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NANOEMULSION

ABDUL MUHEEMM.Pharm, IInd sem.,Department of PharmaceuticsFaculty of Pharmacy,Jamia Hamdard

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Content Definition Introduction Colloidal systems Formulation additives Commercial NEs Formulations Advantages Methods of preparation Techniques of preparation

High -pressure homogenization Microfluidization Phase inversion temperature technique Titration method

Characterisation of microemulsion Applications of nanoemulsion conclusion

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Abbreviations

NE- nanoemulsion SME-sub-micron emulsion o/w- oil in water w/o- water in oil PCMX –parachlorometaxylenol TEWL- trans epidermal water loss

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Definition

Nanoemulsions can be defined as oil-in-water (o/w) emulsions with mean droplet diameters ranging from 50 to 1000 nm.

Synonyms: sub-micron emulsion and mini-emulsion.

Usually SMEs contain 10 to 20 per cent oil stabilized with 0.5 to 2 per cent egg or soyabean lecithin.

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Introduction NEs are a group of dispersed particles used

for pharmaceutical and biomedical aids and vehicles that show great promise for the future of cosmetics, diagnostics, drug therapies, and biotechnologies

Due to their small droplet size NEs possess stability against sedimentation or creaming with Ostwald ripening forming the main mechanism of NE breakdown.

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• Internal structures depend on relative component amounts, concentrations and other characteristics.

• The relative oil and water domains that form in nanoemulsion systems are usually so small (about 10-20 nm or less in diameter) that they do not scatter light.

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Nanoemulsion: Lipid monolayer enclosing a liquid lipid core.

Liposome: Lipid bilayer enclosing an aqueous core.

8MJayne Lawrence and Warankanga Warisnoicharoen, Recent Advances in Microemulsions as Drug Delivery Vehicles (p-125),

Nanoparticle as Drug Carriers, 2006 by Imperial College Press

Nanoemulsion versus a Microemulsion

Microemulsion Nanoemulsion

•Thermodynamically stable. •Kinetically stable

•Comparatively long term stability •Do not possess long-term stability

•Higher surfactant concentration •Requires a lower surfactant concentration for its formation

•Less expensive then nanoemulsion

•Nanoemulsions are generally expensive

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Nanoemulsions are transparent and slightly opalescent.

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Formulation additives

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A Typical Formulation

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Advantages NEs have a much higher surface area and free

energy than macro emulsions that make them an effective transport system.

NEs do not show the problems of inherent creaming, flocculation, coalescence, and sedimentation, which are commonly associated with macroemulsions.

NEs can be formulated in variety of formulations such as foams, creams, liquids, and sprays.

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Advantages NEs are non-toxic and non-irritant, hence

can be easily applied to skin and mucous membranes.

Since NEs are formulated with surfactants, which are approved for human consumption (GRAS), they can be taken by enteric route.

NEs do not damage healthy human and animal cells, hence are suitable for human and veterinary therapeutic purposes.

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Protection of drug(s) from the hostile environment of the body

Better profiles of drug absorption

Reduction in dose

Increased bioavailability

Rapid drug release

Small droplet size large interfacial area

Significance of smaller droplet Size.

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Techniques of preparation

a. High -pressure homogenization

b. Micro fluidization

c. Phase inversion temperature technique.

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High -pressure homogenization

This technique makes use of high-pressure homogenizer/piston homogenizer to produce NEs of extremely low particle size (up to 1nm) 

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MICROFLUIDIZATION: It involves the use of device that is micro fluidizer It uses high-pressure positive displacement pump

of (500-20000)psi, which forces the product through the interaction chamber, which consists of small channels called “micro channels”.

The product flows through the micro channels on to an impingement area resulting in very fine particles of submicron range. The two solutions (aq. Phase and oily phase) are combined together and processed to obtain a stable nanoemulsion.

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Microfluidization

www.ttlindia.com/images/microfluidics1.jpg

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Phase Inversion Temperature technique.

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Characterization of Nanoemulsion

transmission electron microscopy, NE droplet size analysis, viscosity determination, refractive index,  in vitro skin permeation studies,

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Characterization of Nanoemulsion

skin irritation test,  in vivo efficacy study, thermodynamic stability studies,

and surface characteristics.

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Thermodynamic Stability Studies

To overcome the problem of metastable formulation

Selected formulations were centrifuged at 3500 rpm for 30 minutes

Heating and cooling cycle Six cycles between refrigerator temperatures of

4°C and 45°C for 48 hours were done Freeze-thaw cycle test done for the formulations

between –21°C and +25°C.

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Droplet Size Analysis

droplet size of the nanoemulsion is determined by photon correlation spectroscopy

The formulation (0.1 mL) is dispersed in 50 mL of water

Gently mix by inverting the flask. Measurement is done using a Zetasizer 1000

HS. Light scattering is monitored at 25°C at a 90°

angle

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Transmission Electron Microscopy The morphology and structure of the

nanoemulsion the nanoemulsion formulation is diluted with

water (1/100). A drop of the diluted nanoemulsion is directly

deposited on the holey film grid and observed after drying 

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Viscosity Determination

The viscosity of the formulations (0.5 g) can be determined without dilution using a Brookfield DV III ultra V6.0 RV cone and plate rheometer at 25 ± 0.5°C.

one software used for the viscosity calculations is Rheocalc V2.6.

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   Applications of Nanoemulsions

Use of nanoemulsions in cosmetics

Antimicrobial nanoemulsions

Prophylactic in bio-terrorism attack

Nanoemulsions as a mucosal vaccines

Nanoemulsion as non-toxic disinfectant cleaner 

 

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   Applications of Nanoemulsions Nanoemulsion in the treatment of

various other disease conditions Nanoemulsion formulations for

improved oral delivery of poorly soluble drugs 

Nanoemulsions as a vehicle for transdermal delivery 

Self-nanoemulsifying drug delivery systems 

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   Applications of Nanoemulsions Nanoemulsions in cell culture technology

Nanoemulsion in cancer therapy and in targeted drug delivery

Solid self-nanoemulsifying delivery systems as a platform technology for formulation of poorly soluble drugs

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Nanoemulsion as non-toxic disinfectant cleaner 

The disinfectant formulation is made up of nanospheres of oil droplets #106 mm that are suspended in water to create a NE requiring only miniscule amounts of the active ingredient, PCMX (parachlorometaxylenol).

The nanospheres carry surface charges that efficiently penetrate the surface charges on microorganisms' membranes-much like breaking through an electric fence.

Rather than "drowning" cells, the formulation allows PCMX to target and penetrate cell walls.

As a result, PCMX is effective at concentration levels 1-2 orders of magnitude lower than those of other disinfectants; hence, there are no toxic effects on humans, animals, or the environment.

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Nanoemulsions as a mucosal vaccines

Used to deliver either recombinant proteins or inactivated organisms to a mucosal surface to produce an immune response.

An influenza vaccine and an HIV vaccine, can proceed to clinical trials.

The NE causes proteins applied to the mucosal surface to be adjunted and it facilitates uptake by antigen-presenting cells.

This results in a significant systemic and mucosal immune response that involves the production of specific IgG and IgA antibody as well as cellular immunity.

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Antimicrobial nanoemulsions The NE has a broad-spectrum activity against

bacteria (e.g. E. coil,  Salmonella, S. aureus), enveloped viruses (e.g. HIV, Herpes simplex), fungi (e.g. Candida, Dermatophytes), and spores (e.g. anthrax).

The NE particles are thermodynamically driven to fuse with lipid-containing organisms.

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Prophylactic in bio-terrorism attack

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Use of nanoemulsions in cosmetics

NEs support the skin penetration of active ingredients and thus increase their concentration in the skin.

Another advantage is the small-sized droplet with its high surface area allowing effective transport of the API to the skin.

Have own bioactive effects. This may reduce the trans-epidermal water loss, indicating that the barrier function of the skin is strengthened.

NEs are acceptable in cosmetics because there are no inherent creaming, sedimentation, flocculation, or coalescence that are observed with macroemulsions.

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Fluorine-containing nanoemulsions for MRI cell tracking

•cells of interest are labeled in culture using a perfluorocarbon nanoemulsion•Labeled cells are introduced into a subject and tracked using 19F MRI or NMR spectroscopy•widely applied to studies of inflammation, cellular regenerative medicine, and immunotherapy. 

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Nanoemulsions as a vehicle for transdermal delivery 

Low systemic absorption Site-specificity and increased drug

levels at injured tissues Reduced toxicity Improved pharmacological activity

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Parenteral Delivery

In order to increase the solubility of the drug, To reduce drug toxicity, To reduce hypersensitivity, To reduce pain upon injection, Formulated as long circulating vehicles, Control the release rate, As drug targeting agents, Alternative formulation to long circulating vesicles, On the basis of their small size avoiding uptake by the RES, Their stability and their ease of preparation.

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How the top 10 big pharmaceutical companies rank in terms of number of nano-related patents.

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Commercial NEs Formulations

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Conclusion NE formulations offer several advantages for the delivery of drugs,

biologicals, or diagnostic agents. Several other products for drug delivery applications such as

Diprivan® (propofol, astra zeneca) and Ropion® (flurbiprofen) have also reached the marketplace.

NEs are chiefly seen as vehicles for administering aqueous insoluble drugs, as colloidal carriers for targeted delivery of various anticancer drugs, photosensitizers, neutron capture therapy agents, or diagnostic agents.

Because of their submicron size, they can be easily targeted to the tumor area.

Research with perflurochemical NEs has shown promising results for the treatment of cancer in conjugation with other treatment modalities and targeted delivery to the neovasculature. It is expected that further research and development work will be carried out in the near future for clinical realization of these targeted delivery vehicles.

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RESEARCH PAPERS

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INTRODUCTION

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MATERIALS

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NANOPHASIC DIAGRAM CONSTRUCTION & OPTIMIZTION OF ULTRA FINE SUPER SNEDDS

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CHARACTERIZATION & OPTIMIZATION OF SNEDDS

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IN VITRO DISSOLUTION/DRUG RELEASE STUDIES

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IN VITRO STUDIES BETWEEN F1 & MARKETED IND CAPSULE IN DISTILLED WATER

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CONCLUSION OF RESEARCH PAPER

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References:

1. Jia Xi, Qi Chang, Chak K. Chan et al, Formulation Development and Bioavailability Evaluation of a Self-Nanoemulsified Drug Delivery System of Oleanolic Acid. AAPS PharmSciTech, Vol. 10, No. 1, March 2009 (# 2009).

2. Nicolas Anton & Thierry F. Nano-emulsions and Micro-emulsions: Clarifications of the CriticalDifferences www.springerlink.com/index/J4880Q76V1374601.pdf.

3. Shah P, Bhalodia D, Shelat P. Nanoemulsion: A pharmaceutical review. Syst Rev Pharm [serial online] 2010 [cited 2011 Mar 16];1:24-32. Available from: http://www.sysrevpharm.org/text.asp?2010/1/1/24/59509

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Thank You