ABSTRACT

Now day’s Recent advances in the understanding of pharmacokinetic & pharmacodynamic

behaviour of drug have offer a more rational approach to the development of optimal drug
delivery system. Now it's appreciable that future success in Drug delivery research will largely
be result of multidisplinary efforts. If any therapeutic agent that can be the more efficacious and
safe using and improved drug delivery system represent both lucrative marketing opportunities
for pharmaceutical company and advancement in the treatment of diseases of mindkind. An
ideally design drug delivery system delivers a specified amount of drug to target particular site at
an appropriate time and rate as dictated or desired by the etiological and physiological needs of
the body. Conventional Pharmaceutical Dosage forms are incapable of controlling the rate of
drug delivery to target site. As a result the distribution of drug in nontarget tissue and body fluids
necessitate therapeutic doses that could far exceed the amount required in target cells, the higher
doses often lead to serious adverse during treatment thus, the novel drug delivery systems
(NDDS) are carriers which maintain the drug concentration in therapeutic range for longer
period of time and also, in addition, may deliver the content to the site of action if so desired as
per requirements.

KEYWORDS
Drug delivery systems, therapeutic agent, diseases, target site, body fluids, non- targeting tissues,
drug etc.

INTRODUCTION
Novel drug delivery systems is the new system Recent advances in the understanding of
pharmacokinetic & pharmacodynamic behaviour of drug have offer a more rational approach to
the development of optimal drug delivery system. the novel drug delivery systems (NDDS) are
carriers which maintain the drug concentration in therapeutic range for longer period of time
There are several advantages of novel drug delivery systems over conventional drug delivery.

1. Optimum therapeutic- drug concentration in the blood or in tissue may be maintained over a
prolonged period of time.

2. Pre- determined release rates of extended period of time may be achieved.

3. Duration for short half- life drug may be increased.

4. By targeting the site of action, side effects may be eliminated.

5. Frequent dosing and wastage of the drug may be reduced or excluded. 6. Better patient
compliance may be ensured.

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Novel drug delivery systems
• Sustained- or controlled- drug delivery systems provide drug action at a pre determined rate by
providing a prolonged or constant (Zero-order) release respectively, at the therapeutically
effective levels in the circulation.

• Localized drug delivery devices provide drug action through spatial or temporal control of drug
release (usually rate- limiting) in the vicinity of the target.

• Rate- pre-programmed drug delivery systems provide drug action by manipulating the release
of drug molecules by system design which control the molecular diffusion of drug molecules.

• Targeted drug delivery provides drug action by using carries either for passive or active
targeting or one base or self programmed approach, usually anchored with suitable sensory
devices, which recognize their receptor at the target.

Table 1.0 Classification of sustained or controlled release system based on

their rate – controlled mechanism.

Type of System Rate control Mechanism

Diffusion – controlled
Reservoir systems (Ocusert) Diffusion through membrane
Monolithic systems (Transdermal drug) Diffusion through membrane
Delivery system- Nitro -dur)
Water penetration controlled
Osmotic systems (Oros, Alzet osmotic Osmotic transport of water through
pump) semi-permeable membrane
Swelling system( hydrogel ) Water penetration into glassy polymer
Chemically - controlled
Pendent systems Combination of hydrolysis of pendent
group diffusion from bulk polymer
Ion – exchange resins Exchange of acidic or basic drug with
the ions present on resins

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 Fig 1.0: Schematic depiction of various classes of controlled release system.

Carrier system for the targeted and controlled drug delivery purpose may be classified on the
basis of their nature, mechanism of drug release and nature drug incorporation. (Table 1.0 and
Fig . 1.0 ) Diffusion occur when bioactive agent is hydrophilic and passes through the polymer,
the key building block and controlled release concept. Many environmentally – responsive
system are also designed that retains their content until appropriately placed in biological by an
environment and are activated by an external or internal stimulus for the release of drug. Show
the mechanism of drug release from various drug – delivery systems.

Reservoir- Type drug delivery system

In the reservoir- type drug delivery systems, drug is encapsulated in the drug reservoir
compartment whose drug – releasing surface is covered by a rate- controlling an embryonic
polymer membrane.

The drug in the reservoir compartments can be drug in liquid – or solid type dispersion of drug in
a liquid or solid type dispersion medium. The polymeric membrane can be fabricated from a
homogeneous or heterogeneous non – porous polymeric material or semi- permeable membrane.
The release of drug from this type of delivery system occurs at a nearly constant rate (Q/ t).

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Ocusert
A truly continuous, controlled- release and zero – order kinetic fashion was achieved using
ocusert. First marketed by Alza Corporation, California, the pilocarpine ocusert improved the
non complience problems, low intra -ocular drug bioavailability and potential systemic side
effect of pilocarpine. The systems consist of a pilocaroine-aliginate core of (drug) sandwiched
between two transparent rate – controlling ethylene- venyl acetate co- polymerbased thin
membrane. When this is placed under the upper eyelid, The pilocaroine molecules after getting
dissolved in the lachrymal fluid are released through the rate controlling membranes at a pre
programmed rate.

A mixture of pilocarpine and alginic acid in the drug reservoir releases the drug for almost one
week. A thin membrane of ethylene venyl acetate (EVA) co polymer encloses the reservoir
above and below. A retraining ring of the same material impregnated with titanium dioxide
encloses the drug reservoir circumferentially (fig.1.1).

NOVEL CARRIER FOR CONTROLLED & TARGETED DRUG

DELIVERY
As the knowledge of the molecular biology and pathophysiology of diseases has expanded, more
therapeutically precised and purpose specific drug are being developed. These newly developed
drug have high potency (low therapeutic window) and required their localization of the particular
site of their action. Most drugs are administrated by conventional immediaterelease dosage
forms. They distribute freely throughout the body & accumulate the non – specific organs in an
undesirable manner and thus produce adverse side effects. To reduce these slides and increased
their therapeutic benefits, they should be delivered to their respective site of action, and hence
suitable carrier systems becomes mandatory requirement. Various novel carriers have been
developed for the purpose. Among these colloidal carriers such as liposomes, nano- particles &
supra molecular system, i.e. micelles have gained more attention in the field of controlled and
targeted drug delivery. Recently new carriers such as inorganic particles, liquids crystal,

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aquasomes, carbon nano tubes, dendrimers etc. Are also investigated for the specialized purpose.
In the following section, these carriers for the same purpose are brief.

Colloidal carrier

Liposomes
Liposomes were discovered in the early 1960s by Bingham and co-workers and subsequently
became the most extensive- explored drug -delivery system. Initially, through they were used to
study in vitro simulated – biomembrane behaviour, subsequently, they enraged as strong
therapeutic tools most notably in drug delivery and drug targeting.

Structurally, liposomes are phospholipid -based colloidal vesicular structures in which

hydrophilic core is entirely enclosed by membranous lipid bilayer’s. They may be classified on
the basis of method of preparation, structural perameters or special function.

Nanosomes
Non – ionic surfactants vesicles (niosomes) or NSVS) are now widely studied as an alter - native
to liposomes. Non -ionic surfactants vesicles results from the self- assembly of hydrated
surfactants monomers. Non – ionic surfactants of wide variety of structural types have been
found to be useful alternatives to phospholipids. Through the terminology suggests that
distinctions exist between niosomes and liposomes of which the former is having chemical
differences in the monomers units, niosomes posses physical properties, which are similar to
liposomes, which are formed from phospholipids. As the name indicated, generally non- ionic
surfactants vesicles are prepared by the incorporation of components containing non- ionic
surfactants. However, they may also prepared with various ionic amphiphiles such as
dicetylphosphate, stearylamine, etc. In order to achieve a stablevasicular suspension. It is
important to identify and know the basic structural units of NSVs. while an amphiphilic head
groups. The vesicles forming non-ionic compounds are mainly alkyl ether lipids. These can be
broadly divided into two classes based on nature of their hydrophilic head groups, i.e. Alkyl
ethers in which the hydrophilic head group consists of repeat glycerol subunits, related isomers
or larger sugar molecules, and those in which the hydrophilic head group consists of repeat
ethylene oxide subunits. In addition, alkyl esters, amides and fatty acids, and amino acids
compounds also from vesicles.

The ultimate identity of any niosomal system and hence its properties are determined by the
factors listed in Fig. 1.2. It is thus obvious that all these variables must be carefully controlled in
the design of a niosomal drug -delivery system.

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 Fig. 1.2: Factors influencing niosomes physical stability.

Although pharmaceutical niosomes formulations have yet to be commercially exploited, a

number of studies have demonstrated the potential of niosomes in drug delivery. Niosomes have
been proven to be useful in the delivery Of anti-infective agents, anti- cancer agents, anti-
inflammatory agents, and fairly recently, as a vaccine adjuvants. These systems have been
proven to target certain areas of the mammalian anatomy and may be exploited as a diagnostic
imaging agents.

Examination of the literature reveals that on IV administration of niosomes, the highest drug
level are found in the liver. However, there were exceptions. When DOX 850 nm C16G3
niosomes were administrated, DOX liver levels are although low (~0.5% of administrated dose
10 nm after dosing) in case solution administration, they are higher for noisome formulation. The
cause of this non-liver uptake is not apparent although smaller DOX niosomes are found to
accumulate in the liver following IV administration.

Microparticles
The” microcapsules “are defined as a spherical particles with size varying from 50 nm to 2nm,
containing a core substance. Microspheres are, in real sense, spherical empty particles. However,
the term microcapsules & microspheres are often used interchangeably. In addition some releted
terms are used as well for example, “microbeads” & “beads” are used alternatively. Sphere and
spherical particles are also used for particles of large size & rigid morphology. The dried
microspheres from free flowing powders .they consist of proteins or synthetic polymers, which
bio degradable & ideally have a size range less than 200 ųm. The solid bio degradable
microspheres bearing a drug dispensed or dissolved throughout particles matrix have potential in
controlled- release of drugs.

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 These carriers received much attention not only prolonged- release formulations but also for the
carrier potential in drug targeting particularly anti- cancer drugs the tumour.

Pre-requisites for ideal micro particulate carriers are follows.

•Longer duration of action

•control of drug release

•Increase of therapeutic efficiency

•Protection of drug

•Biocompatibility

•Relative stability

•water -solubility or Dispensability

•Bioresorbability

•Targetability

•Polyvalency

Microspheres can be prepared by using any of appropriately selected method including in situ
polymerization, solvent evaporation, coacervation phase separation, spray drying and spray
congealing, etc., but the choice of techniques depends on the nature of the polymer used, the
drug, the intended use and duration of therapy. The choice of method is depend on the following
Determinants.

1. The particles size requirements.

2. The drug or the protein should not be adversely affected by the process.

3. Reproducibility of the release profile and the method.

4. No stability Problem.

5. There should be no toxic product associated with the final product.

A number of different substances both biodegradable as well as non- biodegradable have been
investigated for the preparation of microspheres.

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These materials include the polymer of natural synthetic origin and also modified natural
substances. Synthetic polymers employed as carriers materials are methyl methacrylate, acrolein,
lactide, Glycolide and their co-polymers, ethylene vinyl acetate copolymer, polyanhydrides etc.

The natural polymers used for the purpose include albumin gelatin, starch, collagen &
carrageenan, etc.

APPLICATIONS OF NOVEL DRUG DELIVERY SYSTEMS

Sustained and controlled- drug delivery

Controlled release of drug or encapsulated bioactives could be achieved using NDDS. Desired
release pattern will definitely improve the pharmacokinetics and hence pharmacodynamics of
drug. The controlled delivery of antibiotics in the treathment of H. Pylori via NDDS is an
effective process compared to conventional one. Similarly, slow and sustained release oF drug
from implants avoids regular administration of drug hence ensures patients compliance.
Numerous applications of NDDS is sustained and controlled delivery of drug are enumerated.
Some of them have already been discussed in preceeding sections.

Deport formulations of short -acting peptides have been successfully developed using
microparticle technology. Such peptides include leuprorelin acetate and triptoreline, Both
lutenizing harmone releasing hormone agonist. Leuprorelin polylactided acid co-glycolide
microspheres may be used as a monthly and three monthly dosage forms in the treatment of
advancement prostrate cancer, endometriosis and other hormone responsive conditions. These
microspheres effectively halt the progression of prostate cancer or endometeriosis in patients and
are currently marketed as prostap SR.

Other peptides formulated as sustained release microparticles include the angiotensin receptors-
antagonist, L -158809, for the treatment of hypertension, thyrotropin releasing hormone for
central nervous system stimulation, salmon calcitonin for the treatment of hypercalcemia or
postmenopausal oeteoporosis and the immunosuppressant drug cyclosporin A. There are no. Of
products available in the market for clinical studies as listed in Table 1.1.

Table 1.1: list of various marketed formulations based on novel drug delivery systems.

DRUG INDICATION COMPANY NAME

Dexorubicin Kaposi’s sarcoma SEQUUs
Daunorubicin Advanced kaposi’sarcoma NeXstar
Amphotericin B Systemic fungal infection NeXstar
Amphotericin B Systemic fungal infection SEQUUS
Leuprolide acetate Prostate cancer Takeda-Abott
Triptorelin LHRH agonist Novartis

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CONCLUSION
Novel Drug delivery System (NDDS) NDDS is a combination of advance technique and new
dosage forms which are far better than conventional dosage forms. Advantagesof Novel Drug
Delivery System are: Optimum dose at the right time and right location, Efficient use of
expensive drugs, excipients and reduction in production cost, Beneficial to patients, better
therapy, improved comfort and standard of living. Basic modes of novel drug delivery systems
are: Targeted Drug Delivery System, Controlled Drug Delivery System etc.

Novel Drug delivery & drug targeting is new techniques which is used in pharmaceutical
science. Like targeting drug delivery, vaccine delivery, Gene therapy, commercial development
of novel carries (liposomes).

Future prospects
Targeting drug delivery is the major focus of current research. After the concept of magic bullet,
only a few targeted formulations could reach to market. The discovery of area of molecular
biology, biotechnology & pharmacogenomics regularly demand the practical key issues of
targeting of biomolecules to the center of attention. Like Tumour targeted drug/ gene delivery is
the most demanded therapeutic requirements of the coming Future.

REFERENCE

1. Roop k khar, s.p vyas, farhan j ahmed, gaurav k jain “the theory and practice of industrial
pharmacy “4th edition lachman’s/lieberman’s cbs distributors, 2013; 872, 902, 905, 943.

2. Charman w.n, chan k, finnin BC & chairman SA drug delivery: a key factor in realising the
full therapeutic potential of drug. Drug development research, 1999; 46: 316-27.

3. Santini JT, Richards Ac, scheidt R, cima MJ and longer R. Microchips as controlled drug
delivery devices angew chem. Int. Td, 2000; 39: 23, 96-407.

4. Kopeek J. Smart & genetically engineered biomaterials & drug delivery systems. European
journal pharmaceutical science, 2003; 20: 1-16.

5. Torchilin v.p structure & design polymeric surfactant- based drug delivery systems, journal of
controlled release, 2001; 73: 137-172.

6. Haag R. Supramolecular Drug-Delivery Systems based on Polymeric Core-Shell

Architectures. Angew. Chem. Int. Ed, 2004; 43: 278-82.

NGI College of Pharmacy, Meerut Page 9

7. Bae Y, Fukushima S, Harada A and Kataoka K, Design of Environment-Sensitive
Supramolecular Assemblies for Intracellular Drug Delivery. Polymeric Micelles that are
Responsive to Intracellular pH Change. Angew. Chem. Int. Ed, 2003; 4640: 42-43.

8. Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE. Biodegradable polymeric
nanoparticles as drug delivery devices. Journal of Controlled Release, 2001; 70: 1-20.

9. Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro
and nanoparticles in drug delivery. Journal of Controlled Release, 2004; 100: 5-28.

10. lByrne ME, Park K, Peppas N. Molecular imprinting within hydrogels, Advanced Drug
Delivery Reviews 2002; 54: 149-61.

11. Sood A and Panchagnula R. Peroral Route: An Opportunity for Protein and Peptide Drug
Delivery.Chemical Reviews, 2000; 101: 3275-303.

12. Niculescu-Duvaz I, Springer CJ. Antibody-directed enzyme prodrug therapy (ADEPT): a

review. Advanced Drug Delivery Reviews, 1997; 26: 151-72.

13. Alvarez-Lorenzo C, Concheiro A, Molecular imprinted polymers for drug delivery. Journal
of Chromatography, 2004; 804: 231-45.

14. Winterhalter M, Hilty C, Bezrukov S M, Nardin C, Meier W, Fournier D. Controlling

membrane permeability with bacterial porins. Applications to encapsulated enzymes. Talanta
2001; 55: 965-71.

15. Jiang W, Kim BY, Rutka JT, Chan WC. Expert Opin. Drug Delivery 2007; 4: 621- 633.

16. Bonard JM, Kind H, Stockli, Nilsson LA. Field Emission from Carbon Nanotubes: The First
Five Years. Solid-State Electronics 2001; 45: 893 – 914.

17. Ajayan PM. Nanotubes from Carbon, Chem. Rev. 1999; 1787–99.

18. Dresselhaus MS, Dresselhaus G, Eklund PC. Science of Fullerenes and Carbon Nanotubes.
Academic Press; New York, 1996.

19. Santini JT, Richards AC, Scheidt R, Cima MJ, Langer R. Nature, 1999; 397: 335.

20. P. Dario, MC Carrozza, A Benvenuto, A Menciassi, J Micromech. Microeng, 2000; 10.

21. Bruguolle B, Lemmer B. Recent advances in Chrono pharmacokinetics “methodological

problems. Life Sci, 1993; 52: 1809-1824.

22. Lalla J K, Mamania, H M. Indian J. Pharm. Sci, 2004; 59(4): 23-26.

23. Corveleyn S, Remon, JP. Int. J. Pharm, 1997; 152: 215-225.

NGI College of Pharmacy, Meerut Page 10

24. Tomalia DA, Reyna LA, Svenson S: Biochem. Soc. Trans, 2007; 35: 61-67.

25. Szoka F. Annu. Rev. Biophys. Bioeng, 1980; 9: 467-508.

26. Toth E, Bolskar RD, Borel A et al. J. Am. Chem. Soc, 2005; 127: 799-805.

27. Bolskar RD, Benedetto AF, Husebo LO et al. J Am. Chem. Soc, 2003; 125: 5471-5478.

28. Sitharaman B, Tran LA, Pham QP et al. Contrast Media Mol. Imaging, 2007; 2: 139-146.

29. Kamal Singh Rathore, Rohit lowalekar, Nema RK, The Pharma Review, 2006; 30-32.

30. Chan WCW: In: Bio-Applications of Nanoparticles. 2007, Landes Bioscience, Austin, TX,
USA.

NGI College of Pharmacy, Meerut Page 11