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 variations.
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
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 polyelectrolytes
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.
low pH Poly-acidic polymers are un-swollen as the acidic groups will be
protonated and thus unionized.
increasing pH poly-acidic polymers are going to swell
polybasic polymers with decreasing pH ionization of basic group is going to
of acrylic acid are most commonly used pH sensitive polymers.
Methodologies for PH Sensitive Drug Delivery
Properties of PH Sensitive Hydrogel
Hydrogels comprises 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
exerted 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