A NOVEL DRUG DELIVERY SYSTEM

INTRODUCTION
The method by which a drug is delivered can have a significant effect on its efficacy. Some
drugs have an optimum concentration range within which maximum benefit is derived, and
concentrations above or below this range can be toxic or produce no therapeutic benefit at all on
the other hand, the very slow progress in the efficacy of the treatment of severe diseases, has
suggested a growing need for a multidisciplinary approach to the delivery of therapeutics to
targets in tissues.
From this, new ideas on controlling the pharmacokinetics, pharmacodynamics, non-specific
toxicity, immunogenicity, biorecognition, and efficacy of drugs were generated. These new
strategies, often called drug delivery systems (DDS), which are based on interdisciplinary
approaches that combine polymer science, pharmaceutics, bioconjugate chemistry, and
molecular biology. To minimize drug degradation and loss, to prevent harmful side-effects and
to increase drug bioavailability and the fraction of the drug accumulated in the required zone,
various drug delivery and drug targeting systems are currently under development . Controlled
and Novel Drug Delivery which was only a dream or at best a possibility is now a reality. During
the last decade and half pharmaceutical and other scientists have carried out extensive and
intensive investigations in this field of drug research.
Among drug carriers one can name soluble polymers, micro particles made of insoluble or
biodegradable, natural and synthetic polymers, microcapsules, cells, cell ghosts, lipoproteins,
liposomes, and micelles. The carriers can be made slowly degradable, stimuli-reactive (e.g., pH-
or temperature-sensitive), and even targeted (e.g., by conjugating them with specific antibodies
against certain characteristic components of the area of interest). Targeting is the ability to direct
the drug-loaded system to the site of interest. Two major mechanisms can be distinguished
for addressing the desired sites for drug release are:-

(i) Passive
(ii) Active targeting

An example of passive targeting is the preferential accumulation of chemotherapeutic agents in

solid tumors as a result of the enhanced vascular permeability of tumor tissues compared with
healthy tissue. A strategy that could allow active targeting involves the surface functionalization
 A NOVEL DRUG DELIVERY SYSTEM

of drug carriers with ligands that are selectively recognized by receptors on the surface of the
cells of interest. Since ligand—receptor interactions can be highly selective, this could allow a
more precise targeting of the site of interest (see fig. 1)

FIGURE 1: TYPES OF DRUG DELIVERY

Any drug delivery system may be defined as a system comprising of:

a) Drug formulation.

b) Medical device or dosage form / technology to carry the drug inside the body.

c) Mechanism for the release.

Conventional drug delivery involves the formulation of the drug into a suitable form, such as a
compressed tablet for oral administration or a solution for intravenous administration. These
dosage forms have been found to have serious .limitations in terms of higher dosage required,
 A NOVEL DRUG DELIVERY SYSTEM

lower effectiveness, toxicity and adverse side effects. New drug delivery systems have been
developed or are being developed to overcome the limitation of the conventional drug delivery
systems to meet the need of the healthcare profession.
These systems can be characterized as controlled drug release systems and targeted drug delivery
systems.
The therapeutic benefits of these new systems include:
•Increased efficacy of the drug
•Site specific delivery
•Decreased toxicity/side effects
•Increased convenience
•Viable treatments for previously incurable diseases
•Potential for prophylactic applications
•Better patient compliance
There is no uniform and established definition of drug delivery systems. It is assumed to be
based on two basic parameters:
Route of entry (A).
Dosage form (B).
Any member of the cartesian product of (A X B) is defined as a drug delivery system. Such a
definition implies that there are a vast number of members in this group. Many of them may not
even be feasible, while many others may not be relevant. So, the set of most relevant new drug
delivery systems is deduced as follows:
 A NOVEL DRUG DELIVERY SYSTEM

Various Drug Delivery Systems:

1. Carrier based Drug Delivery System:

A) Liposomes

B) Nanoparticles

C) Microspheres

D) Monoclonal antibodies

E) Neosomes

F) Resealed erythrocytes as drug carriers

2. Transdermal Drug Delivery Systems:

A) Sonophoresis

 Mucoadhesive delivery systems

 Supramolecular delivery systems

 Variable release delivery systems

B) Osmotic pump

C) Microencapsulation

CARRIER BASED DRUG DELIVERY SYSTEM: Colloidal drug carrier systems such as
micellar solutions, vesicle and liquid crystal dispersions, as well as nanoparticle dispersions
consisting of small particles of 10—400 nm diameter show great promise as drug delivery
systems. When developing these formulations, the goal is to obtain systems with optimized drug
loading and release properties, long shelf-life and low toxicity . The incorporated drug
participates in the microstructure of the system, and may even influence it due to molecular
interactions, especially if the drug possesses amphiphilic and/or mesogenic properties
 A NOVEL DRUG DELIVERY SYSTEM

FIGURE 2: DIFFERENT PHARMACEUTICAL CARRIERS

Pharmaceutical Carriers: Micelles formed by self-assembly of amphiphilic block copolymers

(5-50 nm) in aqueous solutions are of great interest for drug delivery applications. The drugs can
be physically entrapped in the core of block copolymer micelles and transported at oncentrations
that can exceed their intrinsic water- solubility. Moreover, the hydrophilic blocks can form
hydrogen bonds with the aqueous surroundings and form a tight shell around the micellar core.
As a result, the contents of the hydrophobic core are effectively protected against hydrolysis and
enzymatic degradation. In addition, the corona may prevent recognition by the eticuloendothelial
system and therefore preliminary elimination of the micelles from the bloodstream)
A final feature that makes amphiphilic block copolymers attractive for drug delivery applications
is the fact that their chemical composition, total molecular weight and block length ratios can be
easily changed, which allows control of the size and morphology of the micelles.
Functionalization of block copolymers with crosslinkable groups can increase the stability of the
corresponding micelles and improve their temporal control. Substitution of block copolymer
 A NOVEL DRUG DELIVERY SYSTEM

micelles with specific ligands is a very promising strategy to a broader range of sites of activity
with a much higher selectivity
Liposomes: Liposomes are a form of vesicles that consist either of many, few or just one
phospholipid bilayers. The poiar character of the liposomal core enables poiar drug molecules to
be encapsulated. Amphiphilic and lipophilic molecules are solubilized within the phospholipid
bilayer according to their affinity towards the phospholipids. Participation of nonionic
surfactants instead of phospholipids in the bilayer formation results in neosomes. Channel
proteins can be incorporated without loss of their activity within the hydrophobic domain of
vesicle membranes, acting as a size-selective filter, only allowing passive diffusion of small
solutes such as ions, nutrients and antibiotics.
Thus, drugs that are encapsulated in a nanocage-functionalized with channel proteins are
effectively protected from premature degradation by proteolytic enzymes.
The drug molecule, however, is able to diffuse through the channel, driven by the concentration
difference between the interior and the exterior of the nanocage
 A NOVEL DRUG DELIVERY SYSTEM

STRUCTURE OF LIPOSOME

FIGURE 3: STRUCTURE OF LIPOSOME

Dendrimers are nanometer-sized, highly branched d monodisp erse macromolecules with

symmetrical architecture. They consist of a central core, branching units and tenninal functional
groups. The core together with the internal units, determine the environment of the nanocavities
and consequently their solubilizing properties, whereas the external groups the solubility and
chemical behaviour of these polymers. Targeting effectiveness is affected by attaching targeting
ligands at the external surface of dendrirners, while their stability and protection from the
Mononuclear Phagocyte System (MPS) is being achieved by functionalizatiotiof the dendrimers
with polyethylene glycol chains (PEG). Liquid Crystals combine the properties of both liquid
and solid states. They can be made to form different geometries, with alternative polar and non
polar layers (i.e., a lamellar phase) where aqueous drug solutions can be included.

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Nanoparticles: Nanoparticles (including nanospheres and nanocapsules of size 1 O-200nm) are

in the solid state and are either amorphous or crystalline. They are able to adsorb and/or
encapsulate a drug, thus protecting it against chemical and enzymatic degradation. In recent
years, biodegradable polymeric nanoparticles have attracted considerable attention as potential
drug delivery devices in view of their applications in the controlled release of drugs, in targeting
particular organ/or tissue, as carriers of DNA in gene therapy, and in their abilities to deliver
proteins peptides and genes through peroral route 13

Classification of nanomaterials:

A) Nanotubes- They are hollow cylinders made of carbon atoms. They can also be filled and
sealed, forming test tubes or potential drug delivery devices.

B) Nanowires- Glowing silica nanowire is wrapped around a single stand of human hair. It looks
delicate. It is about five times smaller than virus applications for nanowires include the early
sensing of breast and ovarian malignancies.

C) Nanocanifiever- The honey comb mesh behind this tiny carbon cantilever is surface of fly’s
eye. Cantilevers are beams anchored at only one end. In nano world they function as sensors
ideal for detecting the presence of extremely small molecules in biological fluid.

D) Nanoshells- Nanoshells are hollow silica spheres covered with gold. Scientists can attach
antibodies to their surfaces enabling the shells to target certain shells such as cancer cells. Nano
shells one day also are filled with drug containing polymers.

E) Quantum dots- Quantum dots are miniscule semiconductor particles that can serve as sign
pots of certain type of cells or molecules in the body. They can do this because. they emit
different wavelengths of radiations depending upon the type of cadmium used in their cores.
Cadmium sulphide for ultraviolet to blue, cadmium selinide for most of the visible spectrum and
cadmium telluride for far infrared and near infrared14.

F) Nano pores- Nano pores have cancer research and treatment applicationš. Engineered into
particles, they are holes that are so tiny that DNA molecules can pass through them one strand at
a time allowing for highly precise and efficient DNA sequencing. By engineering nanopores into

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 A NOVEL DRUG DELIVERY SYSTEM

surface of drug capsule that are only slightly larger than medicines molecular structure, drug
manufacturers can also use nanopores to control rate of drug’s diffusion in body.

G) Gold nanoparticles- These nanoparticles seen in transmission electron micrograph image,

they have solid core. Researches at north western university are using gold particles to develop
ultra- sensitive detection systems for DNA and protein markers associated with many forms of
cancer including breast, prostate cancer.

H) Bucky balls- Bucky ball is common for a molecule called buckminsterfullerene, which is
made of 60 carbon atoms formed in shape of hollow ball discovered in 1985. Bucky balls and
other ftillerenes because of their chemistry and their unusual hollow cage like shape extremely

stable and can withstand high temperatures.

APPLICATIONS- Bucky balls may see widespread use in future products and applications,
from drug delivery vehicles for cancer therapy to ultrahard coating and military harmor. Bucky
ball- Antibody combination delivers anttumor drugs.

•Bucky balls to fight allergy.

•Bucky balls as powerful antioxidants and also inhibitor of HIV.

DEMERITS:

•Bucky balls hurt cells.

•Bucky balls have high potential to accumulate in living tissue.
•Difficulty of targeting drug delivery location.
Carbon nanotubes: Carbon nanotubes can be modified to circulate well within thebody. Such
modifications can be accomplished with covalent or non covalent bonding. Modifications can
increase or decrease circulation time within the body. Carbon nanotubes no significant toxicity
when they have modified so as to be soluble in aqueous body type fluids They enter readily into
the cells14.

Cancer cells in tumor are larger than normal cells and also exhibit leakage.• Large molecules
which circulate slowly can leak into and accumulate in cancer cell. Carbon nanotubes carrying

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active agents have been demonstrated in animal studies to do this. Researches have also used
carbon tubes to deliver the precursors of active drug which they call a prodrug. eg: Cisplatin22.

Microspheres: Microspheres are characteristically free flowing powders consisting of proteins

or synthetic polymers which are biodegradable in nature and ideally having a particle size less
than 200um. Materials used for preparing Microspheres are polymers. They are classified into
two types:

1.Synthetic Polymers

2.Natural polymers

Synthetic polymers: Poly alkyl cyanoacrylates is a potential drug carrier for parenteral as well
as other ophthalmic, oral preparations: Poly lactic acid is a suitable carrier for sustained release
of narcotic antagonist, anticancer agents such as cisplatin, cyclophosphaniide, and oxorubicin24.

Sustained release preparations for antimalarial drug as well as for many other drugs have been
formulated by using of co-polymer of poly lactic acid and poly glycolic acid. Poly anhydride
microspheres (40im) have been investigated to extend the precomeal residence time for ocular
delivery.

Poly adipic anhydride is used to encapsulate timolol maleate for ocular delivery. Poly acrolein
microspheres are functional type of microspheres. They do not require any activation step since
the surfacial free CHO groups over the poly acrolein can react with NH2 group of protein to
form Schiff’ s base’5.

In case of non-biodegradable drug carriers, when administered parenterally, the canier remaining
in the body after the drug is completely released poses possibility of carrier toxicity over a long
period of time. Biodegradable carriers which degrade in the body to non-toxic degradation
products do not pose the problem of carrier toxicity and are more suited for parenteral
applications

Synthetic polymers are divided into two types.

a) Non-biodegradable polymers

b) Poly methyl methacrylate (PMMA)

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 A NOVEL DRUG DELIVERY SYSTEM

 Glycidyl methacrylate

 Epoxy polymers

b. Biodegradable polymers

 Lactides, Glycolides& their co polymers

 Poly alkyl cyano acrylates

 Poly anhydrides

Natural polymers. Natural polymers obtained from different sources like proteins, carbohydrates
and chemically modified carbohydrates.

Proteins: Albumin, Gelatin, and Collagen

Carbohydrates: Agarose, Carrageenan, Chitosan, Starch

Chemically modified carbohydrates: Polydextr4n, Poly starch.

Albumin is a widely distributed natural protein. It is considered as a potential carrier of drug or

proteins (for either their sitespecific localization or their local application into anatomical
discrete sites). It is being widely used for the targeted drug for the targeted drug delivery to the
tumour cells’6.

Gelatin microspheres can be used as efficient carrier system capable of delivering the drug or
biological response modifiers such as interferon to phagocytes. Starch belongs to carbohydrate
class. It consists of principle glucopyranose unit, which on hydrolysis yields D-glucose. It being
a poly saccharide consists of a large number of free OH groups. By means of these free OH
groups a large number of active ingredients can be incorporated within as well as active on
surface of microspheres. Chitosan is a deacylated product of chitin. The effect of chitosan has
been considered because of its charge. It is insoluble at neutral and alkaline pH values, but forms
salts with inorganic and organic salts Upon dissolution, the ammo groups of chitosan get
protonated, and the resultant polymer becomes positively charged 17

Resealed Erythrocytes as Drug Carriers: Erythrocytes, the most abundant cells in the human
body, have potential carrier capabilities for the delivery of drugs. Erythrocytes are
biocompatible, biodegradable, possess very long circulation half lives and can be loaded with a

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variety of chemically and biologically active compounds using various chemical and physical

methods 18

erythro = red and cytes = cell

Erythrocyte is red cell. Erythrocyte is biconcave discs, anucleate Filled with hemoglobin (Hb), a
protein that functions in gas transport. It contains the plasma protein spectrum.

Healthy adult male=4.5millions4tml

Healthy adult female=4.8millionl jiml

Immature RBC are called “RETICULOCYTES.”19

FIGURE 4; ERYTHROCYTES\\

Properties of resealed erythrocyte of novel drug delivery carriers:

1) The drug should be released at target site in a controlled manner.

2) It should be appropriate size, shape and should permit the passage through capillaries. And
Minimum leakage of drug should take place.

3) It should be biocompatible and should have minimum toxic effect.

4) It should possess the ability to carry a broad spectrum of drug.

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 A NOVEL DRUG DELIVERY SYSTEM

5) It should possess specific physicochemical properties by which desired target size could be
recognized.

6) The degradation product of the carriers system, after release of the drug at the selected site
should be biocompatible. It should be physico -chemically compatible with drug.

7) The carrier system should have an appreciable stability during storage.

Advantage:

1) They are natural part of body, so they are biodegradable in nature.

2) The entrapment of drug does not require the chemical modification of drugs

3) The entrapment of drug also does not require the chemical modification of the substance to be
entrapped.

4) They are non immunogenic in action and can be targeted to disease tissue/organ

5) They prolong the systemic activity of drug.

6) Isolation of erythrocyte is easy and larger amount of drug can be encapsulated in small

volume of cells

7) They can target the drug within reticuloendothelial system.

8) They facilitate incorporation of protein and nucleic acid in eukaryotic cells by cell infusion
with RBC.

Disadvantage:-

1) They have a limited potential as carrier to non-phagocyte target tissue.

2) Possibility of clumping of cells and dose dumping may be there 2O

Drug loaded Erythrocytes: This is one of the growing and potential systems for delivery of drugs
and enzymes. Erythrocytes are biocompatible, biodegradable, possess long circulation half life
and can be loaded with variety of biologically aëtive substances. Carrier erythrocytes are
prepared by collecting blood sample from the organism of interest and separating erythroçytes

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from the plasma. By using various physical and chemical methods cells are broken and drug is
entrapped into erythrocytes, finally they are resealed and resultant carriers are then called as
“resealed erythrocytes”. Upon reinjection the drug loaded erythrocytes serve as slow circulation
depots targets the drug to reticulo-endothelial system 21•

Neosomes: In neosomes, the vesicles forming amphiphile is a non-ionic surfactant such as Span
60 which is usually stabilized by addition of cholesterol and small amount of anionic surfactant
such as dicetyl phosphate. Neosomes and liposomes are equiactive in drug delivery potential and
both increase drug efficacy as compared with that of free drug. Neosomes are preferred over
liposomes because the former exhibit high chemical stability and economy. Surfactant forming
neosomes are biodegradable, non-immunogenic and biocompatible. Incorporating them into
neosomes enhances the efficacy of drug, such as nimesulide, flurbiprofen, piroxicam,
ketoconazole and bleomycin exhibit more bioavailability than the free drug 22

Comparison of Neosomes and Liposomes: Neosomes are now widely studied as an alternative to
liposomes, which exhibit certain disadvantages such as —they are expensive, their ingredients
like phospholipids are chemically unstable because of their predisposition to oxidative
degradation, they require special storage and handling and purity of natural phospholipids is
variable. Neosomes are prepared from uncharged single-chain surfactant and cholesterol whereas
liposomes are prepared from doublechain phospholipids (neutral or charged).

Neosomes behave in-vivo like liposomes, prolonging the circulation of entrapped drug and
altering its organ distribution and metabolic stability. Encapsulation of various anti neoplastic
agents in these carrier vesicles has been shown to decrease drug induced toxic side effects, while
maintaining, or in some instances, increasing the anti-tumor efficacy. Such vesicular drug carrier
systems alter the plasma clearance kinetics, tissue distribution, metabolism and cellular
interaction of the drug. They can be expected to target the drug to its desired site of action and/or
to control its release23.

Various typè of drug deliveries can be possible using niosomes like targeting, ophthalmic,

topical, parentral.

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TRANSDERMAL DRUG DELIVERY SYSTEM: Transdermal drug delivery is defined as self

contained, discrete dosage forms which, when applied to the intact skin, deliver the drug, through
the skin at controlled rate to the systemic circulation. Transdermal drug delivery system (TDDS)
established itself as an integral part of novel drug delivery systems Delivery via the transdennal
route is an interesting option because transdermal route is convenient and safe.

The positive features of delivery drugs across the skin to achieve systemic effects are:

•Avoidance of first pass metabolism

•Avoidance of gastro intestinal incompatibility

•Predictable and extended duration of activity

•Improving physiological and pharmacological response

•Termination of therapy is easy at any point of time

•Greater patient compliance due to elimination ‘of multiple dosing profile

•Provide suitability for self administration

•Enhance therapeutic efficacy 24

Sonophoresis is a process that exponentially increases the absorption of topical compounds

(transdermal delivery) into the epidermis, dermis and skin appendages by ultrasonic energy.
Sonophoresis is a localized, non-invasive, convenient and rapid method of delivering low
molecular weight drugs as well as macromolecules into the skin. Mechanistically, sonophoresis
is considered to enhance drug delivery through a combination of thermal, chemical and
mechanical alterations within the skin tissue. Ultrasound at various frequencies in the range of 20
kHz—16 MHz with intensities of up to 3W/cm2 has been used for sonophoresis. Ultrasound
parameters such as treatment duration, intensity, and frequency are all known to affect
percutaneous absorption, with the latter being the most important. Sonophoresis occurs because
ultrasound waves stimulate micro-vibrations within the skin epidermis and increase the overall
kinetic energy of molecules making up topical agents. The ultrasound probably enhances drug
transport by cavitation, micro-streaming, and heating. Ultrasound mediated transdermal delivery

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of key compounds was first reported in 1954 by Fellinger and Schmid through successful
treatment of digital polyarthritis using hydrocortisone ointment in combination with ultrasound.
Sonophoresis is widely used in hospitals to deliver drugs through the skin. Pharmacists
compound the drugs by mixing them with a coupling agent (gel, cream, ointment) that transfers
ultrasonic energy from the ultrasound transducer to the skin. Thus, Application of ultrasoi,ind to
the skin increases its permeability (sonophoresis) and enables the delivery of various substances
into and through the the skin. Sonophoresis is also used in Physical Therapy. Reverse ultrasound
technology may also be used for the extraction of interstitial fluid samples for analysis. So, In
addition to its effects in delivering compounds into the skin, sonophoresis is being investigated
as a way of drawing compounds such as glucose out of the skin 25

Mucoadhesive Drug Delivery Systems: Bioadhesion may be defined as the state in which two
materials, at least one of which is biological in nature, are held together for extended period of
time by interfacial forces. In pharmaceutical sciences, when the adhesive attachment is to mucus
or a mucous membrane, the phenomenon is referred to as mucoadhesion.

The potential of mucoadhesive polymers was shown in ocular, nasal, vagina and buccal drug
delivery systems leading to a significantly prolonged residence time of sustained release delivery
systems on this mucosal membranes. In addition, the development of oral mucoadhesive delivery
systems was always of great interest as delivery systems capable of adhering to certain
gastrointestinal (GI) segments would offer various advantages.
MUCOADHESIVE CARRIER

INTERATION WITH MUCUS

HYDRATION AND SWELL OF POLYMER

DRUG RELEASE

HYDRPPHILLIC MACROMOLECULAR DRUG

CILLARY CLEARANCE ENZYMATIC MATABOLISM

INTERNAL ABSORPTION

FIGURE 5: MECHANISM OF MUCOADIIESION

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Supramolecular Drug Delivery Systems: A supramolecular system is composed of two or more

molecular entities held together and organized by means of intermolecular non-covalent binding
interactions. Supramolecular structures involving macrocyclic compounds have attracted
tremendous interest not only as models for understanding natural supramolecular self-assembly
and molecular recognition, but also as precursors for designing novel nanomaterials for
electronics, biomedical and pharmaceutical applications26.

Osmotically Controlled Drug Delivery Systems: Osmotic pressure is used as driving force for
these systems to release the drug in controlled manner. Osmotic drug delivery technique is the
most interesting and widely acceptable among all other technologies used for the same. Intensive
research has been carried out on osmotic systems and several patents are also published.
Development of osmotic drug delivery systems was pioneered by Alza and it holds major
number of the patents analyzed and also markets several products based on osmotic principle.
These systems can be used for both route of administration i.e. oral and parenterals. Oral osmotic
systems are known as gastro-intestinal therapeutic systems (GITS). Parenteral osmotic drug
delivery includes implantable pumps.

Classification of Osmotic Drug Delivery System: Many forms of osmotic pumps are reported
in the literature but, in general they can be divided in oral and implantable systems.

Osmotic Drug Delivery Devices fall in two categories:

•Implantable:

•Oral osmotic Pump

•The Rose and Nelson Pump

•Higuchi Leeper Pump

•Higuchi Theuwes pump

•Implantable Miniosmotic pump

•Single chamber osmotic pump: Elementary osmotic pump .

•Multi chamber osmotic pump: Push pull osmotic pump, Osmotic pump with non expanding

second chamber

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 A NOVEL DRUG DELIVERY SYSTEM

•Specific types: Controlled porosity osmotic pump, Osmotic bursting osmotic pump, Liquid
OROS, Delayed Delivery Osmotic device, Telescopic capsule, Oroset (colon targeting),
Sandwiched oral therapeutic system, Osmotic pump for insoluble drugs, Monolithic osmotic
system and OSMAT27

ADVANTAGES: Osmotic drug delivery system for oral and parenteral use offer distinct and
practical advantage over other means of delivery. The following advantages contributed to the -
popularity of osmotic drug delivery systems.

•They typically give a zero order release profile after an initial lag.

•Deliveries may be delayed or pulsed if desired.

•Drug release is independent of gastric pH and hydrodynamic condition.

•They are well characterized and understood.

•The release mechanisms are not dependent on drug.

•A high degree of in-vitro and in-vivo correlation (ivivc) is obtained in osmotic systems.

•The rationale for this approach is that the presence of water in git is relatively constant, at least

in tenns of the amount required for activation and controlling osmotically base technologies.

•Higher release rates are possible with osmotic systems compared with conventional diffusion-
controlled drug delivery systems.

•The release from osmotic systems is minimally affected by the presence of food in
gastrointestinal tract.

•The release rate of osmotic systems is highly predictable and can be programmed by modulating
the release control parameters.

DISADVANTAGES

•Expensive

•If the coating process is not well controlled there is a risk of film defects, which results in dose
dumping

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 A NOVEL DRUG DELIVERY SYSTEM

•Size hole is critical

•Dose dumping

•Retrival therapy is not possible in the case of unexpected adverse events.

Microencapsulation: Microencapsulation is the process in which small droplets or particles of

liquid or solid material are surrounded or coated by a continuous film of polymeric materials.
Firstly the microencapsulation procedure was discovered by Bungen burg de Jon and Kan in
1931 and which were deal with the preparation of gelatin spheres and use of a gelatin
coacervation process.

The controlled drug delivery system has used to reduce the problems associated with
conventional therapy and to improve the therapeutic efficacy of a given drug. The maximum
therapeutic efficacy can be achieved by delivering of the active agent in the optimal rate to the
target tissue, then causing little toxicity and minimum side effects.

Microencapsulation process helps for converting the liquids to solids, changing the colloidal and
surface properties, providing environmental protection and controlling the release characteristics
of different coated materials. Some of these properties can be achieved by macropakaging
techniques but in microencapsulation the small coated particles are used to make a wide variety
of dosage forms and has not been feasible.

Novel drug delivery systems which were initiate with the course of optimizing the bioavailability
by the modification of the bioavailability of the drug concentration in blood. With the sustained
and controlled release products, drug therapy can be improved that is the common goal achieved
over with their non sustained and controlled release with the same drug. Microencapsulated
products (micro particles) are the small entities that have an active agent know as the core
material šurrounded by a shell known as the coating material or embedded into a matrix
structure. Most Microparticle shells are of organic polymers, but waxes and lipids are also used.
Generally the size of the microencapsulated products (microparticles) is considered as larger than
1 micrometer and up to 1000 micrometers in diameter. ,

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Commercially available microparticles contained 10- 90% w/w core. A number of core materials
can be encapsulated like that live cells, adhesives, flavors, agrochemicals, enzymes,
pharmaceuticals. The more recent result of pharmaceutical research is that the absorption rate of
a drug can be controlled by controlling its rate of release from the dosage form .The controlled
released dosage forms are so designed and formulated as having the sustained action, sustained
release, prolonged action, delayed action and timed release medication. This has been done by
developing the new drug entities, discovering of new polymeric materials that are suitable for
prolonging the drug release, safety, improvement in therapeutic efficacy.

FIGURE 6: ENCAPSULATION

NDDS IN HERBAL FORMULATIONS In the past few decades, considerable attention has
been focused on the development of novel drug delivery system (NDDS) for herbal drugs. The
novel carriers should ideally fulfill two prerequisites. Firstly, it should deliver the drug at a rate
directed by the needs of the body, over the period of treatment. Secondly, it should channel the
active entity of herbal drug to the site of action. Conventioñal dosage forms Including prolonged

release dosage forms are unable to meet none of these.

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The variety of novel herbal formulations like polymeric nanoparticles, nanocapsules, liposomes,
phytosomes, nanoemulsions, microsphere, transferosomes, and ethosomes has been reported
using bioactive and plant extracts.

MARKET OPPORTUNITIES FOR SR DOSAGE FORM: The global market for advanced
drug delivery systems amounted to $134.3 billion in 2008, and was projected to increase to $139
billion in 2009. The estimate for 2014 is $196.4 billion, for a compound annual growth rate
(CAGR) of 7.2% in the 5-year period. The largest segment of the market is targeted drug
delivery, which reached $50.9 billion in 2009 and is expected to increase to $80.2 billion in
2014, for a CAGR of 9.5%.Sustained-release products have the second-largest market share,
with estimated sales of $36.1 billion in 2009 and $45.8 billion in 2014, for a CAGR of 4.9%.
Benefits for short half-life drugs, sustained release can mean less frequent dosing and thus better
compliance reduce variations3 in plasma/blood levels for more consistent result28.

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CONCLUSION:

Novel drug delivery system have been used in a broad range of pharmaceutical applications. It
has enhanced drug to disease locations with short duration of time and are now clinically
excepted.

Also, it promotes targeting of particular diseased cells within the disease site. Finally, it has
exhibited reduced toxicity’ s and increase efficacy with free convection drugs. Only time will tell
which of the above applications and speculations will proof to be successful.

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REFERENCES:

1. NagashreeK.,Department of Pharmaceutics, MNR college of pharmacy, Hyderabad, India.

2.Reddy. P.D., SwarnalathaD.Recent advances in Novel Drug Delivery Systems. IJPTR, 2010;

2(3): 2025-2027.

3 .Muller.C.C. “Physicochemical characterization of colloidal drug delivery systems such as

reverse micelles, vesicles, liquid crystals and nanoparticles for topical administration”, European
Journal of Pharmaceutics and Biopharmaceutics. 2004; 58(2): 343-3 56.

4.http://www.azonano.comloars.asp

4.Aminabhavi T.M. JCR. 2001; 70; 1-20

5.Manivannan R. Recent Advances In Novel Drug Delivery System. IJRAP. 2010; 1(2); 3 16-
326

6.Lobl Ti, Schloss JV, Nagy AI, Pananen JE, kiventors; Neurosystec corporation, Valencia CA,
Assignee; Nanoparticle Drug Formulation. US Patent 20080145439. 2008 June 19.

7.O’Neil, Jacklyn, “Controlling drug delivery for the application of extended or sustained-release
drug products for parenteral administration”. Chemistry Master’s Theses. 2010; Paper 14.

8.Sahoo C.K. An overview on resealed erythrocytes:Anovel approach to drug delivery. IJPPS.

2012; 4(2);

9.Gupta A. Cell based drug delivery system through resealed erythrocyte-A review. IJPSDR.
2010; 2(1); 23-30.

1 0.Magnáni M, Rossi L, Biagiotti S, Bioanchi M, Inventors; Drug Delivery System. US Patent

20120141540. 2012 June 7.

11 .Grimald S, Lisi A, Cinti C, Inventors; CNR ConciglioNazionaleDelleRicerche Roma,

Assignee; US Patent 20110262415. 2011 Oct 27.

12.Yang VC, Kwon YM, Chung HS, Yang AJ, Inventors; Erythrocyte encapsulated L aspaginase
for enhanced acute Lymphoblastic Leukemia Therapy. US Patent 20100284982. 2010 Nov 11.

23
 A NOVEL DRUG DELIVERY SYSTEM

1 3.Madhar NVS, Saini A. Niosomes: A novel drug delivery system. IJRPC. 2011; 1(3); 498- 11.

14.Nisato G BaretJC,Inventors; Koninklijke Philips Electronics N.V, NC, Assignee; Transdermal

Drug Delivery Patch. US Patent 20100222751. 2010 June 10.

15.Heiati H, Weimann L, Inventor; Pharmapatch LLC, San Diego,CA,Assignee;Multiple Nozzle

Transdermal Drug Delivery System. US Patent 20100143448. 2010 Sept 2.

16. Vinod KR., Reddy R., Banji D., Reddy V., Sandhya S. Critical review on mucoadhesive drug
delivery systems. Hygeia journal for drugs and medicines. 2012; 6(1); 7-28.

17.Hee Jae yoon, Woo Dong Jang. Polymeric supramolecular systems for drug delivery. JMC.
2010; 2; 211-222.

18.Zerbe HG, Paiement N, Inventor; Oral Mucoadhesive Dosage form. US Patent 20110028431.
2011 Feb 3.

19.Gupta S., Singh R.P., Sharma R., Kalyan’ at R., Lokwani P. Osmotic pumps: A Review.
IJCP. 2011; 6(1); 1-8.

20.Patel H., Pate! U., Kadikar H., Bhimani B., Daslaniya D., Pate! G. A review on osmotic drug
delivery system. IRJP. 2012; 3(4); 88-94.

21.Nghiem T, Jackson G,Invçntors; Biovail Laboratories International S.R.L., Assignee;

Multiparticulate Osmotic Delivery System. US Patent 20090004281. 2009 Jan 1.

22.Patel HB, Inventor; Reliant pharmaceuticals INC., Assignee; Oral Osmotic Drug Delivery
System. US Patent 20080248114. 2008 Oct 9.

23.Kidane A, Bhatt PP, Inventors; Osmotic Drug Delivery System. US Patent 20070254032.
2007 Nov 1.

24.Kumar A., Sharma P., Banik A. Microencapsulation as novel drug delivery system.
InternatjonalePharmaceuticaSciencia. 2011; 1(1); 1-7.

25.Saraf A.S. Applications of novel drug delivery system for herbal formulations. Fitoterapia.
2010;81;680-689.

24 .
 A NOVEL DRUG DELIVERY SYSTEM

26.He ZF, Liu DY, Zeng S, Ye JT. Study on preparation of ampelopsin liposomes. Journal Chine
Mat Med. 2008; 33(1); 27-30.

27.Rane S, Prabhakar B. Influence of liposome composition on paclitaxel entrapment & Ph

sensitivity of liposomes. IJPTR.2009; 1(3); 914-917.

28.Youfang C., Xianfu L., Hyunjin P., Richard G. Artemisnin nanoparticles.

NanomedNanotechnolBiol Med. 2009; 5; 3 16-322

25