Department of Pharmaceutics. School of Pharmacy, SRTMU, Nanded. (431606)
*Corresponding Author E-mail: ankushdoiphode51@gmail.com
ABSTRACT:
Nanoemulsions are colloidal emulsions made up of two immiscible liquids, one of which is scattered and the other continuous. Nanoemulsions are two types W/O and O/W. Nanoemulsion are size varies from 20 to 200nm. Nanoemulsions are thermodynamically stable. Emulsifiers are stabilised nanoemulsion. There are two types of emulsifiers: one is hydrophilic and the other is lipophilic. Nanoemulsion is widely used in food industry, beverages, agriculture, bio-pharmaceutical, dairy products. Nanoemulsion widely prepared by using high energy or brute force comprising ultra sonication and ultra high pressure homogenizer and low energy or persuasion method compressing both phase inversion composition (PIC) and the phase inversion temperature (PIT). Newly a developed method used as preparation of nanoemulsion bubble bursting, micro- fluidization and evaporative ripening. The aim of review a article focusing on to preparation method characterization application of nanoemulsion.
KEYWORDS: Nanoemulsion, High pressure homogenizer, Surfactant, Co-surfactant, Oil.
INTRODUCTION:
Nanoemulsions are also known as oil in water (O/W) and water in oil (W/O) emulsions, with droplet diameters ranging from 1 to 1000nm and an average of 50 to 500nm. They are also known as submicron or mini emulsions.1st nanoemulsion are prepared in 1940.
Nanoemulsions are three types one is water in oil (W/O) second is oil in water (O/W) third is bi-continuous. Nanoemulsions are cost effective and easy to preparation. Nanoemulsion having long storage stability. Nanoemulison is physical appearance is translucent or transparent liquid. They are kinetically stable and thermodynamically meta stable.1 Nanoemulsion improve solubility in poorly water soluble drug by using different method precipitation, homogenization, spherical crystallization and surface area increases.
Small droplet size nanoemulsion possess instability in phase separation or phase inversion, sediment a particle in bottom and ostawald ripening are important mechanisms of nanoemulsion breaking. Nanoemulsion is controlled and drug delivery and drug targeting.2
1) Nanoemulsion having larger surface area to make effective transport system.
2) Nanoemulsion does not showing problem of the sedimentation coalescence, flocculation.
3) From Nanoemulsion, Various types of formulation prepared like cream, gel, liquid spray, parenteral and topical
4) Nanoemulsions are having smaller particle size so they can easily permit through the stratum cornium of the skin.
5) Surfactant and co-surfactant used in nanoemulsion are biocompatible so they can easily administered orally.3
6) Nanoemulsion does not damage to the skin of human and animals.
7) Increase the bioavailability of poorly water soluble drugs.
8) They are cost effective.4
1) For stabilizing the nanodroplets, It requires a large number of surfactant and co-surfactant.
2) Nanoemulsions are high cost preparation method.
3) High concentrations of emulsifiers are required.
4) Surfactant must be non-toxic for use in pharmaceutical application.5
Oil: Oil is most a important vehicle because it is properties solubilize lipophilic drug to improve absorption lipid bilayer which are present in body. Oil important for lipophilic active drug delivery its unique property to penetrating cell wall. Surfactant the tail group region swelling in oil phase.6
|
Sr. No |
Oil |
Example |
|
1 |
Unsaturated fatty acid |
Lauricacid, Myristic acid, Caporic acid. |
|
2 |
Saturated fatty acid |
Oleic acid, Linoleic acid, |
|
3 |
Fatty acid ester |
Ethyl or methyl ester of stearic acid |
Surfactant:
Surfactant is also called as lowering the interfacial tension of oil and water interface of a nanoemulsion. The preparation of water in oil nanoemulsion surfactant with hydrophilic lipophilic balance values 3-6 are useful where for the formulation of O/W nanoemulsion surfactant along higher hydrophilic lipophilic balance values 8-18 are useful. Surfactant having HLB value more than 20 acts as co-surfactant. surfactanst can be following type:
· Non –ionic Surfactant
· Anionic Surfactant
· Cationic Surfactant
· Zwitter ionic Surfactant:
Ionic surfactants are sensitivity in stability and toxicity concern..Non-ionic they are produced harmless pharmaceutical dosage form.[7].They are the most popular surfactant. Example of non ionic surfactant areas follows:
|
Sr. No |
Surfactant |
Example |
|
1 |
Nonionic surfactant |
Polysorbates-40, 60, Octylphenolethoxylate ortriton 100, Tergitol 15-s-5, Span, Brij. |
|
2 |
Anionic surfactant |
sodium methyl ester sulfonate, poly methyl ester sulfonate, sodium lauryl sulfate, Alpha olefin sulfate |
|
3 |
Cationic surfactant |
Cetyltrimethyle ammonium chloride , octadecyltrimethylammonium chloride. |
Cosurfactant:
Co-surfactant usually used to enhance the oil solubulization capacity of nanoemulsion formulation or to decrease oil and water interfacial tension.cosurfactant that are commonly used including, diethylene glycol monoethyl ether, glycerol, PEG 400,caprylic acid, and ethanol.8
Aqueous phase:
Aqueous phases are important for the preparation of nanoemulsion because they are containing electrolyte, ionic content and PH of aqueous phase important for stability of nanoemulsion The PH of aquous phase increases preparation are breakdown.9
1) High Energy Approach:
Nanoemulsion are most prepared by high pressure homogenization. This method produce particle size 1nm to 500nm.This method oil or aqueous phases mixed together and transferred in small orifice and operating pressure is ranges between100 to 5000PSI. Thise method extremely small droplet size produced. High pressure Homogenization liquid obtained turbulence and transparent.10
Droplet diameter was reduced by decreasing the interfacial tension between oil and water and regulating the dispersed and continuous phases at low viscosity ratios. High viscosity of liquid does not use of high pressure homogenizer.11
High pressure homogenizer efficiently breakdown the particle diameter and increase the surface area. High pressure homogenizer to produce better quality product. High-pressure homogenizer used to preparation lemon balm lantrozole and agricultural pesticides in norcanthrandin.
High pressure Homogenization used for agriculture industry, cosmetic, dairy industry, biopharmaceutical industry. The low particle size obtained by Homogenization 3-12 cycle performed.12
This method the ultrasonication agitation by sound waves 20 KHz frequency breaks coarse droplet into nanoemulsion. Mechanical vibration is generated by the sonotrode, and a significant shock wave is generated when cavitations collapse, causing coarse droplets to break.13
Nanoemulsion prepared by high frequency (mega Hz) without using emulsifier. The device consists of ultrasonication a chamber having an ultra sonication probe. Ultrasonication the probe is developed disruptive force created interfacial waves breaks the coarse emulsion to produce the fine nanoemulsion.11
Ultrasonication method not used for larger scale production they are using small batch production. The piezoelectric crystal a in the sonicator generate a intense pressure wave. Increase the sonication time to increase impute energy to produce higher the number of droplet to decrease particle size.14
3) Microfludizer:
The device contains a high-pressure positive displacement pump (200-20,000 psi) that forces the product through a small channel known as microchenneles in the interaction chamber.15
The macro size emulsion is passed through the microchenneles on to an imparting area to produce very fine particle of submicron range.16
Uniform a particle size of Nanoemulsion produced from the repeated cycle performed by using the Microfludizer.
Microfludization method is very expensive not suitable for large quantity production nanoemulsion.Thise method difficult and not viable.16
Nanoemulsions are obtained as result a of phase transition of low energy approach produced during emulsification process.
This approach uses chemical energy to create a phase shift that occurs through emulsification.. Changes in temperature at constant composition or at constant temperature create an adequate phase transition.17
A example, if a system used to higher temperature to micro emulsion, the hydrophilic- lipophilic deviation(HCD) for optimum near to the center level close to zero.18 The temperature dependant solubility of non ionic surfactants such as polyethooxylated surfactant is used in the phase inversion temperature method to adjust their efficient for water in oil function .It has been noted that when polyethooxylated surfactants are heated, they tend from lipophilic. This process is employed to prepare the temperature for phase inversion. During the oil and water, surfactant combined at ambient temperature phase inversion temperature method. The method involving heating of the composition the difficult to produced nanoemulsion in the thermoliable drug such as terotin peptide.
This method is self Nano-emulsification method. It can be produce Nano emulsion without using heat and solvent at a room temperature.Nanoemulsiom are kinetically stable at Nano size around 50nm range19. When salt is added to an oil–water nanoemulsion containing an ionic emulsifier, the emulsifier’s hydrophilic–lipophilic behavior is altered.. The element charge of the surfactant changes and turn to water in oil emulsion with ionic emulsifier. By diluting with water, high salt can be turned to oil in water. Thise procedure is inexpensive and does not necessitate the use of any special equipment. It’s an organic solvent with excellent thermodynamic stability.
It involves main three steps
1. Formulation of homogenization a mixture of oil and water miscible, solvent and hydrophilic surfactant or lipophilic surfactant.
2. The oil and surfactant mixture was transferred to purified water under the magnetic stirrer the o/w emulsion was formed.
3. By evaporating at reduced pressure, the aqueous phase miscible solvent is removed.20
For the characterization of Nanoemulsion droplet size, viscosity measurement, surface charge, Electrocunductivity measurement, percentage transmission study, Refractive index, PH, Thermodynamics stability, Transmission electron microscopy, Dye test, In Vitro bioavibilty Study shall be performed.
1) Droplet size analysis:
The particle size distribution and analysis of the manufactured nanoemulsion were employed in the Dynamic light scattering device. For nanoemulsion and nanosuspension, particle size distribution is critical.21
2) Viscosity measurement:
Viscosity analysis is common a method used to evaluate response the stability nanoemulsion to stress condition. The viscosity value of prepared formulation measured by plate viscometer (HADV3T Rheometer, Brookfield, UK)at different the share rate.22
3) Surface charge measurement:
Surface charge detected by zeta potential of nanoemulsion. Droplet size measured along the help of mini a electrode.21
4) Zeta potential Measurement:
Measurement carried out using nanoZS apparatus (Malvan instruments) equipped with DTS 1060 cell. After filteration1/10 dilution of nanoemulsion in Nacl 1nM was performed.23
5) Electrocunductivity measurement:
The conductivity nanoemulsion determined by using condoctometer CDM 230.The reading was taken at the frequency of 94 Hz cell constant of 0.11cm. The measurement performed at 25+0.5°C.24
6) Refractive index:
The refractive index to check the transparency of the nanoemulsion formulation. Referactive index performed by instrument a Abbes referactometer at the room temp. The checking refractive index of formulation to compared with a refractive index of water.18
7) pH:
pH is the most important parameter for the nanoemulsion. The excipients used for the formulation decide the final pH of formulation and route of the administration. The change in pH may effect on zeta potential turn can affect on stability of nanoemulsion. The pH of formulation using by the digital pH meter 25.
8) Thermodynamics stability Study:
The different thermodynamics stability study.
a) Heating cooling cycle: are containing the three cycle the temp storage in 4°C to 45°C test not less than 48 hours. The formulations are stable for heating cooling cycle those are transferred to centrifugation test.
b) Centrifugation: The heating cooling cycle the formulation is stable they are centrifugation at 3600rpm for 30min. The formulation does not separation of phase are used for freeze thraw cycle.
c) Freeze thraw cycle: The freeze thraw cycle containing the temp -18°C to 25°C.Three cycle is performed for freeze thraw cycle and time not less than 48hrs.26
9) Transmission electron microscopy:
Transmission electron microscopy was used to get high-resolution images of the dispersed phase. A 1% phosphotungastic acid aqueous solution or a 2% uranyl acetate solution is put onto a 200um mesh size to stain the sample adversely. The material was examined using a pioloform-coated copper grid under transmission electron microscopy micropipppet. Size and size measurement in terms of quality. A digitalimage processing programmer can be used to distributed transmission electron microscopy.27
10) Fourier–transform infrared spectroscopy (FTIR): FTIR using for the understand the comparability between excipients and drug. The nanoemulsion investigated using FTIR absorption spectra recorded used attenuated all reflection with PerkinElmer spectrum 1000 FTIR spectrometer at 63 scans per minute over frequency range 4000-650cm.28
A water soluble dye is soluble in w/o globule water but not in o/w globule water. An oil soluble dye is soluble in the w/o globule’s oil but dispersible in the o/w globule’s oil.
In Vitro release study: It was done with the dialysis membrane bag approach. For 8 hours, the dialysis membrane bag is soaked in the phosphate buffer7.4 dialysis membrane submerge phosphate buffer solution withdraw sample 5 ml from dissolution setup. Regular interval in for 8 hours and replace a equal amount of phosphate buffer and keep the sink condition maintain.29
Application of Nanoemulsion:
1) Oral Delivery: Nanoemulsion formulation for oral administration provide various advantages over conventional oral formulation including enhanced absorption, higher bioavailability and reduced drug toxicity Nanoemulsion have been shown to be effective on the transport of steroid hormone, Antibiotic, diuretic and antimalerial. Antimalerial activity against plasmodium falciparam was observed when it was integrated into an oral lipid nanoemulsion. when compared to the standard oral dose infected mice received a 25% lower dose.30
2) Topical delivery: Topical administration provides a number of advantages over other approaches, one of which is the avoidance of toxicity-causing hepatic first-pass metabolism. The oil phase of the nanoemulsion was oleic acid or glucire 44/14 and it was established using a combination of labrasol (c8 and c10 polyglycoside) as well as the plural oleique as surfactant.31
3) Transdermal delivery: By penetrating the critical cellular reservoir nanosized drug delivery device greatly improved the bioavibilty and solubility of active components. When compared to conventional topical formulation nanoemulsion have been shown to improve Transdermal penetration of numerous drug. There have been numerous formulation using nanoemulsion and micro emulsion delivery, research explored the skein permeation mechanism of a Varity of drugs. Transdermal drug delivery systems to increase bioavibilty of hydrophilic drug like Ripinirole hydrochloride, caffine, glycyrhizine 15
4) Pulmonary drug delivery: It has been reported that cationic micron emulsions can be considered a promising carrier for DNA vaccines to the lungs because they can transfect pulmonary cells, which then induce cross antigen-presenting cells and directly active dendritic cells, resulting in antigenic-specific T-cell stimulation. As a result, submicron emulsion nebulization will be a research field. Transdermal drug to cure diseases of fungal infection, heart attack to formulate nanoemulsion in trandermal patches form.15
5) Cosmetic: When compared to an inert cosmetic, a cosmaceutical is a cosmetic product having an active component that is designed to have a beneficial physiological effect as a result of enhanced pharmacological action. The main advantages of employing nanotechnology in cosmetics are that it improves the stability of numerous substances such as Nanoparticles encapsulated with unsaturated fatty acids, vitamins, or antioxidants increased health. Penetration. So far, the mechanisms underlying enhanced skin penetration by nanoemulsion have been linked to the size range and composition of nanoparticles. The surfactant in the diminish the distinct barrier of the stratum corneum. The cosmeceutical formulation that leads to high penetration the nanoemulsion process is utilized in a variety of cosmetics.33
6) Ophthalmic delivery: Nanoemulsion are uses for a ophthalmic drug transport treating numerous eye ailment like Dry eye syndrome, glucoma. A aggregate of oil in water kind emulsion is being generated generally for improved Lipophilic drug transport to eye. Lipophilic drug is generally having expanded absorptivity as compared to Hydrophilic. The bioavibilty is greater and their affected person compliance is discovered to be higher whilst nanoemulsion are Topical set up into the eye.13
7) Food and Agriculture: Vitamins are encapsulated and efficiently delivered in the bloodstream via the digestive system. Nanoparticles are used in the preparation of food and beverages without changing the qualities or the test. Nanoemulsions have also been utilized to improve the consistency and texture of ice cream. Nanoemulsion with wide application range such as food products like muscle food. Nanoemulsion in muscle food applied to the increase shelf life of muscle food.34.
8) Biotechnology: Many biocatylic and enzymatic reaction is conducted in pure aqueous- organic or organic media. Two phase media used for these type reaction. Many enzymes are including lipase, esterase, dihydrogenase and oxides often function in the cell micro-environments that are hydrophilic nature. Enzyme catalysis in nanoemulsion has been employed for a wide range of reactions including ester, peptide, and sucrose acetyl synthesis, transesterification, different hydrolysis reactions, and steroidal transformation.31
Nanoemulsions are isotropic liquid mixtures of oil, water, surfactant, and co-surfactant that are thermodynamically stable. They are clear in nature and transparent. Nanoemulsions are most useful dosage form controlled and targeted drug delivery. Nanoemulsion increase drug solubility, poorly water soluble drug and increase bioavibilty and protect liable drug and reduce drug toxicity. Now a day nanoemulsion formulation variety of route of administration. Nanoemulsions are widely used for pharmaceutical and agricultural industry. Nanoemulsion having several advantages delivery of drug, biological and diagnostic agent. The nanoemulsion main important application masking disagreeable taste of oily liquid. Now days nanoemulsion used for the targeted drug delivery like anticancer, antiviral, antimalarial drug. By controlling factor such as oil phase, surfactant, co- surfactant, preparation method, process variable and addition of additive stability of formulation enhanced.
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Received on 10.02.2022 Modified on 14.04.2022
Accepted on 27.05.2022 ©Asian Pharma Press All Right Reserved
Asian J. Res. Pharm. Sci. 2022; 12(3):239-244.
DOI: 10.52711/2231-5659.2022.00042