INTRODUCTION

The formulation of nano‐sized particles can be implemented to all drug compounds belonging to biopharmaceutical classification system (BCS) classes II and IV to increase their solubility and hence partition into gastrointestinal barrier. Micronization is used for class II drugs of (BCS), i.e. drugs having a good permeability and poor solubility. There are many conventional methods for increasing the solubility of poorly soluble drugs, which include micronization, solubilisation using co‐solvents, salt form, surfactant dispersions, precipitation technique, and oily solution. Other techniques are like liposomes, emulsions, microemulsion, solid dispersion and inclusion complexation using cyclodextrins show sensible achiever, but they lack in universal applicability to all drugs. These techniques are not applicable for those drugs which are not soluble in aqueous and organic solvents. Nanotechnology can be used to solve the problems associated with these conventional approaches for solubility and bioavailability enhancement. Nanosuspension is favoured for compounds that are insoluble in water (but are soluble in oil) with high log P value, high melting point and high doses. Nanosuspension technology can also be used for drugs which are insoluble in both water and organic solvents.

NANOSUSPENSIONS
Nanosuspensions are colloidal dispersions of nanosized drug particles stabilized by surfactants. They can also be defined as a biphasic system consisting of pure drug particles dispersed in an aqueous vehicle in which the diameter of the suspended particle is less than 1μm in size. Reduction of drug particles to nanometer range leads to an enhanced dissolution rate not only because of increased surface area but also because of saturation solubility. The increase in the saturation solubility and solution velocity of nanoparticle is due to increase of vapour pressure of the particles.

Preparation of nanosuspension

Preparation of nanosuspensions were reported to be a more cost effective and technically more simpler alternative than liposomes and other conventional colloidal drug carriers, particularly for poorly soluble drugs and yield a physically more stable product.

TYPES OF NANOSUSPENSION METHODS

(1) micronization by colloid or jet milling, 2) high pressure homogenization,(3) emulsion and milling techniques

Precipitation:

The most common method of precipitation used is anti solvent addition method in which the drug is dissolved in an organic solvent and this solution is mixed with a miscible antisolvent. Mixing processes vary considerably. Precipitation has also been coupled with high shear processing.

Lipid Emulsion/Microemulsion Template:

Lipid emulsions as templates are applicable for drugs that are soluble in either volatile organic solvents or partially water miscible solvents. In this method the drug will be dissolved in the suitable organic solvent and then emulsified in aqueous phase using suitable surfactants. Then the organic solvent will be slowly evaporated under reduced pressure to form drug particles precipitating in the aqueous phase forming the aqueous suspension of the drug in the required particle size.

High Pressure Homogenization:

It is the most widely used method for the preparation of the nanosuspensions of many poorly water soluble drugs .The principle of this method is based on cavitation in the aqueous phase. The particles cavitations forces are sufficiently high to convert the drug microparticles into nanoparticles. The concern with this method is the need for small sample particles before loading and the fact that many cycles of homogenization are required .

Milling Techniques:

Media milling:

In this technique, the nanosuspensions are produced using high-shear media mills or pearl mills. The media mill consists of a milling chamber, a milling shaft and a recirculation chamber. The drug nanoparticles are obtained by subjecting the drug to media milling. High energy and shear forces generated as a result of impaction of the milling media with the drug provide the necessary energy input to disintegrate the microparticulate drug into nanosized particles. The milling medium is usually composed of glass, zirconium oxide or highly cross-linked polystyrene resin.

Evaluation of Nanosuspensions :

In-Vitro Evaluations:
* Particle size and size distribution
* Particle charge (Zeta Potential)
* Crystalline state and morphology
* Saturation solubility and dissolution velocity
* Stability
* In-vivo evaluation:
* In-Vitro Evaluations:

Particle size and size distribution:

It is the most important parameter in the evaluation of the suspensions as it is having the direct effect on the solubility and dissolution rate and the physical stability of the formulation. The mean particle size and the width of particle size can be determined by Photon Correlation Spectroscopy (PCS) , laser diffraction and coulter current multisizer.

Particle charge (Zeta Potential):

The particle charge is of importance in the study of the stability of the suspensions. Usually the zeta potential of more than ±40mV will be considered to be required for the stabilisation of the dispersions. For electrostatically stabilized nanosuspension a minimum zeta potential of ±30mV is required and in case of combined steric and electrostatic stabilization it should be a minimum of ±20mV of zeta potential is required.

Crystalline Sate and Particle Morphology:

It is of importance as there are chances of the polymorphism during the storage of the nanosuspensions. Hence it is necessary to study the crystal morphology of the drug in suspension. Differential Scanning Calorimetry (DSC) is most commonly used for such studies .

Saturation solubility and Dissolution Velocity:

The main advantage associated with the nanosuspensions is improved saturation solubility as well as dissolution velocity. These are studied in different physiological solutions at different pH. Kelvin equation and the Ostwald-Freundlich equations can explain increase in saturation solubility. Determination of these parameters is useful to assess in vivo performance of the formulation.

Stability of Nanosuspensions:

Stability of the suspensions is dependent on the particle size. As the particle size reduces to the nanosize the surface energy of the particles will be increased and they tend to agglomerate. So stabilizers are used which will decrease the chances of Ostwald ripening and improving the stability of the suspension by providing a steric or ionic barrier.

APPLICATION OF NANOSUSPENSIONS

Bioavailability enhancement
Bioavailability enhancementDrug with poor solubility, poor permeability or poor solubility in gastrointestinal tract will leads to poor oral bioavailability. Nanosuspension resolves the problem of poor bioavailability bysolving the problem of poor solubility, and poor permeability across the membranes.

Ocular administration

For delivery of poorly soluble drug in cul‐de‐sac suspensions and ointments are recommended. Suspensions have advantages of prolonged residual time in cul‐de‐sac and avoidance of higher tonicity produced by water soluble drugs. The ocular bioavailability
of suspensions depends on the dissolution rate of the drug inlachrymal fluid.

Pulmonary administration

Aqueous nanosuspension can be nebulized using mechanical or ultrasonic nebulizer for lung delivery. The nanoparticulate nature of thedrug allows the rapid diffusion and dissolution of the drug at the site of action. At the same time, the increased adhesiveness of the drug to mucosal surfaces offers a prolonged residence time for the drug at the absorption site. This ability of nanosuspensions to offer quick onset of action initially and then controlled release of the active moiety is highly beneficial and is required by most pulmonary diseases.

Targeted drug deliver

Nanosuspensions can also be used as targeted drug delivery. The targeted drug delivery can be designed by incorporating the drug into the mononuclear phagocytic system. Targeted drug delivery can be used for the anti‐mycobacterial, fungal or leishmanial drugs to macrophages if the infectious pathogen is persisting intracellular.

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tripathijay.tripathi6@gmail.com