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American Journal of Advanced Drug Delivery
ug Delivery
Am
ISSN: 2321-547X
http://www.imedpub.com/advanced-drug-delivery/
Review Article
The term “Drug Delivery” covers a very extensive Approaches to overcome these limitations:
range of techniques used to deliver therapeutic agents • Development of new, better and safer drugs
into the human body. Drugs are administered with a with long half-life and large therapeutic indices.
main aim of curing patient ailments. Drugs are never • Effective and safer use of existing drugs
administered in their pure form but are converted in through concepts and techniques of controlled and
a suitable formulation so that its onset and intensity targeted drug delivery systems4, 5.
of action as well as total duration of action can be
The first approach has many disadvantages,
checked. Among the various routes of drug delivery
however second approach can be used widely.
oral route is most widely used route of drug delivery.
But conventional dosage form offers few limitations An ideal controlled drug delivery system is that
which could be resolved by modifying the existing which delivers the drug at a specific rate locally
dosage form1,2. or systemically for a specified period of time with
minimum fluctuation in plasma drug concentration,
Limitations of conventional oral dosage form: reduced toxicity and maximum efficiency6.
• Poor patient compliance; chances of dose For successful development of drug delivery
missing. system basic understanding of several aspects is
• See-saw fluctuations. necessary:
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Coating dissolution system: In this type are based on the principle of osmosis. Such
of system the drug particles are coated with systems release the drugs at a constant zero
polymers like cellulose, polymethacrylates, order rate. These systems are popularly known
PEGs etc. The resulting pellets are compressed as as OROS.
tablets. The dissolution rate of the coat depends The system consist of a drug core and an
upon thickness and solubility of coat40 (Figure osmotically active substance (osmogen) like
4). mannitol surrounded by a semipermeable
membrane coating with an orifice of 0.4 mm
Soluble matrix system: These systems are also made by laser beam to facilitate drug exit.
known as monoliths as the drug is homogenously When exposed to GI Fluids, water flows though
dispersed in a rate controlling medium. Waxes semipermeable membrane, under the influence
like bee wax, carnauba wax etc. are used for of osmotic force of osmogen the drug release is
controlling the dissolution rate. facilitated via orifice.
The rate of dissolution is controlled by either These systems could be of two types:
of following mechanisms: In type-A system drug splution along with
• Altering the rate of fluid penetration into osmogen is surrounded by a semi permeable
tablet by altering the porosity of tablet. membrane.
• Decreasing the wettability of tablet. In type-B system, the drug solution is present
in a semi permeable membrane surrounded by
• Slow dissolution rate of polymer6,7
the electrolytes (Figure 6).
(Figure 5).
pH independent formulations: These systems
Ion exchange resins: Based upon the principle are designed for acid-labile drugs or drugs
that GIT has a relatively constant level of ions, irritating GIT mucosa and targeting their delivery
this type of system has developed for controlling to the intestinal tract. It is fabricated by coating
the rate of delivery of ionisable or ionic drugs. the core of tablet with a combination of intestinal
Such a system can be prepared by incubating fluid insoluble polymer (ethyl cellulose) and
the drug resin solution or by passing the drug intestinal fluid soluble polymer (HPMCP).
solution through a column containing exchange The coating membrane resists the dissolution
resin. A cationic drug is complexed with a resin of drug in stomach at acidic pH. After gastric
containing SO3- group and for anionic drug resin emptying the system travels to small intestine.
containing N(CH3)3 group is used. In the GIT At a pH above 5 the intestine soluble component
dissolves; thereby producing a porous membrane
hydronium and chloride ions diffuses into the
that controls the release of drug from the core of
sustained release tablet and interact with drug- the tablet.
resin compex to trigger the release of drug.
Altered density formulations: The transit time
+Types of ion exchange resins: of GI contents is usually less than 24 hours. This
Cationic exchange resin: Contains acidic is major limiting factor in design of sustained
functional group. release formulation. If the residence time of
drug in stomach or intestine is prolonged the
Anion exchange resin: Contains basic frequency of dosing can further be reduced. This
functional group. could be achieved by altering the density of drug
particles, using mucoadhesive polymers or by
These systems prevent dose dumping as
altering the size of dosage form.
they have better drug retaining properties. So,
chances of toxicity are reduced. Moreover, the Altered density formulation can further be
polymeric and ionic property of ion exchange classified as:
resin makes the drug release more uniform than i) High density approach
that of simple matrices41.
The density of GI fluids is about 1.4 g/
Method using osmotic pump: Osmotic systems cc so the drug particles having density greater
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than this value usually 1.6 g/cc can be used for Disadvantages of matrix tablets:
this purpose. These systems have prolonged • Matrix needs to be removed after drug
residence time and not affected by presence of release.
food. Iron oxide and barium sulfate can be used
for this purpose. • Costly in comparison to conventional
dosage form.
ii) Low density approach
• Presence of food and gut transition time can
These pellets have density lower than that affect the release rate10.
of GI fluids. So, such tablets tend to float on
gastric juice for an extended time period thereby Classification of Matrix Tablets
slowing down the drug release. Such system can A) On the basis of retardant material used
be formulated by granulating a drug with 20- matrix can be divided into 5 types:
80% of hydrogel like HPMC, HPC and HEC. On
Hydrophobic matrices (plastic matrices):
contact with GI fluids, tablets swells and form a
diffusible gel barrier that lowers the density of In this technique hydrophobic inert polymer
the system lower than 1; thereby allowing it to are used as release retarding matrix material.
float. The drug is mixed with the hydrophobic inert
polymer (e.g. polyethylene, poly vinyl chloride,
Matrix Tablet
ethyl cellulose) and then compressed into tablet.
Matrix tablet is defined as “Oral solid dosage The drug is entrapped between the network
form in which active pharmaceutical ingredient channels of polymer particles thereby sustaining
is uniformly dispersed throughout polymeric the release of drug.
matrices (hydrophilic or hydrophobic) which
Lipid matrices:
retards the drug release rate.
Lipid material is used as release retardant
This approach is widely used for formulating
(e.g. carnauba wax in combination with stearyl
the sustained release tablets. The mechanism
alcohol). Mechanism involved in drug release
involved in the drug release is either dissolution
includes both pore diffusion and matrix erosion.
controlled or diffusion controlled.
Hydrophilic matrices:
Advantages of matrix system:
• Easy to manufacture. In this type of system a variety of hydrophilic
polymers can be used, such systems are also
• Cost effective. known as swellable matrices. These polymers
• Improved patient compliance. are more preferred than former ones as they are
cost effective and a desirable drug profile can be
• Sustained release formulations avoid the
easily obtained.
high blood concentration.
Classification of hydrophilic polymer
• Reduce drug toxicity by slowing down drug
matrices:
absorption.
• Enhanced drug stability in GI milieu. • Cellulose derivatives: Methyl cellulose
400 and 4000cPs; Hydroxy ethyl cellulose,
• Minimize the local and systemic side effects. Hydroxy propyl methyl cellulose (HPMC)
• No see-saw fluctuations in plasma drug 25, 100, 4000 and 15000cPs and Sodium
concentration profile. carboxy methyl cellulose.
• Less amount of drug is required. • Non cellulose natural and semi-synthetic
polymers: Agar-Agar; alginates; carob gum;
• Temporal effects can be provided. e.g.
morning relief of arthritis through bed time molasses; polysaccharides of galactose and
dosing. mannose; chitosan and modified starches.
• Polymer of acrylic acid: carbopol-934.
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Figure 1. Plasma drug concentration vs. time profile for oral conventional dosing and single oral
dose of sustained and controlled release formulation
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Figure 7. Schematic representation of drug release from different type of matrix tablet
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