
drug (microencapsulation)
The method for retarding drug release
from the dosage form is to coat its
surface with a material(polymers) that
retards penetration by the dispersion
fluid. Drug release depends upon the
physiochemical nature of coating
material.
Microencapsulation is rapidly
expanding technique as a process; it is a
means of applying relatively thin coating
to small particles of solid or droplets of
liquids and dispersion.
The application of microencapsulation might will include,
sustained release or prolonged action medication, taste masked,
chewable tablet, powder and suspension, single layer tablets.
Containing chemically incompatible ingredient & new formulation
concepts for creams, ointments, aerosols, dressing, plasters,
suppositories & injectables.
H 2O
- -
- SO3- NH3+ - A + NaCl - -SO3 Na+ + A-NH3+ Cl
Basic pH un dissociated
The particle size governs the dissolution rate and hence the
bioavailability of drug. Consequently this parameter may be
exploited to prolong its action. This principle is used in the
formulation of the hypodermic tablets which retain their size over
long period of time releasing the drug slowly.
Liquid products:
It is possible to formulate liquid product, having sustained action,
by suspending coated granules or particles in a suitable liquid media
which has no action on the coats of the granules. These formulation
are similar to suspensions.
Evaluation
Specified in monograph.
Rotating bottle
Sartorius device
Advantages: