Novel GIT drug delivery
Oral Osmotic DDS
Ion exchange controlled DDS
pH controlled DDS
1. Oral Osmotic DDS:
Oral drug delivery is
the most favored and suitable option as the oral route provides all out active
surface area from other drug delivery system for administration of several drugs.
In conventional oral drug delivery systems, there are no such parameters to
have such accessible control over release of the drug and effective
concentration at the diseased site. It was achieved by uneven administration of
number of doses.
This type of dosing
pattern result is variation in therapeutic plasma concentrations, that results
in serous side-effects .Furthermore, the degree and magnitude of absorption of
drug from conventional dosage forms may differs depending on reasons such as addition
of excipients, physicochemical aspects of the drug, several physiological
factors such as presence or absence of food, pH of gastro intestinal tract, gastro
intestinal motility and so on. Abrupt release of drug without having control may
lead to local gastro intestinal or systemic toxicity. Therefore, various tactics
are made in designing the formulations, which will overwhelm the shortcomings of
conventional dosage forms, which comprises sustained/controlled drug delivery
system. There are three main classes of controlled-release drug delivery
system; transdermal, intravenous, and oral systems
Alza Corporation R of
USA was the first to develop an oral osmotic pump.
Osmotic drug delivery system for oral and
parenteral use offer diverse and applied benefits over other means of delivery.
The following advantages provided to the acceptance of osmotic drug delivery
provide a zero order release profile after an initial lag.
may be delayed or pulsed if preferred.
release is free of gastric pH and hydrodynamic condition.
are well categorized and understandable.
release mechanisms don’t rely on drug.
high grade of in-vitro and in-vivo correlation (ivivc) is achieved in
logical for this approach is that the presence of water in GIT is persistent,
in terms of the volume required for activation and controlling osmotically base
release rates are achievable with osmotic systems compared with previously diffusion-controlled
drug delivery systems.
release from osmotic systems is slightly affected by the presence of food in
release rate of osmotic systems is precisely attained and can be automated by modifying
the release control parameters.
the coating process is not controlled there is a threat of film defects, which marks
in dose dumping
hole is important
of Dose wastage
therapy is not possible in the case of unpredicted adverse events.
Principle and basic concept of osmotic drug delivery system:
It is founded on the principle of osmotic
pressure. Osmotic pressure is a colligative property, which rely on
concentration of solute that is important factor of this phenomenon. Solutions
of varying concentrations having the same solvent and solute system illustrates
that osmotic pressure is proportionate to their concentrations. Thus a continuous
osmotic pressure, and thereby a constant influx of water can be obtained by an
osmotic drug delivery system.
Osmotic pressure is proportional to temperature and concentration and
the association can be explained by following equation.
? = n2 RT
Where, ? = osmotic coefficient
n2 = molar concentration of solute in the
R = gas constant
T = Absolute temperature
Basic formulation concept:
Osmotic drug delivery devices comprises of an
osmotically active drug core, which
is bounded by a rate controlling semipermeable membrane. Osmotic drug delivery system
varies from diffusion based systems in that the method of delivery of the active agents is compelled by an osmotic gradient
somewhat than the concentration of drug in the device. In the convenient
and easy type of osmosis-controlled drug release the following order of steps
are included in the release process:
1. Osmotic transport of fluid
into release unit.
2. Dissolution of drug into the
3. Transport of a saturated
drug solution by driving of the solution through a single hole via pores in the
semi permeable membrane4.
4. The transport of active
agent from oral osmotic systems is maintained by the
5. Influx of solvent via semi-permeable
membrane, which in turn delivers the active agent to the external environment.
Basic component of osmotic DDS
§ Drug : functioned
as a osmogen else osmogenic salt is added in formulation’
§ Semi-permeable membrane :
Adequately wet strength and water permeability.
Should be biocompatible and inflexible.
Should be adequately thick to withstand the
pressure of device.
Any polymer that is absorbent to water but impermeable
to solute can be used as a coating substance .e.g.; Cellulose acetate,
cellulose triacetate and ethyl cellulose.
§ Hydrophilic and hydrophilic
polymers : CMC,
HPMC , HEC
§ Wicking agent : SLS ,
PYP , Bentonite
§ Solubilizing agent : PVP
,CP , PEG
§ Osmogens : Nacl , KCl
§ Plasticizer : Phathaltes , benzoates , TEC
§ Flux regulator : Polypropylene , polybutylene
§ Pore forming agent : Calcium nitrate , Potassium sulphate
§ Coating solvent : acetone and methanol (80:20) , acetone and water
§ Surfactants : poly oxyethylenated castor oil
that affect the drug release from osmotic delivery of drugs:
The drug releases
from osmotic delivery device rely on various process and formulation factors.
Apart from the water solubility of the drug, the solubility of the other fundamental
ingredients can also have a major impact on the drug release by creating an
osmotic pressure gradient across the polymeric coating on interaction with
dissolution medium. The extents of drug release from osmotic pumps rely on the
total solubility and the osmotic pressure of the drug. Many factors that influence
the release of drug from osmotic system are follows:
Osmotic delivery systems comprises of at least one delivery orifice in
the semipermeable membrane for drug release and the size of delivery hole
should be optimized in order to regulate the drug release from osmotic
systems . To obtain an optimum zero-order delivery profile, the cross
sectional area of the hole should be
smaller than a size Smax to minimum drug delivery
by diffusion through orifice. Moreover, the area must be sufficiently large,
above a minimum size Smin, to lessen the
hydrostatic pressure developed in the device. Else, the hydrostatic pressure
can break the membrane and influences the zero-order delivery rate of drug.
Therefore, the cross sectional area of the orifice must be maintained between
minimum and maximum values.
The release rates of drug rely on the solubility of the solute inside
the drug delivery device. Subsequently, drugs should have adequate solubility
to be delivered by osmotic delivery on the other hand, most water-soluble drugs
would revealed high release rate that would be zero-order for a small
percentage of the initial drug load. In the case of low solubility compounds, various
other approaches may be applied and can be divided into two categories. First,
swell- able polymers can be added that gives in the delivery of poorly soluble
drugs in the form of a suspension. Second, the drug solubility can be altered
by using different techniques.
Semi permeable Membrane:
The choice of a
rate-controlling membrane is an significant characteristic in the formulation design
of osmotic systems. Drug release from osmotic systems is not affected by pH and
agitational force of the gastrointestinal tract to a large degree because of
the reason that selectively water permeable membrane and operative isolation of
dissolution from the gut environment. The thickness of membrane is kept between
200 and 300 mm
A capsule device coated with
uneven membranes to transport drugs having poor water-solubility (Fig. 1). In the examples, solubility of a poorly
water-soluble drug such as glipizide was increased by using bicarbonate, it was
used as encapsulated excipients (pH-controlling excipients) inside the capsule
device. The solubility modifier (meglumine), in the form of mini-tablets, was layered
with a rate controlling membrane to delay its availability within the core.
Thus, the solubility of glipizide was enhanced to its delayed release from the