Microemulsion in nanoparticles synthesis

Colloids, Surfactant and Microemulsion.

Preparation and, Application of Microemulsion in nanoparticles synthesis and their use in delivery of Hydrophobes and encapsulation.

Objective of Study

Microemulsions are known systems having a high solubilization capacity for the oil. In past years ME shown immense promise in various technical and industrial fields.

1. Drug or similar deliveries.

2. Synthesis of nanostructures,

Purpose 1:

The first purpose of this Proposal is to develop Microemulsion formulation for enhancing the delivery of poor water soluble substances. A non toxic surfactant/polymer-based Microemulsion formulation can be developed for delivery of such species. Phase behavior and solubilization capacity of the Microemulsion system can be determined. A single isotropic region, which was considered to be a Bicontinuous Microemulsion. The Microemulsion system will also be investigated in terms of other characteristics, such as interfacial tension, viscosity, pH, refractive index, diffusion, and bioavailability.

Another characteristic of the MEs are their ability to emulsify spontaneously when diluted with water/oil. This phenomenon of spontaneous emulsification gives rise of uniform size of droplets which varies from nano to sub micron range. Beauty of this type of emulsions is their high stability as compared to conventional emulsions. Also these emulsions are formed at much lower cost of energy (Molecular level disturbances due to sudden change in interfacial tension) as compared to the conventional emulsions. Spontaneously formed emulsions can be used to deliver water insoluble materials. Further these kinetically more stable emulsions can be made thermodynamically stable by choosing a proper electrolyte or surfactant.

Both “Single phase ME” and emulsion formed from via spontaneous emulsification has immense potential in drug and similar kind of deliveries.

Pharmaceutical Applications

Advantages of Microemulsion Based Systems

Microemulsions exhibit several advantages as a drug delivery system:

1. Microemulsions are thermodynamically stable system and the stability allows self-emulsification of the system whose properties are not dependent on the process followed.

2. Microemulsions act as super solvents of drug. They can solubilize hydrophilic and lipophilic drugs including drugs that are relatively insoluble in both aqueous and hydrophobic solvents. This is due to existence of micro domains of different polarity within the same single-phase solution.

3. The dispersed phase, lipophilic or hydrophilic (oil-in-water, O/W, or water-in-oil, W/O Microemulsions) can behave as a potential reservoir of lipophilic or hydrophilic drugs, respectively. The drug partitions between dispersed and continuous phase, and when the system comes into contact with a semi-permeable membrane, the drug can be transported through the barrier.

4. The mean diameter of droplets in Microemulsions is below 0.22 mm; they can be sterilized by filtration. The small size of droplet in Microemulsions e.g. below 100 nm, yields very large interfacial area, from which the drug can quickly be released into external phase when absorption (in vitro or in vivo) takes place, maintaining the concentration in the external phase close to initial levels.

5. Same Microemulsions can carry both lipophilic and hydrophilic drugs.

6. Because of thermodynamic stability, Microemulsions are easy to prepare and require no significant energy contribution during preparation. Microemulsions have low viscosity compared to other emulsions.

7. The use of Microemulsion as delivery systems can improve the efficacy of a drug, allowing the total dose to be reduced and thus minimizing side effects.

8. The formation of Microemulsion is reversible. They may become unstable at low or high temperature but when the temperature returns to the stability range, the Microemulsion reforms.

Purpose 2:

Another application of MEs includes synthesis of nanoparticles. As we have seen the domain sizes of the MEs are in the nanometer range hence they can be considered as nano-reactors. One of two ME system can be brought into contact to have a reaction inside these nano domains and the particle can be synthesized using a precipitation reaction. This includes example of synthesis of high surface area catalysts.

(Daniel H. M. Buchold and Claus Feldmann, Adv. Funct. Mater. 2008, 18, 1002-1011) etc.

Methodology of study

Approach to form MEs:

A proper and accurate nature of surfactant determines the correct Microemulsion formation, For example Winsor ratio, HLB. Most of them are qualitative. These were reported as a guide. A Most accurate quantitative relation was given by Salager et. al. it is a semi empirical equation known as hydrophilic lipophilic deviation HLD. it is a dimension less number which determines the deviation from the optimum formulation and can be related to partition coefficient of a surfactant in a given conditions. A HLD negative or positive determines affinity of surfactant for water or oil. HLD zero determines the exact balance of affinity of surfactant for oil and water phase. Another guide that can be used qualitatively to determine the Microemulsion condition is phase inversion. For nonionic surfactants temperature is the key field variable how ever since anionic surfactants are less sensitive to temperature, electrolytes cons. Can be taken as a main field variable to obtain a phase inversion. Phase inversion may take place when a w/o emulsion converts to an o/w or vice versa. While going through this change system may attains a condition, when surfactant has equal affinity for oil phase and water phase, which leads to formation of a Microemulsion.

How it will be accomplished:

Microemulsion formation, control of composition, temperature, pH and electrolytes etc.

(A) Ternary (Oil water Surfactant) Phase Behavior Studies.

(B) Scattering Techniques for Microemulsions Characterization.

(C) Nuclear Magnetic Resonance Studies.

(D) Interfacial Tension.

(E) Viscosity Measurements.

(G) Conductance Measurement.

(H) Characterization of Nanostructures

Equipment required (List is not Final)

High ResolutionMicroscope

Conductivity meter

pH meter

High speed temp control Centrifuge

Jacketed water bath

Water bath

Differential and static light scattering Facility

Viscosity meter

High speed video recorder

Electron Microscope ( Not mandatory)

Small Angle Neutron Scattering Instrument Facility

Magnetic stirrers etc.

The Challenges and Un-answered questions:

To date Microemulsions have been shown to be able to protect labile drug, control drug release, increase drug solubility, increase bioavailability and reduce patient variability. How ever making Microemulsion at a very dilute concentration of surfactants is still being explored. Microemulsions can be used to synthesize nanoparticles. But control of the particle size and the rules that governs is still a challenge to face.

Connection with the existing Research at University of Leeds.

The current Research in the field of nano-science carried bout by Prof. Yulong and his Group which includes topics like, interfaces between nano-particle engineering, energy engineering, bioengineering and surface and interfacial chemistry. Specifically Nano-fluids formulation and characterization Nano-based detergent formulation Nanoparticles for stabilizing suspensions and emulsions Microencapsulation using nanoparticles Antimicrobial nano-fluids Antimicrobial nanostructured surfaces Multi-scale modelling of nano-fluids, are very much in lined with the proposed research topic.

A formal interest have already shown to Prof. Yulong regarding this topic through email.

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