1, AQUEOUS SOLUBILITY
It is 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.
Dissolution rate is related to aqueous solubility which is given by NOYES-WHITNEYS
2, PARTITION COEFFICIENT
between the time that a drug is administered and the time it is eliminated from the
It diffuse through a variety of biological membranes that act primarily as lipid like
The major criteria in evolution of the ability of a drug to penetrate these lipid
membranes is it apparent oil-water partition coefficient defined as :-
3, DRUG STABILITY
In oral dosage form, loss of drug through acid hydrolysis or metabolism in GIT.
A drug in solid state undergoes degradation at much slower rate than drug in
Drugs with low aqueous solubility have low dissolution rate and usually suffer oral
Aqueous solubility of weak acids and base is governed by pka value and PH of the
4, PROTEIN BINDING
Distribution of 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.
Some drug shows higher degree protein binding ex-Diazepam shows greater than 95%
5, MOLECULAR SIZE AND DIFFUSIVITY
Ability of drug to diffuse through membrane is called as diffusivity, is a function of
In most of polymers, its possible to logD empirically to some function of molecular
LogD=Sv log V+Kv=-Sm log M+Km
Rate, extent and uniformity of absorption are the important factors when considering
Since the 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
The distribution of drug in to vascular and extra vascular 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.
Volume of distribution obeys only one compartment model
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
4, ELIMINATION AND BIOLOGICAL HALF LIFE
The rate of elimination of drug Is described quantitatively by its biological half life.
t½= 0.693 v/cls
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.
5, SIDE EFFECTS AND SAFETY CONSIDERATION
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.
• Book of dosage form design consideration written by Rakesh K. Tekade in
• Book of design of controlled released drug delivery system written by
Bhaskara R. JASTI