PH of time, have been used to control

Sensitive Drug Delivery System


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Controlled drug delivery systems that
are considered to deliver drugs at predetermined rates for predefined periods
of time, have been used to control the limitations of conventional drug
formulations. In some cases drug has to be delivered in response to pH in the
body, in fact it would be advantageous if the drug could be administered in a
manner that precisely matches the physiological needs at proper times at the specified
target sites. The range of fluids in various sections in the GIT may provide
environmental stimuli that are responsive to drug release ph. Stimuli-responsive
polymers are one of the most important excipients in in DDS and pharmaceutical
formulations. These are designed to produce specific and desired PH
concentration activated response according to body physiological environment

PH sensitive drug delivery systems
(PSDDS) deliver the drug at specific time as per the pathophysiological need of
the body and gives improved patient compliance and therapeutic efficacy that is
why it is gaining importance.  


All the PH sensitive polymers consist of
pendant acidic (carboxylic acid and sulfonic acids) and basic (ammonium salts)
groups that either accept or release protons in response to changes in environment
PH. The polymers having large number of ionizable groups are called

The charge density of the polymers is
dependent on the PH and ionic concentration of the outer solution (in which the
polymer is introduced). Swelling or de-swelling of the polymer can be caused by
altering the pH of the solution.

1.      At
low pH Poly-acidic polymers are un-swollen as the acidic groups will be
protonated and thus unionized.

2.      With
increasing pH poly-acidic polymers are going to swell

3.      In
polybasic polymers with decreasing pH ionization of basic group is going to

4.      Derivatives
of acrylic acid are most commonly used pH sensitive polymers.

Methodologies for PH Sensitive Drug Delivery

Properties of PH Sensitive Hydrogel

Hydrogels are made up of cross linked
polyelectrolytes that have large differences in swelling properties depending
upon the environmental PH. The pendant acidic or basic groups on
polyelectrolytes experience ionization however it is difficult due to
electrostatic effects applied by other adjacent ionized groups, making the
apparent dissociation constant (ka) different from that of corresponding
monoacid or monobase ionizable groups presence on polymer chains results in
swelling of the hydrogels. The swelling of the polyelectrolyte hydrogels
happens due to the electrostatic repulsion among charges that are present on
the polymer chain , the extent of swelling can be influenced by any condition
that lessen electrostatic repulsion such as pH, ionic strength and type of counter
ions. The swelling and pH responsiveness of polyelectrolyte hydrogels can be
balanced by using the neutral comonomers such as 2-hydroxyethyl methacrylate
and methyl methacrylate.

Different comonomers provide different
hydrophobicity to the polymer chain, as a result different pH sensitive
behaviour is shown.


Hydrogels made up of poly methacrylic
acid attached with poly ethylene glycol have unique PH sensitive properties. The
acidic protons of carboxylic acid of PMA at low PH interact with ether oxygen
of PEG through hydrogen bonding resulting in condensation of hydrogels. At high
PH the carboxylic groups of PMA become ionized, the resulting complexation
results in swelling of the hydrogels.

Applications of pH sensitive hydrogels

Controlled drug delivery

PH Sensitive hydrogels are usually used
to develop controlled release formulations for oral administration. The pH in
stomach (