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Bioavailability is defined as the rate and extent/amount

. of absorption of unchanged drug from its dosage form


It is one of the important parameter to achieve desired
concentration of drug in systemic circulation for
.pharmacological response to be shown
A Drug with poor bioavailability is one with poor
aqueous solubility, slow dissolution rate in biological fluids,
poor stability of dissolved drug at physiological pH, poor
permeation through biomembrane and extensive
.presystemic metabolism
Poorly water soluble drugs often require high doses in
order to reach therapeutic plasma concentrations after
.oral administration
Low aqueous solubility is the major problem encountered
.with formulation development of new chemical entities
Any drug to be absorbed must be present in the form of
.an aqueous solution at the site of absorption
With the advancement of technology, different
techniques are used for the enhancement of bioavailability
of drugs including particle size reduction, solubilising
excipients, colloidal drug delivery systems, pH
adjustment, co-solvency, micellar solubilisation,
hydrotropy , solid dispersion, complexation, and so
.forth
There are 3 major approaches to overcome the
: bioavailability problems
:A) pharmaceutics approach
Modification of formulation, manufacturing processes or
.physicochemical properties of the drug is done
:B) pharmacokinetic approach

Pharmacokinetics of drug is altered by modifying its


.chemical structure

:C) biological approach


In this, route of drug administration may be changed such
as parenteral form instead of oral form. Rate dissolution
and its solubility are very important factors in third
.approach
The second approach of chemical modification has
number of drawbacks such as being very expensive,
time consuming, requires repetition of chemical studies,
..risk of precipitation and adverse effects
The attempts, whether optimizing the formulation,
manufacturing processes or physicochemical properties of
the drug, are mainly aimed at enhancement of
dissolution rate as it is the major rate limiting step
.in the absorption of most drugs

Co- solvency
The solubility of a poorly water soluble drug can be
increased frequently by the addition of a water miscible
solvent in which the drug has good solubility known as
.cosolvents
Co- solvents are mixtures of water and one or more
water miscible solvents used to create a solution with
.enhanced solubility for poorly soluble compounds
This is one of the most widely used techniques because it
.is simple to produce and evaluate

Example of solvents used in co-solvent mixtures are PEG


.300, propylene glycol or ethanol
Co-solvent formulations of poorly soluble drugs can be
.administered orally and parenterally
:Advantages
.Simple and rapid to formulate and produce
:Disadvantages
As with all excipients, the toxicity and tolerability related
with the level of solvent administered has to be
.considered
Uncontrolled precipitation occurs upon dilution with
.aqueous media

Particle size reduction


The bioavailability intrinsically related to drug particle
.size
By reducing particle size, increased surface area
.improves the dissolution properties
Particle size reduction, it is done by milling techniques
.using for example jet mill
Not suitable for drugs having a high dose number
because it does not change the saturation solubility of the
.drug
Nowadays particle size reduction can be achieved by
.micronisation and nanosuspension
:Advantages
-.Typically, low excipient to drug ratios is required
-. Formulations are generally well tolerated
:Disadvantages

Due to the high surface charge on discrete small particles, there is a strong tendency for particle
.agglomeration

Solid dispersions
The effective surface area is one of the important factors
.governing the dissolution rate of poorly soluble drugs
In addition to the micronization and nonosizing
technologies, solid dispersions is the other way of
enhancing the effective surface area available for
.dissolution
Solid dispersion involve the dispersion of one or more
active ingredients in an inert carrier or matrix at solid
.state
These are usually prepared by heating mixtures of the
drug and carrier to a molten state, followed by
.resolidification by way of cooling
This melt method often requires relatively high
temperatures (>100 C), which may lead to thermal
.degradation of the drug
Solvent evaporation method is another technique of
preparing solid dispersions which involves dissolving the
components in a mutual volatile solvent followed by
evaporation (spironolactone, itraconazole and
.prednisolone)
The solvent evaporaton method has several
:disadvantages
It is time consuming and expensive because of long
.processing and drying times
Moreover, it is not environment-friendly due to the use
of organic solvents, and may have toxic residual solvent(s)
.in the final product

Another interesting approach of producing solid


dispersion without the use of organic solvents is the use of
.melt extrusion technology
In this process, heat is used to make thermoplastic
materials pliable enough to incorporate drug particles in
.the polymer matrix
The decomposition of drug and/or carrier is unlikely with
melt extrusion technology as the processing temperature
is lower than the melting point of the drug and the
.softening temperature of the polymer (carrier)

The bioavailability of the drug is the most


important factor that controls the formulation of
the drug as well as therapeutic efficacy of the drug,
hence the most critical factor in the formulation
.development
Dissolution of the drug is the rate determining
step for oral absorption of the poorly water soluble
drugs and solubility is also the basic requirement
for the formulation and development of different
.dosage form of different drugs
The various techniques described above alone or
in combination can be used to enhance the
.bioavailability of the drug