1AISSMS College of Pharmacy, Pune.
2,3Govindrao Nikam college of Pharmacy sawarde
Nanoparticles: - Targeted drug delivery system is a special form of drug delivery system where the medicament is selectively targeted or delivered only to its site of action or absorption and not to the non- target organs or cells. Nanoparticles were first developed by Birrenbach and Spiser and co-worker Kreuter in the year 1976. (1). Nanoemulsion: - Emulsion is a system containing two immiscible phases and composed of at least three components: water phase, oil phase and surfactant phase. The nature of the surfactant determines the continuous phase (external phase) of the emulsion. (6) Aim: - A Review on Nanoemulsion Based System. Objective: - The main objective of nanoemulsion is particle size reduction for the better absorption of drug. It increases the pharmacokinetic effect of the drug substance. With the help of nanoemulsion the drug will release in controlled manner. Nanoemulsion increases the safety profile of the drug. It helps to reduce the drug dosing and improve the bioavailability of drug. Result And Discussion: Nanoemulsion drug delivery technologies efficiently overcome the low bioavailability disadvantage associated with hydrophobic medicines and other pharmaceutical or chemical components with high first pass metabolism. Researchers have employed high energy technologies to improve the delivery of medications and other pharmacological or chemical components. high energy methods are more expensive than low energy methods, which require less energy and are more efficient. Because high energy methods require low surfactant concentrations. Furthermore, research papers show that a higher percentage of surfactant (much higher than CMC level) is used for the formation of Nanoemulsion, regardless of the route of administration, but there is a lack of toxicological evaluation of the prepared Nanoemulsion, which could be a broad research area in the future. Conclusion: Nanoemulsion formulations have various advantages for pharmacological, biological, or diagnostic agent administration. For more than four decades, NEs have been used as whole parenteral feeding fluids in clinics. Although Nanoemulsion are commonly used to provide aqueous insoluble medications, they have lately gained popularity as colloidal carriers for the targeted delivery of certain anticancer drugs, photosensitizes, neutron capture therapy agents, or diagnostic agents. They can be easily targeted to the tumor location due to their submicron size.
Nanoparticles: - Targeted drug delivery system is a special form of drug delivery system where the medicament is selectively targeted or delivered only to its site of action or absorption and not to the non- target organs or cells. Nanoparticles were first developed by Birrenbach and Spiser and co-worker Kreuter in the year 1976.(1).
Emulsion: - Emulsions are metastable colloidal systems composed of one immiscible liquid dispersed in another. Emulsions are utilised in a variety of products, including paints, medications, cosmetics, food, and for improved oil recovery.(2).
Micro-Emulsion: - Micro-emulsions are liquid combinations of oil, water, and surfactant that are transparent, stable, and isotropic; they typically also contain a co- surfactant.(3). Besides that, micro emulsions have droplet sizes of the dispersed phase ranging from 10nm-100nm.(2).
Table No. 1: Property of Macro-emulsion, Nanoemulsion, Micro-emulsion. (6) (7).
|
Sr. No. |
Property |
Macroemulsion |
Nanoemulsion |
Microemulsion |
|
1 |
Size |
1-100 ?m |
20-500 nm |
10-100 nm |
|
2 |
Shape |
Spherical |
Spherical |
Spherical, Lamellar |
|
3 |
Stability |
Thermodynamically Unstable, Weakly Kinetically Stable. |
Thermodynamically Unstable, Kinetically Stable |
Thermodynamically stable |
|
4 |
Method of Preparation |
High & Low Energy Method. |
High & Low Energy Method. |
Low Energy Method. |
|
5 |
Polydispersity |
Often High (>40%) |
Typically, Low (<10> |
Typically, Low (<10> |
|
6 |
Surface-to mass ratio (m2g -1) |
0.07 – 70 |
70 – 330 |
130 – 1300 |
Nanoemulsion: - Emulsion is a system containing two immiscible phases and composed of at least three components: water phase, oil phase and surfactant phase. The nature of the surfactant determines the continuous phase (external phase) of the emulsion. (6) The thermodynamically stable transparent (translucent) dispersions of oil and water known as nanoemulsions, sub-micron emulsions (SMEs), mini-emulsions, and ultrafine emulsion are held together by an interfacial film of surfactant and co-surfactant molecules with a droplet size of less than 100 nm. The oil/water interfacial tension is extremely low in the dispersed phase, which typically consists of minute particles or droplets with a size range of 5 nm to 200 nm. Nanoemulsions are transparent because the droplet size is less than 25% of the wavelength of visible light. Nanoemulsion can occur quickly and occasionally spontaneously, usually without the use of high energy (7). Such nanoemulsions have been employed with a variety of surfactants with different properties (ionic or non-ionic). Among these, nonionic surfactants (such as sorbitan esters and polysorbates), anionic surfactants (such as potassium laurate and sodium lauryl sulphate), cationic surfactants (such as quaternary ammonium halide), and zwitterions surfactants were the most commonly employed ones (quaternary ammonium halide)(4).
Three types of Nanoemulsions are most likely to be formed depending on the composition:
The O/W nanoemulsions further classified into three types based on the type of surfactants used which are as follows-
Fig No. 1- Water in Oil, Oil in Water and Bi-Continuous.
Fig. No. 2 – Type of Nanoemulsion.
Property: -
ADVANTAGES: -
DISADVANTAGES: -
Limitation: -
Characterization Of Nanoemulsion: -
Review Of Literature: -
This review provides brief information about method of preparation and evaluation of nanoemulsion as drug carriers for improving the delivery of therapeutic agents. several techniques are to be used for preparation of nanoemulsions like microfluidization, high pressure homogenization, low energy emulsification and solvent evaporation method and parameter that are to be used for its characterization like droplet size analysis, viscosity determination, drug content, refractive index, pH, zeta potential, Transmission electron microscopy, thermal stability, release and in vitro skin permeation study.
Nanoemulsions are formulated using two different methods, the persuasion method and the Brute force method. Various characterization techniques for nanoemulsions include determination of entrapment efficiency, particle size as well as characterization through scanning transmission electron microscopy. Nanoemulsions are further evaluated by studying in stability and thermodynamic stability, shelf life, dispersibility, viscosity, pH.
One of the most efficient dispersed nanosystems is nanoemulsion having droplet size ranging to submicron size. Nanoemulsions are thermodynamically stable, clear, isotropic liquid mixtures of oil, water, 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. This system is designed to address some of the problems associated with conventional drug delivery systems such as low bioavailability and noncompliance. Now a day nanoemulsions have attracted great attention in research, dosage form design and pharmacotherapy. The stability of nanoemulsion formulations can be maintained by a surfactant and co-surfactant. This review provides brief information about types, method of preparation, stability, evaluation and application of nanoemulsion.
Nanoemulsions are submicron sized emulsions that are under investigation as drug carriers for improving the delivery of therapeutic agents. These are the thermodynamically stable isotropic system in which two immiscible liquids are mixed to form a single phase by means of appropriate surfactant and cosurfactant. Nanoemulsion droplet sizes fall typically in the range of 20- 200nm and shows narrow size distribution.
Nanoemulsions are kinetically stable liquid-in-liquid dispersions with droplet sizes on the order of 100 nm. Their small size leads to useful properties such as high surface area per unit volume, robust stability, optically transparent appearance. Additionally, they serve as model systems to understand nanoscale colloidal dispersions. High and low energy methods are used to prepare nanoemulsions, including high pressure homogenization, ultrasonication, phase inversion temperature and emulsion inversion point, as well as recently developed approaches such as bubble bursting method applications.
The design of effective formulations for drugs has long beena major challenge, because drug efficacy can be severelylimited by instability or poor solubility in the vehicle. One of the most promising technologies is the nanoemulsion drugdelivery system, which is being applied to enhance the solu-bility and bioavailability of lipophilic drugs. Interest in Lipid Based Drug Delivery (LBDD) is relatively recent and relates to the developments in the past 10 to 15 years.
Aim & Objective
Aim: - A Review on Nanoemulsion Based System.
Objective: -
Need For Developing Nanoemulsion: -
Plan Of Work: -
Actual Of Work
Component Of Nanoemulsion: -
Main three components of Nanoemulsions are as follows: (10)
1.Oil
2.Surfactant/Co-surfactant
3.Aqueous phase.
1)Oil: - The choice of a suitable oily phase is critical because it determines the choice of additional nanoemulsion ingredients, particularly in the case of O/W nanoemulsions. Typically, the oil with the greatest solubilizing potential for the selected drug candidate is chosen as an oily phase for the formulation of nanoemulsions. This contributes to the highest drug loading in the nanoemulsions. (8). After water, the oil phase is the second most significant vehicle due to its ability to solubilize lipophilic drug molecules and increase absorption through the body's lipid barrier. Because of its unique ability to penetrate cell walls, oil is extremely effective for lipophilic active medication delivery. (11)
|
Sr. No. |
Oil Type |
Example |
|
1 |
Fatty acid esters |
ethyl or methyl esters of lauric, myristic ,Oleic acid. |
|
2 |
Saturated fatty acids. |
Lauric, capric acid, myristic. |
|
3 |
Unsaturated fatty acids. |
linoleic acid. linolenic acid, Oleic acid |
Table no. 3: Examples of Surfactant
|
Sr. No. |
Types Of Surfactant |
Example |
|
1 |
Cationic surfactants |
Amines and quaternary ammonium compounds such as Cetyl trimethyl ammonium bromide. |
|
2 |
Anionic surfactants |
They contain carboxylate groups. Soaps, sulfonates, divalent ions etc. |
|
3 |
Nonionic surfactants |
Fatty alcohols, glycerol esters, fatty acid esters etc. |
Table no. 4: Examples of Co-Surfactant.
|
Sr. No. |
Types Of Co-Surfactants |
Example |
|
1 |
Short chain alcohols. |
ethanol to butanol |
|
2 |
Medium chain alcohols. |
acids or amines |
|
3 |
Short chain glycols |
propylene glycol |
Table No. 5: List Of Oils Used In Nanoemulsions. (6)
|
Chemical Name |
Name |
Manufacture |
|
Captex 8000 |
Glyceryl Tricaprylate (Tricaprylin) |
Abitec |
|
Witepso |
90:10 % w/ w c12 Glyceride tri: diesters |
Sasol pharmaceutical excipient |
|
Captex 200 |
Dicaprate Glycol Propylene Dicaprylatel |
Abitec |
|
Isopropyl myristate |
Myristic acid isopropyl ester |
Fluka |
|
Myritol 318 |
c8/c10 triglycerides |
Russia |
|
Captex 355 |
Caprate /Glyceryl Tricaorylate |
Abitec |
Techniques Of Preparation Of Nanoemulsion:
Nanoemulsions have very small particle sizes and are best manufactured with high- pressure equipment. The most frequent procedures for creating nanoemulsions are 'High pressure homogenization' which are employed both in the laboratory and on a large scale.
Nanoemulsions are frequently created using high energy technologies. High mechanical energy is utilized to create strong disruptive forces that break up big droplets into nano- sized droplets and produce high kinetic energy nanoemulsions. High energy technologies also give controls for emulsion stability, rheology, and colour. The following methods are associated with high energy methods: (14).
Micro-Fluidization: This method used a micro fluidizer, which is a device that uses a high pressure positive displacement pump (500-20 000 psi) to push the product out through the interaction chamber, which is made up of stainless steel micro channels on the impingement area, resulting in the formation of very small particles in the sub-micron range. The mixture is passed through the microfluidizer several times until the desired particle size is attained. The resulting product is also filtered to separate smaller droplets from bigger ones and to obtain a homogeneous nanoemulsion. (4)
Fig. No.4: Micro-Fluidization (16)
Ultrasonication: The creation of Nanoemulsion is described in several research publications that aim to use ultrasonic sound frequency to reduce droplet size. At system pressures above the ambient value, another alternative is to employ a constant amplitude sonotrode. It is commonly understood that increasing the external pressure raises the cavitation threshold within an ultrasonic field, resulting in fewer bubbles. Increasing the external pressure, on the other hand, raises the collapse pressure of cavitation bubbles. This means that when cavitation occurs, the collapse of the bubbles becomes stronger and more violent than when the pressure is at atmospheric settings Because cavitation is the primary mechanism of power dissipation in a low frequency ultrasonic system. (4) (17).
Fig. No.5: Ultrasonication (16)
High-Shear Stirring Using a Rotor: - The mixing intensity of high shear stirring can reduce the internal phase droplet size, but preparing an emulsion with average droplet size less than 200 - 300nm is difficult. When a viscous phase, such as high viscosity oil, is introduced into the system, the efficacy of high shear stirring decreases, resulting in the creation of droplets in the micro range. Phase inversion is a low energy emulsification technology that produces a small droplet size range of less than 50nm (2) (18).
Fig. No.6: High-Shear Stirring Using a Rotor (16)
ii)Phase inversion composition (PIC):- At a fixed temperature, the PIC technique is based on a change in emulsion mixture phase (o/w to w/o or vice versa) produced by a change in emulsion mixture composition. Pouring the component (water or oil) over a mixture of the other two components (oil-surfactant or water-surfactant, respectively). Slow water addition, for example, transforms w/o micro-emulsions to o/w nanoemulsions (20).
b) Catastrophic Phase Inversion: -
i)Emulsion inversion phase (EIP): - The emulsion inversion point (EIP) method of emulsification is a low-energy and spontaneous emulsification technique. At constant temperature, it results in the intrinsic properties of thermodynamically stable microemulsions or liquid crystals being diverted to be nano-structured by progressive dilution with water or oil, respectively, to create thermodynamically unstable but kinetically stable direct or inverse nanoemulsions. A minor adjustment to the water or oil percentage (21)
2)Self-Nanoemulsion Method: - The self-emulsification approach produces nanoemulsions without affecting the surfactant's spontaneous curvature. Surfactant and/or co-solvent molecules diffuse rapidly from the dispersed phase to the continuous phase, causing turbulence and the formation of nano-sized emulsion droplets. The spontaneous emulsification method is another name for the self- emulsification process. (15).
3)Solvent Evaporation Technique: - In this procedure, a drug solution is created and emulsified into another liquid (a non-solvent for the drug), and then the solvent is evaporated, resulting in drug precipitation. A high-speed stirrer can be used to control crystal formation and particle aggregation. The solvent evaporation approach is quite similar to the hydrogel method. The main difference between this approach and solvent evaporation is that the drug solution is miscible with the drug antisolvent in this situation. (4) (20).
Evalution Test:-
Application: - (32) (33) (34).
1)Parenteral Delivery: Nanoemulsion are advantages for intravenous administration, due to the strict requirement of this route of administration, particularly the necessity for the formulation droplet size lower than 1 micrometer. Parenteral (or Injectable) administration of nanoemulsion is employed for a variety of purposes, namely nutrition eg. Fats, Carbohydrates, Vitamins etc.
2)Oral Delivery: Nanoemulsion formulations offer the several benefits over conventional oral formulation for oral administration including increased absorption, improved clinical potency and decreased drug toxicity. Therefore, Nanoemulsion have been reported to be ideal delivery of drugs such as steroids, hormones, diuretic and antibiotics. Pharmaceutical drugs of peptides and proteins are highly potent and specific in their physiological functions.
3)Pesticide Formulations Pesticide:- nanoemulsion formulations are formulations in which active chemicals used in treating or preventing the crops from any disease which affects agricultural yield have been incorporated into the nanoemulsion system. These types of pesticides have been categorized based on their target organisms.
4)Topical Delivery: Topical administration of drugs can have advantages over other methods for several reasons, one of which is the avoidance of hepatic first pass metabolism of the drug and related toxicity effects. Another is the direct delivery and targetability of the drug to affected area of the skin or eyes. The nanoemulsion can achieve a level of topical antimicrobial activity that has only been previously achieved by systemic antibiotics. The nanoemulsion has broad spectrum activity against bacteria( e.g. E.coli, S. aureus) fungi (e.g. Candida, Dermatophytes).
5)In Biotechnology: Many enzymatic and biocatalytic reactions are conducted in pure organic or aqua-organic media. Biphasic media are also used for these types of reactions. The use of pure apolar media causes the denaturation of biocatalysts. The use of water-proof media is relatively advantageous.
RESULT AND DISSCUSION
Nanoemulsion drug delivery technologies efficiently overcome the low bioavailability disadvantage associated with hydrophobic medicines and other pharmaceutical or chemical components with high first pass metabolism. Researchers have employed high energy technologies to improve the delivery of medications and other pharmacological or chemical components. high energy methods are more expensive than low energy methods, which require less energy and are more efficient. Because high energy methods require low surfactant concentrations. . Furthermore, research papers show that a higher percentage of surfactant (much higher than CMC level) is used for the formation of Nanoemulsion, regardless of the route of administration, but there is a lack of toxicological evaluation of the prepared Nanoemulsion, which could be a broad research area in the future.
CONCLUSION
Nanoemulsion formulations have various advantages for pharmacological, biological, or diagnostic agent administration. For more than four decades, NEs have been used as whole parenteral feeding fluids in clinics. Although nanoemulsions are commonly used to provide aqueous insoluble medications, they have lately gained popularity as colloidal carriers for the targeted delivery of certain anticancer drugs, photosensitizes, neutron capture therapy agents, or diagnostic agents. They can be easily targeted to the tumor location due to their submicron size.
REFERENCES
Mitali Gandhi, Nemade Lalita S.*, Musale Yogesh, A Review on Nanoemulsion Based System, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 1, 1073-1085. https://doi.org/10.5281/zenodo.14643293
10.5281/zenodo.14643293
