approach on novel drug delivery system

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Kagalkar et al. World Journal of Pharmacy and Pharmaceutical Sciences

REVIEW: APPROACH ON NOVEL DRUG DELIVERY SYSTEM

Kagalkar A. A*, Nitave S. A.

Anil Alias Pintu Magdum Pharmacy College, Dharangutti, India.

ABSTRACT

Tremendous advancements in drug delivery, oral administration of

therapeutic agents still remains the favored route for majority of

clinical applications, due to the excellent accessibility, and patient

compliance as well as the preferred alternative route of drug

administration for non-invasive drug delivery among the other various

routes is Novel drug delivery system. The correlation between drug

intake and a clinical response is complex enough, the choice and

design of the ideal pharmaceutical dosage form of a drug delivery

system would be critically important to reach a progress in superior

drug development. 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.

Key words: Drug delivery systems (DDS), controlled release (CR).

INTRODUCTION

The method by which a drug is delivered can have a major 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, very slow development 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 effectiveness

of drugs were generated. These new strategies, often called drug delivery systems (DDS), are

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Article Received on 03 August 2013, Revised on 30 August 2013, Accepted on 26 September 2013

*Correspondence for

Author:

* Amrita Kagalkar

Anil Alias Pintu Magdum

Pharmacy College,

Dharangutti, India.

[email protected]

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based on interdisciplinary approaches that merge polymer science, pharmaceutics,

bioconjugate chemistry, and molecular biology [1].

Oral route of administration is one of the oldest and most widely used routes for the

administration of drug providing convenient method of efficiently achieving both local and

systemic effect. In conventional drug delivery systems, there is little or no control over

release of the drug and effective concentration at the target site can be achieved by irregular

administration of grossly excessive doses. This kind of dosing pattern result is frequently

changing, erratic and sub or supra therapeutic plasma concentrations, leading to marked side

effects in some cases [2].

The rate and extent of absorption of drug from conventional formulations may vary greatly

depending on factors such as physicochemical properties of the drug, presence of excipients,

various physiological factors such as presence or absence of food, pH of gastro intestinal

tract, gastro intestinal motility and so on. Uncontrolled rapid release of drug may also cause

local gastro intestinal or systemic toxicity. Hence better dosage form design and delivery can

minimize many of these problems. Various approaches are made in designing the

formulations, which will overcome the disadvantages of conventional dosage forms, which

include sustained/controlled drug delivery system. There are three main categories of

controlled-release drug delivery system namely Intravenous, Transdermal, and Oral systems.

Oral osmotically controlled release (CR) delivery system provide a uniform

concentration/amount of drug at the site of absorption and thus after absorption, allow

maintenance of plasma concentration within therapeutic range, which minimizes side effects

and also reduces the frequency of administration[2].

Carrier-mediated drug delivery has emerged as a powerful methodology for the treatment of

various pathologies. The therapeutic index of traditional and novel drugs is enhanced by the

increase of specificity due to targeting of drugs to a particular tissue, cell or intracellular

compartment, the control over release kinetics, the protection of the active agent or a

combination of the above. Among various systems considered for this approach. The

development of novel drug delivery techniques has got its own specific challenges. The

selection of the route of administration and the dosage form has to integrate therapeutic

considerations, drug substance properties, selection of excipients technical formulation

feasibility and patient needs. The pharmaceutical industry is altering day to day based on the

varying patient requirements and global developments. The industries have diverted their

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research focuses from conventional dosage forms to novel drug delivery technologies which

has got significantly improved market requirements. In recent years the pharmaceutical

companies are struggling to maintain a balance between the downward pressure on prices and

significantly raised innovation cost. It is going to be always a green zone for companies

developing novel delivery technologies to maintain their market presence and share. The

introduction of novel delivery systems to an existing molecule should significantly improve

its safety, efficacy and improved patient compliance. Most of the innovator companies have a

parallel research pipeline for biopharmaceuticals and concentrates on protein-peptide base

drug portfolio [3].

The method by which a drug is delivered can have a significant effect on its efficacy. Some

drugs like Ginseng and Rosemary 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, very slow progress in the efficacy of

the treatment of severe diseases has recommended a growing need for a multidisciplinary

approach to the delivery of therapeutics to targets in tissues. Keeping in view the above facts

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) are based on interdisciplinary approaches that

combine polymer science, pharmaceutics, bioconjugate chemistry and molecular biology. An

ideal drug delivery system possesses two elements (i) ability to target (ii) to control the drug

release. Targeting will make sure high efficiency of the drug and reduce the side effects

especially when dealing with drugs that are presumed to kill cancer cells but can also kill

healthy cells when delivered to them. The prevention of side effects is achieved by controlled

release of drug. Therefore, different types of delivery system are used for variety of synthetic

drugs, phytomolecules and herbal extracts to ensure better bioavailability and targeted

delivery. Some of these delivery systems are Cubosomes, Colloidosomes, Ethosomes,

Aquasomes, Niosomes, Liposomes and Nanoparticles[4].

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 [5].

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Different types of NDDS

1. Liposomes: Liposomes are small artificial vesicles of spherical shape that can be created

from cholesterol and natural nontoxic phospholipids. Due to their size and hydrophobic

and hydrophilic character, liposomes are promising systems for drug delivery. Liposome

properties differ considerably with lipid composition, surface charge, size, and the

method of preparation. It has been displayed that phospholipids impulsively form closed

structures when they are hydrated in aqueous solutions. Such vesicles which have one or

more phospholipid bilayer membranes can transport aqueous or lipid drugs, depending on

the nature of those drugs. Because lipids are amphipathic in aqueous media, their

thermodynamic phase properties and self assembling characteristics influence

entropically focused confiscation of their hydro-phobic sections into spherical bilayers.

Those layers are referred to as lamellae. Generally, liposomes are definite as spherical

vesicles with particle sizes ranging from 30 nm to several micrometers. They consist of

one or more lipid bilayers surrounding aqueous units, where the polar head groups are

oriented in the pathway of the interior and exterior aqueous phases. On the other hand,

self-aggregation of polar lipids is not limited to conventional bilayer structures which rely

on molecular shape, temperature, and environmental and preparation conditions but may

self-assemble into various types of colloidal particles [6].

Fig 1: Structure of liposme.

Advantages

Some of the advantages of liposome are as follows:

• Provides selective passive targeting to tumor tissues (Liposomal doxorubicin).

• Increased efficacy and therapeutic index.

• Increased stability via encapsulation.

• Reduction in toxicity of the encapsulated agents.

• Site avoidance effect.

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• Improved pharmacokinetic effects (reduced elimination, increased circulation life times).

• Flexibility to couple with site specific ligands to achieve active targeting.

General Method of Preparation and Drug Loading:

Liposomes are manufactured in majority using various procedures in which the water soluble

(Hydrophilic) materials are entrapped by using aqueous solution of these materials as

hydrating fluid or by the addition of drug/drug solution at some stage during manufacturing

of the liposomes. The lipid soluble (lipophilic) materials are solubilized in the organic

solution of the constitutive lipid and then evaporated to a dry drug containing lipid film

followed by its hydration. These methods involve the loading of the entrapped agents before

or during the manufacturing procedure (Passive loading). However, certain type of

compounds with ionizable groups, and those which display both lipid and water solubility can

be introduced into the liposomes after the formation of intact vesicles (remote loading) [7].

Fig 2: General method of liposomes preparation and drug loading.

2. Colon delivery: Colon delivery refers to targeted delivery of drugs into the lower GI

tract, which occurs primarily in the large intestine (i.e. colon). The site specific delivery of

the of drugs to lower parts of the GI tract is advantageous for localized treatment of several

colonic diseases, mainly inflammatory bowel disease (Crohn’s disease and ulcerative colitis),

irritable bowel syndrome, and colon cancer. Other potential applications of colonic delivery

include chronotherapy, prophylaxis of colon cancer and treatment of nicotine addiction. It has

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also gained increased importance not just for the delivery of drugs for the treatment of local

diseases, but also potential site for the systemic delivery of therapeutic proteins and peptides

which are being delivery by injections. The colon is a ‘‘friendlier’’ environment for proteins

and peptides compared to the upper part of GI tract. Clinically relevant bioavailability may be

achieved if the peptide can be protected from acid and enzymes in the stomach and upper

intestine.

Advantages of CDDS over Conventional Drug Delivery

Chronic colitis, namely ulcerative colitis, and Crohn’s disease are currently treated with

glucocorticoids, and other anti- inflammatory agents.

Administration of glucocorticoids namely dexamethasone and methyl Prednisolone by

oral and intravenous routes produce systemic side effects including adenosuppression,

immunosuppressant, cushinoid symptoms, and bone resorption.

Thus selective delivery of drugs to the colon could not only lower the required dose but also

reduce the systemic side effects caused by high doses.

Colon specific drug delivery has gained increased importance not just for delivery of the

drugs in the treatment associated with the colon, but also as a potential site for the systemic

delivery of therapeutic peptides and proteins. To achieve successful colon targeted drug

delivery, a drug need to be protected from degradation, release and absorption in the upper

portion of the GI tract and then to be ensured abrupt or controlled release in the proximal

colon. This review mainly compares the primary approaches for CDDS (Colon Specific Drug

Delivery) namely pro-drugs, pH and time dependent systems, and microbial triggered

systems, which achieved limited success and had limitations as compared with newer CDDS

namely pressure controlled colonic delivery capsules, CODESTM, and osmotic controlled

drug delivery (ORDS-CT) which are unique in terms of achieving in vivo site specificity, and

feasibility of manufacturing process [8].

Fig 3: Design of enteric coated timed-release press coated tablet (ETP Tablet).

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3. Cubosomes: Cubosomes are the biocompatible novel approach for the drug delivery

system. The controlled release application of these nanoparticles is of a great significance in

cosmeceutical and pharmaceutical fields. Low cost of the raw materials, flexibility and the

potential for controlled release through functionalization makes them an attractive vehicle for

several in-vivo drug delivery routes. Precursor forms of cubosomes are among the

modification possible to overcome its difficulty in loading of drugs. Cubosomes are the

square and rounded particles with internal cubic lattices visible [9].

Cubosomes are discrete, sub-micron, nanostructured particles of bi-continuous cubic liquid

crystalline phase. Cubosomes are typically produced by high-energy dispersion of bulk cubic

phase, followed by colloidal stabilization using polymeric surfactants. Cubosomes offer a

large surface area, low viscosity and can exist at almost any dilution level. They have high

heat stability and are capable of carrying hydrophilic and hydrophobic molecules. Combined

with the low cost of the raw materials and the potential for controlled release through

functionalization, they are an attractive choice [9].

Bi-continuous cubic phases are optically isotropic, very viscous, and solid like liquid

crystalline substance with cubic crystallographic symmetry. Bicontinous cubic phases consist

of two separate, continuous but non-intersecting hydrophilic regions divided by a lipid

bilayer in to a periodic minimal surface with zero curvature. The bicontinuous nature of such

cubic phases differentiates them from the so-called micellar or discontinuous cubic

containing micelles packed in cubic symmetry [10].

Two main approaches are used to produce cubosome particles. The top-down approach

applies high energy to fragment bulk cubic phase. The bottom-up approach forms cubosomes

from molecular solution by, for example, dilution of an ethanol-monoolein solution. Top-

down or high-energy techniques require formation of cubosomes prior to their use in a

product. Bottom-up techniques avoid high-energy drawbacks and allow formation of

cubosomes in use by a consumer or during product formulation. Both techniques require a

colloidal stabilizer, like the tri-block copolymer Poloxamer 407, to prevent cubosome

aggregation. Cubosome formation by any method, even dispersion of bulk cubic phase,

requires some time for the viscous cubic phase to crystallize from less-ordered precursors.

The mechanism of cubosome formation by high energy dispersion is clearly the

fragmentation of bulk cubic phase into smaller pieces. The dilution process produces

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submicron cubosomes in the absence of fluid shear by dilution of an isotropic liquid

precursor, but the exact cubosome formation mechanism is not known [11].

Fig 4: Cubosomes

4. Colloidosomes: The capsules are fabricated by the self-assembly of colloidal particles

onto the interface of emulsion droplets. After the particles are locked together to form elastic

shells, the emulsion droplets are transferred to a fresh continuous-phase fluid that is the same

as that inside the droplets. The resultant structures, which we call “colloidosomes,” are

hollow, elastic shells whose permeability and elasticity can be precisely controlled. The

capsule surfaces are composed of a close-packed layer of colloidal particles, linked together

to form a solid shell; the interstices between the particles form an array of uniform pores,

whose size is easily adjusted over the nanometer to micrometer scale to control the

permeability [12].

Colloidosomes are used as advanced tool for encapsulation of various materials such as

drugs, dyes, cosmetics, biomaterials as filler in catalysis and waste removal. Conventional

methods of preparing a core particle include capillary-based micro fluidic techniques,

precipitation polymerization techniques and inverse suspension polymerization techniques [13].

Fig 5: Colloidosomes

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5. Ethosomes: Ethosome are novel carrier system used for delivery of drugs having low

penetration through the biological membrane mainly skin. Ethosomes are the slight

modification of well established drug carrier liposome. Ethosomes are lipid vesicles

containing phospholipids, alcohol in relatively high concentration and water. Ethosomes are

soft vesicles made of phospholipids and ethanol and water. The size range of ethosomes may

vary from tens of nanometers to microns (µ). Ethosomes permeate through the skin layers

more rapidly and possess significantly higher transdermal flux in comparison to conventional

liposomes. Ethosomes provides a number of important benefits including improving the

drug’s efficacy, enhancing patient compliance and comfort and reducing the total cost of

treatment [14].

Fig 6: Ethosomes

Advantages of ethosomal drug delivery

In comparison to other transdermal & dermal delivery systems, Ethosomal drug delivery has

enhanced permeation of drug through skin.

Delivery of large molecules is possible.

It contains non‐toxic raw material in formulation.

High patient compliance: ‐ The ethosomal drug is administrated in semisolid form (gel or

cream) hence producing high patient compliance.

The Ethosomal system is passive, non‐invasive and is available for immediate

commercialization.

Ethosomal drug delivery system can be applied widely in Pharmaceutical, Veterinary,

Cosmetic fields.

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Simple method for drug delivery in comparison to Iontophoresis and Phonophoresis and

other complicated methods.

Method of preparation

There are two methods which can be used for the formulation and preparation of ethosomes.

Both of the methods are very simple and convenient and do not involve any sophisticated

instrument or complicated process. Ethosomes can be formulated by following two methods.

a) Hot method: In this method disperse phospholipid in water by heating in a water bath at

400 ⁰C until a colloidal solution is obtained. In a separate vessel properly mix ethanol and

propylene glycol and heat upto 400c. Add the organic phase into the aqueous phase. Dissolve

the drug in water or ethanol depending on its solubility . The vesicle size of ethosomal

formulation can be decreased to the desire extent using probe sonication or extrusion method.

b) Cold method: This is the most common and widely used method for the ethosomal

preparation. Dissolve phospholipid, drug and other lipid materials in ethanol in a covered

vessel at room temperature with vigorous stirring. Add propylene glycol or other polyol

during stirring. Heat the mixture upto 300 ⁰C in a water bath. Heat the water upto 300c in a

separate vessel and add to the mixture and then stir it for 5 min in a covered vessel. The

vesicle size of ethosomal formulation can be decreased to desire extend using sonicatio or

extrusion method. Finally, the formulation should be properly stored under refrigeration [15].

5. Niosomes: Niosomes are formations of vesicles by hydrating mixture of cholesterol and

nonionic surfactants.

Fig 7: Niosome

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Advantages of Niosomes

The application of vesicular (lipid vesicles and non-ionic surfactant vesicles) systems in

cosmetics and for therapeutic purpose may offer several advantages.

Niosomal dispersion in an aqueous phase can be emulsified in a nonaqueous phase to

regulate the delivery

rate of drug and administer normal vesicle in external non-aqueous phase.

They are osmotically active and stable, as well as they increase the stability of entrapped

drug.

Handling and storage of surfactants requires no special conditions.

They improve oral bioavailability of poorly absorbed drugs and enhance skin penetration

of drugs.

They can be made to reach the site of action by oral, parenteral route. [16]

Method of preparation of Niosomes

Niosomes can be prepared by a number of methods [17] [18]

which are as follows

Ether Injection Method

Hand Shaking Method (Thin Film Hydration Technique)

Reverse Phase Evaporation Technique

Multilamellar vesicles (mlv)

Transmembrane pH gradient Drug Uptake Process.

CONCLUSION

For the last few years, advanced drug delivery systems have been investigated to overcome

the limitation of the conventional systems. Herbal drugs have enormous therapeutic potential

which should be explored through some value added drug delivery systems. Lipid solubility

and molecular size are the major limiting factors for drug molecules to pass the biological

membrane to be absorbed systematically following oral or topical administration. Several

plant extracts and phytomolecules, despite having excellent bio-activity in-vitro actions

demonstrate less or no in-vivo actions due to their poor lipid solubility. The NDDS

innovation is especially relevant to those who are sensitive to drug toxicity and it helps to

avoid gastrointestinal disorders. It produces minimal drug level in the blood serum, with

chances of toxicity. This is a significant advantage for patient who needs medication several

times a day. Administration of NSAIDs by novel drug delivery system at a site of tissue

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injury delays the onset and lowers the intensity of pain at lower doses than usually

administered orally.

REFERENCES

[1] Costas Kaparissides, Sofia Alexandridou, Katerina Kotti and Sotira Chaitidou. Recent

Advances in Novel Drug Delivery Systems, Submitted: July 1st, 2005, Posted: March

25th, 2006.

[2] N. B Khavare et al. A Review on key parameters and components in Designing of

Osmotic Controlled Oral Drug Delivery Systems; Indian Journal of Novel Drug

delivery 2(4), Oct-Dec, 2010, 122-131.

[3] Dimitrios Misirlis. Development of a novel drug delivery System based on polymeric,

thermoresponsive, Hydrogel nanoparticles.Thesis no 3362; 2005.

[4] Nidhi Mishra, Narayan P Yadav, Phyto-vesicles: conduit between conventional and

novel drug delivery system, Asian Pacific Journal of Tropical Biomedicine (2012) S

1728-S1734.

[5] Priyanka R. Kulkarni, Jaydeep D Yadav, Liposomes: A novel drug delivery system

International Journal of Current Pharmaceutical Research ISSN- 0975-7066 Vol 3,

Issue 2, 2011.

[6] Akbarzadeh et al, Liposome: Classification, Preparation, and Applications. Nano-scale

Research Letters 2013, 8:102.

[7] J.S. Dua1, Prof. A. C. Rana, Dr. A. K. Bhandari , Liposome: Methods of preparation

and applications, International Journal of Pharmaceutical Studies and Research. E-ISSN

2229-4619.

[8] Threveen Challa, Vinay Vynala, Krishna Vamshi Allam, Colon specific drug delivery

systems: A review on primary and novel approaches. International Journal of

Pharmaceutical Sciences Review and Research,Volume 7, Issue 2, March – April 2011;

Article-031.

[9] Solanki U et al., Overview of cubosomes: A nano particle, International Journal of

Pharmacy and Integrated Life Sciences Vol: 1(5) April 2013.

[10] Madhurilatha et al. Overview of cubosomes: a nano particle, IJRPC 2011, 1(3).

[11] Deepak Prashar et al, Cubosomes: A Sustained Drug Delivery Carrier. Asian J. Res.

Pharm. Sci. 1(3): July-Sept. 2011; Page 59-62.

[12] A. D. Dinsmore, Colloidosomes: Selectively Permeable Capsules Composed of

Colloidal Particles; Science vol 298,1 November 2002.

www.wjpps.com

3461


[13] R. Parthibarajan et al, Colloidosomes drug delivery: a review, IJPBS, Volume 1, Issue

3, July-Sept 2011, 183-197.

[14] Akiladevi et al., Ethosomes a Noninvasive approach for transdermal drug delivery, Int J

Curr Pharm Res, Vol 2, Issue 4, 14.

[15] Vimal Kumar Shahwal, Ethosomes: an overview, International Journal of Biomedical

and Advance Research (2011) 02(05).

[16] Madhav et al, Niosomes: a novel drug delivery system, IJRPC 2011, 1(3).

[17] Kshitij B. Makeshwar, Niosome: a Novel Drug Delivery System, Asian J. Pharm. Res.

2013; Vol. 3: Issue 1, Pg 16-20.

[18] V. Lokeswara Babu et al, Niosomes – vesicular drug delivery system, Int J Pharm

2013; 3(1): 180-185

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