INTRODUCTION:

Nanoemulsions/ Submicron emulsions (SMEs)/Mini-emulsions are thermodynamically stable, transparent or translucent dispersions of oil and water protected by an interfacial layer of surfactant and cosmetic molecules of less than 100 nm globular scale. Nanoemulsions are commonly used to supply vaccines, medications associated with DNA, medicines, cosmetics, and topical preparations. These are delivered via various routes, such as oral, pulmonary, intranasal and transdermal, etc.¹ Classified as multi-phase colloidal dispersion, nanoemulsions are distinguished by their stability and clarity.The dispersed process typically consists of small particles or droplets, and the interfacial stress between oil and water is very low Spontaneously and easily form nanoemulsions, and sometimes usually without high-energy inputs.

A cosurfactant or cosolvent is used in many cases as opposed to the surfactant, the oil process and the water cycle.^2-5 Nanoemulsions have benefits as they have relatively high kinetic stability for many years. They can be made from deformable droplets into monodisperse structures that are highly uniform. The small droplets and thermal excitation action make them stable against creaming and prevent them from coalescing due to high surface load.⁶ Because of their long life and clear appearance, they are ideal for cosmetics, personal care products and coatings.Their small size makes them perfect for drug delivery systems as they can pass into target sites via lipid membranes as well as oil recovery where they have high infectivity and penetration without filtration into the reservoir rocks.⁷ Nanoemulsions are also an interesting form of dispersion to be studied. These have special optical and rheological properties compared to microscale emulsions.

Types of nanoemulsions^8-9

Three types of nanoemulsions are most likely to form based on their composition:

· Oil in water Nanoemulsions in which oil droplets are dispersed in a continuous aqueous phase;

· Water in oil Nanoemulsions in which water droplets are dispersed in a continuous oil phase;

· Bi-continuous nanoemulsions in which oil and water microdomains are interdispersed in witnesses.

The interface is stabilized in all three types of nanoemulsions by an acceptable mixture of surfactants and/or co-surfactants. The key difference between emulsions and nanoemulsions is that while the former may have excellent kinetic stability, they are essentially thermodynamically unstable and will ultimately be separated. Another important difference is their appearance; emulsions are cloudy while nanoemulsions are either transparent or translucent. In addition, there are distinct differences in their preparation process, as emulsions involve a high input of energy during nanoemulsions.

Advantages of nanoemulsion over other dosage forms¹⁰

1. Increase the rate of absorption.

2. Eliminates the difference of absorption.

3. Helps solubilize lipophilic drugs.

4. Provides aqueous delivery type for water-insoluble medicines.

5. Increases in bioavailability.

6. Different routes, such as topical, oral and intravenous, may be used to deliver the product.

7. Rapid and successful penetration of drug mood.

8. Helpful in masking the taste.

9. Provides protection from hydrolysis and oxidation as an oil-phase product that is not subjected to water and air attack in O / W nanoemulsion.

10. The liquid delivery form improves patient compliance.

11. That's right. Less consumption of energy

12. Nanoemulsions are a thermodynamically stable system and the stability helps to self-emulsify the system, the properties of which are not dependent with the next phase

13. The same nanoemulsions can hold both lipophilic and hydrophilic drugs.

14. Using nanoemulsion as delivery systems will improve the effectiveness of a medication, reduce the overall dosage and thus minimize side effects.

Disadvantages of nanoemulsion based systems ¹¹

1. Use of a large concentration of surfactant and co-surfactant to stabilize the nanodroplets.

2. Small ability for high-melting substances solubilization.

3. The surfactant must be non-toxic in order to use drug products.

4. Nanoemulsion stability is influenced by environmental parameters such as temperature and pH, which change as nanoemulsion is obtained by patients.

Components of Nanoemulsion:

Oils:

The selection of a proper oily step is very important because it influences the selection of other nanoemulsion ingredients, usually in the case of o/w nanoemulsions. Nanoemulsions were typically chosen to shape the oil with the greatest solubilizing potential as an oily step. This makes the maximum load of drugs for nanoemulsion.¹² Naturally occurring oils and fats contain a mixture of triglycerides of various fatty acid chain lengths and degrees of unsaturation. Triglycerides are classified as short (< 5 carbons), medium (6-12 carbons) or long chain (> 12 carbons) and may be synthetically hydrogenated to reduce the degree of unsaturation resulting in resistance to oxidative degradation.Oily phase selection is also a compromise between its ability to solubilize drugs and its ability to promote the production of desirable nanoemulsion properties.¹³Some suitable oil phases include Captex 355, Myritol 318, IPM, modified vegetable oils, digestible or non-digestible oils and fats such as olive oil, palm oil, corn oil, oleic acid, sesame oil, soybean oil, hydrogenated soybean oil, peanut oil and beeswax.¹⁴

Surfactants:

The surfactant should be able to microemulsify the oily process and should also have a high solubilizing ability for the hydrophobic chemical compounds. To formulate nanoemulsion, the choice of surfactant is important Surfactants with an HLB value < 10 are hydrophobic (such as sorbitan monoesters) and form w/o nanoemulsion where high HLB (> 10) surfactants such as polysorbate 80 are hydrophilic and type o / w nanoemulsion.¹⁵ The hydrophobic center enables the binding of drugs and thus maximizes its solubility.When the oil content is high, the surfactant concentrates on the emulsion-forming oil/water interface, where the internal oil phase is solubilized in the drug. Low oil content, minute oil-trapped surfactant globules, known as nanoemulsions, are produced.¹⁶ The surfactant used in the formation of nanoemulsions may be ionic or non-ionic, but due to toxicological effects, ionic surfactants are not preferred Different surfactants, such as lecithins, poloxamers and polysorbate 80, are mostly used.

Co-surfactants:

In addition, surfactant alone can not sufficiently minimize the interfacial tension between oil and water to create a nanoemulsion requiring the addition of a co-surfactant to provide near zero surface tension.Co-surfactants penetrate the monolayer of the surfactant providing additional fluidity to the interfacial surface, distracting the phases of liquid crystalline formation when the film is too rigid.¹² Typically a very low HLB co-surfactant is used with a high HLB surfactant to modify the overall HLB of the system Unlike surfactant, the co-surfactant may not be able to form independently self-associated structures such as micelles.

Ideally, hydrophilic co-surfactants are intermediate-chain alcohols such as hexanol, pentanol and octanol, known to reduce the oil/water interface and allow spontaneous nanoemulsion to form.¹⁴ Finest processing such as ethanol, glycerol, propylene glycol (PG), polyethylene glycol (PEG) are ideal for oral delivery and allow large amounts of either the hydrophilic surfactant or the drug in the lipid base to be dissolvedby co-solvency and by the the dielectric constant of water to make the atmosphere more hydrophobic.¹⁸

Aqueous Phase:

The droplet size and stability of the Aqueous Phase Nanoemulsion is affected by the nature of the aqueous phase. Therefore, due importance should be provided when designing the nanoemulsion, pH and ionic content of the aqueous phase. There have been various pH ranges in the physiological system from pH 1.2 (stomach pH) to 7.4 and higher (blood and intestine pH). Electrolytes, such as droplet size and physical stability, are well known to influence the characteristics of nanoemulsion.

Therefore, it is advisable to evaluate the nanoemulsion and the characteristics of the resulting nanoemulsion in aqueous phases with varying pH and electrolyte concentrations (depending on the application type). Ringer's solution, simulated gastric fluid (pH 1.2), simulated intestinal fluid (pH 6.8) and phosphate buffered saline can be used as an aqueous phase to evaluate the spontaneous nano emulsification of the self-nano drug delivery system.These studies show that the pH of the aqueous phase can have a major impact on the phase behavior of this system, particularly when a pH-dependent drug is loaded into the system.¹⁹

Techniques of Preparation of Nanoemulsions^20-21:

The particle size range of nanoemulsions is very small; the high-pressure equipment can be used to manufacture them most effectively. The most commonly used methods of nanoemulsion processing are "high-pressure homogenization" and "microfluidization," which are used on a laboratory and industrial scale. Certain methods such as "Ultrasonification" and "In-situ emulsification" are also ideal for the preparation of nanoemulsion.

1. High-pressure homogenization:

The preparation of nanoemulsions requires high-pressure homogenization. To produce extremely small particle size (up to 1 nm) nanoemulsions, this technique uses a high-pressure homogenizer / piston homogenizer. The dispersion of two liquids (oily phase and aqueous phase) is achieved by pushing their mixture through a very high pressure small inlet orifice (500 to 5000 psi), which exposes the fluid to intense friction and hydraulic shear resulting in extremely fine particles of emulsion. The formed particles show a fluid lipophilic center separated from the surrounding aqueous phase by a monomolecular layer of phospholipids. This system has high efficiency, with the only drawback being high energy consumption and increased emulsion temperature during processing.

Advantages

· Small batch-to-batch variation and simple scale-up

· Narrow product delivery nanoparticulate.

· The product's value is flexible

· Effective use of thermolabile materials

2. Microfluidization²²:

microfluidization is a mixing procedure that involves a microfluidizer. This system uses a high-pressure positive displacement pump (500 to 20000psi) that moves the fluid through the contact chamber, consisting of small channels called microchannels. The liquid flows through the microchannels into the impingement area, resulting in very small submicron scale particles. To produce a coarse emulsion in an inline homogenizer, the two solutions (aqueous phase and oily phase) are combined and processed together. The coarse emulsion is in a microfluidizer for further processing of a stable nanoemulsion.

The coarse emulsion is repeatedly passed through the interaction chamber microfluidizer until it reaches the desired particle size. The bulk emulsion is then circulated through a filter under nitrogen to remove large droplets that contribute to a uniform nanoemulsion

3. Ultrasonication²³:

The preparation of nanoemulsion is reported in several research papers with the goal of minimizing droplet size using ultrasonic sound frequency. Another approach is to use a constant sonotrode amplitude that exceeds the ambient value at system pressures. It is well known that increasing external pressure increases the cavitation threshold within an ultrasonic field thereby reducing the source of bubbles. However, increasing external pressure often increases the pressure to collapse of cavitation bubbles. It means that the collapse of the bubbles will become greater and more violent when cavitation occurs than when the pressure is in the atmosphere. Since cavitation is the most important power dissipation mechanism in a low-frequency ultrasonic system, these changes in navigational strength can be directly related to changes in power density. A water jacket is also used by the device to control the optimal temperature point.

4. Phase inversion method²⁴:

fine dispersion is obtained by chemical energy as a result of phase transitions produced by the emulsification pathway. The phase transition is generated by varying the composition of the emulsion and holding the temperature constant, or vice versa. Shinoda et al first performed the phase inversion temperature. It was concluded that the increase in temperature results in chemical changes of polyoxyethelene surfactants by degrading the polymer chain with the temperature.

5. Spontaneous emulsification²⁵:

This includes three main steps: i. Preparation of homogenous organic solution consisting of oil and lipophilic surfactant in liquid miscible solvent and hydrophilic surfactant. ii.

The organic phase was injected under magnetic stirring in the aqueous phase, forming the emulsion of o / w. iii. The water-miscible solvent was extracted by evaporation under reduced pressure.

6. Solvent Evaporation Technique²⁶:

This technique involves the preparation of a pharmaceutical solution with its emulsification into another non-solvent medicinal substance. Evaporation of the solution contributes to precipitation of the material. Through creating high shear forces with a high speed stirrer, it is possible to control the growth of crystals and the aggregation of particles.

Characterization of Nanoemulsion:

1. Zeta potential:

Zeta potential is measured by an instrument called Zeta PALS. It is used in nanoemulsion to calculate the load on the droplet surface. Do not only emulsifiers serve as a mechanical barrier, but also by generating surface charges. Zeta potential among approaching oil droplets can produce repulsive electrical forces, and this hinders coalescence. The more negative the zeta potential, the higher the net droplet charge and the more stable the emulsion. A high degree of physical stability is usually demonstrated by zeta potential values below-30 mV. Malvern Zetasizer is based on the dispersion of dynamic light and measures the potential of Zeta.

2. Polydispersity:

The ratio of standard deviation to mean droplet size is polydispersity, thereby implying the uniformity of droplet size within the formulation. The higher the polydispersity in the formulation the lower the uniformity of the droplet size. Malvern Zetasizer is based on dynamic light dispersion and polydispersity measurements.²⁷

3. Particle size analysis:

Dynamic light scattering (DLS) method is generally used to measure particle size and its distribution in the case of nanoemulsion.²⁸

4. Percent Drug Loading:

Pre-weighted nanoemulsion is extracted by dissolving into an appropriate solvent of 25ml, extract is extracted from spectrophotometric / H.P.LC analysis. Against the standard drug solution. By reverse phase HPLC method, the drug content is determined using various columns of appropriate porosity.²⁹

5. Transmission Electron Microscopy (TEM): Nanoemulsion morphology and structure can be analyzed using electron microscopy (TEM) transmission.

6. In-vitro drug release: Nanoemulsion-containing drug studies in vitro release may be investigated using semi-permeable membrane used in a dissolution apparatus. Instead of the basket, a glass cylindrical tube (2,5 cm in diameter and 6 cm in length) should be attached and covered tightly with the semi-permeable membrane. Drug-loaded nanoemulsion is placed on the semi-permeable membrane surface in the cylindrical tube. The cylindrical tube should dip into a 100 ml buffer that keeps the pH to allow sink conditions to be established and permanent solubilization to be maintained. The analysis of release can be conducted for 24 hours at 32̊ C. The stirring shaft will spin at a rate of 100 r.p.m. At fixed time intervals (1, 2, 4, 6, 8, 12, 20, 24 hrs.) one-milliliter aliquots of the release medium are collected and diluted, processed for examination and replaced by the same volume of the buffer solution in order to maintain a steady size. UV spectrometer³⁰ can be used to measure the absorption of the collected samples.

Applications of nanoemulsions^31-36

Parenteral delivery:

Nanoemulsion is an advantage for intravenous administration due to the strict requirement of this route of administration, particularly the need for a formulation droplet size of less than 1 micrometer. For a variety of purposes, such as food, parenteral (or injectable) nanoemulsion administration is used. Fats, carbohydrates, vitamins Fats etc. Natural oils (soybean, sesame and olive) for parenteral feeding nanoemulsions with non-toxic surfactant PluronicF-68. Parenterally, lipidnanoemulsion was thoroughly studied for the delivery of drugs. Nanoemulsion formulations have distinct advantages over macroemulsion systems when distributed parenterally because of the fine particle Nanoemulsion is cleared more slowly than the coarse particle emulsion and therefore have a longer residence period in the body. O/W and W/O Nanoemulsion can be used for parenteral delivery.

Oral delivery:

Nanoemulsion formulations for oral delivery offer several advantages over traditional oral formulation, including increased absorption, improved clinical efficacy and reduced drug toxicity. Consequently, nanoemulsion has been stated to be an ideal supply of drugs such as steroids, hormones, diuretics, and antibiotics. Peptide and protein pharmaceutical drugs are highly potent and special in their physiological functions. When incorporated into oral lipid nanoemulsion, primaquine demonstrated strong antimalarial activity in mice against Plasmodium bergheii infection at a dosage level 25 percent lower than the standard oral dose.

Topical delivery:

For several reasons topical drug administration may have advantages over other approaches, one of which is to prevent the first-pass hepatic metabolism and related toxicity effects of the product. Another is the targeted distribution and targeting of the drug to the affected area of the skin or eyes. The nanoemulsion can achieve a level of topical antimicrobial activity that was previously only achieved by systemic antibiotics. The nanoemulsion has significant fungal activity (e.g. E. coli, S. aureus) (e.g. Candida, Dermatophytes). Ocular delivery Drugs are primarily administered topically for eye disease care.

Ocular delivery:

Drugs are delivered mainly topically for the treatment of eye diseases. For ocular administration, O / W nanoemulsions are investigated to eliminate poorly soluble drugs, improve absorption, and achieve an extended release profile.

In cosmetics:

The esthetic properties of nanoemulsion with droplet sizes below 200 nm, i.e. low viscosity and clear visual features, The high surface area that allows an effective transfer of the active ingredient to the skin makes it particularly desirable to be used in cosmetics. Nanoemulsions are acceptable in cosmetics because there is no intrinsic creaming, sedimentation, flocculation or macroemulsion coalescence observed. The introduction of potentially harmful surfactants can be avoided by using high-energy equipment during manufacturing. Nanogel technology for producing miniemulsion from oil-inwater concentrate, ideal for minimizing transepidermal water loss, enhancing skin safety and penetration of active ingredients. For sun protection, cream moisturization and anti-aging cosmetics, it would be useful. It helps to give a good skin feel to skin care formulations.

Transdermal:

In carrageenan-induced paw edema, transdermal indomethacin, a potent NSAID, was compared to the anti-inflammatory effects of true engineered nanoemulsion formulation in rats. The percentage of inhibition value was important for formed nanoemulsion, so there was great potential for transdermal indomethacin application Nanoemulsions for transdermal delivery of celebrcoxib.

Formulation consisting of 2% celebrcoxib 10% oil phase (Sefsol 218 and Triacetin) 50% surfactant mixture (Tween 80 and Transcutol–P) and 40% liquid.

In biotechnology:

Many enzymatic and biocatalytic reactions are performed in pure organic or aqua-organic media. For these types of reactions, biphasic media are also used. The use of pure apolar media is causing biocatalyst denaturation. It is relatively advantageous to use water-proof media.

CONCLUSION:

The aim of this review is to provide comprehensive information on the various techniques of formulating and characterizing nanoemulsions. Nanoemulsions are thermodynamically stable colloidal dispersion systems consisting of two immiscible liquids combined in a single phase together with emulsifying agents (surfactants and co-surfactants). Although high energy emulsification method is traditionally used for the preparation of nanoemulsion formulation but low emulsion emulsification method now create an attraction now a days due to their wide application and advantages as a formulation and stability aspects. This review gives a detailed idea about a nanoemulsion system. Nanoemulsions are nano-sized emulsions, which are manufactured for improving the delivery of active pharmaceutical ingredients. These are the thermodynamically stable isotropic system in which two immiscible liquids are mixed to form a single phase by means of an emulsifying agent, i.e., surfactant and co-surfactant. The droplet size of nanoemulsion falls typically in the range 20–200 nm. The main difference between emulsion and nanoemulsion lies in the size and shape of particles dispersed in the continuous phase. In this review, the attention is focused to give a basic idea about its formulation, method of preparation, characterization techniques, evaluation parameters, and various applications of nanoemulsion.

ACKNOWLEDGEMENT:

Authors are highly Acknowledge the help of teaching staff of Rajarambapu College of Pharmacy, Kasegaon. For providing necessary information required for review work. Also we are highly Acknowledge the help and guidance of Dr. M. A. Bhutkar.

REFERENCES:

1. Thakur Nishi, GargGarima, Sharma P.K. and Kumar Nitin. Nanoemulsions: A Review on Various Pharmaceutical Applications Global Journal of Pharmacology. 2012;6 (3): 222-225.

2. Theaj Ravi, U Prakash and Thiagaraja P. Irritancy make it a suitable carrier for the Nanoemulsions for drug delivery through different transdermal delivery of the drugs in the routes. Research in Biotechnology.2011; 2(3): 01-13.

3. Sharma N, Bansal M. and Visht S. Nanoemulsion: A new concept of delivery application of nanoemulsion. System.2010;1(2): 2-6.

4. Devarajan V and Ravichandran V: Nanoemulsions: As Modified Drug Delivery Tool. International Journal of Comprehensive Pharmacy. 2011; 4 (01):1-6.

5. Shah P, Bhalodia D. Nanoemulsion: A Pharmaceutical Review. Sys Rev Pharm. 2010; 1(1):24-32.

6. C. Solans, P. Izquierdo, J. Nolla, N. Azemar, “Nanoemulsion,” Curr Opin Colloid Interface Science, Vol 10, 2005, pp 102-112.

7. A. Mandal, A. Bera, K. Ojha, and T. Kumar, “Characterization of Surfactant Stabilized Nanoemulsion and Its Use in Enhanced Oil Recovery”, Society of Petroleum Engineers, 2012.

8. Sole I, Pey CM, Maestro A, Gonzalez C, Porras M, Solans C, et al. Nanoemulsions prepared by phase inversion composition method: preparation variables and scale up. J Colloid Interface Sci 2010; 344:417-23.

9. Ravi TPU, Padma T. Nanoemulsions for drug delivery through different routes. Res Biotechnol 2011; 2:1-13.

10. Trotta, M (1999), “Influence of phase transformation on indomethacin release from microemulsions”, J Control Release, Vol. 60: 399-405.

11. Alvarez-Figueroa, MJ and Blanco-Méndez, J (2001), “Transdermal delivery of methotrexate: iontophoretic delivery from hydrogels and passive delivery from microemulsions”, Int J Pharm, Vol. 215: 57-65.

12. Date AA, Nagarsenker S. Parenteral microemulsion: An overview. Int. J. Pharm. 2008; 355:19-30.

13. Jumaa M, Mueller BW. Formulation and stability of benzodiazepines in a new lipid emulsion formulation. Pharmazie. 2002; 57:740-743.

14. Shaji J, Joshi V. Self-microemulsifying drug delivery system (SMEDDS) for improving bioavailability of hydrophobic drugs and its potential to give sustained release dosage forms. Indian J. Pharm. Educ. 2005; 39(3):130-135.

15. Carey MC, Small DM, Bliss CM. Lipid digestion and absorption. Ann. Rev. Physio. 1983; 45:651-677.

16. Narang AS, Delmarre D, Gao D. Stable drug encapsulation in micelles and microemulsions. Int. J. Pharm. 2007; 345:9-25.

17. Pouton CW, Porter CJH. Formation of lipidbased delivery systems for oral administration: materials, methods and strategies. Adv. Drug Deliv. Rev. 2008; 60:625-37.

18. Gursoy RN, Benita S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed. Pharmacotherap. 2004; 58:173-82.

19. Chime SA, Kenechukwu FC, Attama AA. Nanoemulsions- Advances in formulation, characterization and applications in drug delivery. 2014, 77-111

20. Pershing, LK; Parry, GE and Lambert, LD (1993), “Disparity of in vitro and in vivo oleic acid-enhanced b-estradiol percutaneous absorption across human skin”, Pharm Res, Vol. 10: 1745- 1750.

21. Tanojo, H; Junginger, HE and Boddé, HE (1997), “In-vivo human skin permeability enhancement by oleic acid: transepidermal water loss and Fourier-transform infrared spectroscopy studies”, J Control Release, Vol. 47: 31-39.

22. Hadgraft, J (2001), “Skin: the final frontier”, Int J Pharm, Vol. 224, 1-18

23. Bhatt P and Madhav S: A Detailed Review on Nanoemulsion Drug Delivery System. International Journal of Pharmaceutical Sciences and Research, 2011; 2(10):2482-2489.

24. Kh. Hussan R: Nanoemulsion as a Novel Transdermal Drug Delivery System. International Journal of Pharmaceutical Sciences and Research, 2011; Vol. 2(8):1938- 1946.

25. Devarajan V and Ravichandran V: Nanoemulsions: As Modified Drug Delivery Tool. International Journal of Comprehensive Pharmacy, 2011, 4 (01):1-6.

26. Shah P, Bhalodia D: Nanoemulsion: A Pharmaceutical Review. Sys Rev Pharm, 2010; 1(1):24-32.

27. Jaiswal M, Dudhe R, Sharma PK. Nanoemulsion: an advanced mode of drug delivery system. Biotech, 2014.

28. Gupta PK, Pandit JK, Kumar A, Swaroop P, Gupta S. Pharmaceutical nanotechnology novel nanoemulsion high energy emulsification preparation, evaluation and application. The Pharma Research. 2010; 3:117-138.

29. Sharma N, Mishra S, Sharma S, Deshpande RD, Sharma RK. Preparation and optimization of nanoemulsion for targeting drug delivery. International Journal of Drug Development and Research. 2013; 5(4):37-48.

30. Ghada HE. Formulation and in-vitro evaluation of nystatin nanoemulsion based gel for topical delivery. Journal of American Science. 2012; 8(12).

31. Thakur A, Walia MK, Kumar SLH. Nanoemulsion in the enhancement of bioavailability of poorly soluble drugs: a review. Int Res J 2013; 4:15-25.

32. Shah P, Bhalodia D, Shelat P. Nanoemulsion a pharmaceutical review. Systemic Rev Pharm 2010; 1:24-32.

33. Singh BP, Kumar B, Jain SK, Shafaat K. Development and characterization of a nanoemulsion gel formulation for transdermal delivery of carvedilol. Int J Drug Dev Res 2012; 4:151-61.

34. Heidi MM, Yun Seok R, Xiao W. Nanomedicine in pulmonary delivery. Int J Nanomed 2009; 4:299-319. 22. Charles L, Attama AA. Current state of nanoemulsions in drug delivery. J Biomat Nanobiotech 2011; 2:626-39.

35. Venkatesan N, Yoshimitsu J, Ito Y, Shibata N, Takada K. Liquid filled nanoparticles as a drug delivery tool for protein therapeutics. Biomaterials 2005; 26:7154–63.

36. Kotta S, Khan AW, Pramod K, Ansari SH, Sharma RK, Ali J. Exploring oral nanoemulsions for bioavailability enhancement of poorly water-soluble drugs. Expert Opinion Drug Delivery 2012; 9: 585–98.

Received on 30.01.2020 Modified on 26.02.2020

Asian J. Res. Pharm. Sci. 2020; 10(2):103-108.

DOI: 10.5958/2231-5659.2020.00020.X