INTRODUCTION:

Formulating a poorly water soluble drug has always been a challenging problem confronted by the pharmaceutical scientist. Nano technology can be used to solve the problems associated with these conventional approaches for solubility and bioavailability enhancement. Nano is a Greek word, which means ‘dwarf’.

Nanosuspension technology can also be used for drugs which are insoluble in both water and organic solvents. 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 1um in size. Hydrophobic drugs such as Atrovastatin, Famotidine, Simvastatin, Revaprazan, Aceclofenac, are formulated as Nanosuspension. A pharmaceutical nanosuspension is defined as very finely dispersed solid drug particles in an aqueous vehicle for either oral and topical use or parenteral and pulmonary administration. In nanosuspension technology, the drug is maintained in the required crystalline state with reduced particle size, leading to an increased dissolution rate and therefore improved bioavailability. Bioavailability is defined as the rate and extent to which the active ingredient is absorbed from a drug product and becomes available at the site of action⁽¹⁾. Poorly water soluble drugs are increasingly becoming a problem in terms of obtaining satisfactory dissolution within the gastrointestinal tract that is necessary for good oral bioavailability. The formulation of nano-sized particles can be implemented to all drug compounds belonging to biopharmaceutical classification system BCS classes 2 and 4 to increase their solubility and hence partition into gastrointestinal barrier. Nanosuspension have revealed their potential to tackle the problems associated with the delivery of poorly water- soluble and lipid- soluble drugs, and are unique because of their advantage they confer over other strategies. This review focuses on various aspects of nanosuspension, what are the techniques of formulate the same , advantages, applications, and other aspects which are related to improvement of drugs solubility and bioavailability⁽⁷⁾.

Criteria for selection of Nanosuspension as a dosage form:

· Conventionally the drugs that are insoluble in water but soluble in lipids are formulated as nanosuspension.

· Drugs having log p value very high, high melting point and high dose.

· Drugs having low bioavailability.

The above described requirements have driven the development of nanosuspension technology⁽²⁾.

Advantages of nanosuspensions:

The major advantages of nanosuspension technology are:

· It can be applied for poorly water soluble drugs but which are soluble in lipid to improve their solubility.

· It gives long-term physical stability due to the presence of stabilizers.

· It can be given by various routes.

· It can be provides ease of manufacture and scale-up for large scale production.

· Nanosuspension has low incidence of side effects by the excipients.

· It has higher bioavailability and more consistent dosing in case of ocular administration and inhalation delivery.

· Nanosuspension can be incorporated in various dosage forms like, tablets, pellets, hydrogl , suppositories are suitable for various routes of administration.

· Nanosuspension increases resistance to hydrolysis and oxidation, increased physical stability to settling.

· Drug with higher log p value can be formulated as nanosuspensions to increase the bioavailability of such drugs.

· Improvement of biological performance due to high dissolution rate and saturation solubility of the drugs.

· Reduction in tissue irritation in case of subcutaneous/ intramuscular administration.

· Increase in adhesive nature, thus resulting in enhanced bioavailability.

· Possibility of surface- modification of nanosuspension for site specific delivery.

· Increasing the amorphous fraction in the particles leading to a potential change in the crystalline structure and higher solubility.

· Rapid dissolution and tissue targeting can be achieved by IV route of administration and oral administration provide rapid onset of action by reduced fed/ fasted ratio and improved bioavailability⁽¹⁰⁾.

Disadvantages of nanosuspension:

· Improper dose.

· Uniform and accurate dose cannot be achieved.

· Physical stability, sedimentation and compaction can cause problems.

· It is bulky sufficient care must be taken during handling and transport⁽^9,10).

Method for preparation of Nanosuspension:

Mainly there are two methods for the preparation of nanosuspension. The conventional methods of precipitation are called ‘Bottom up technology’. The ‘Top down Technologies’ are the disintegration methods and are preferred over the precipitation methods. The ‘Top Down Technologies’ include media milling, high pressure homogenization in water, high pressure homogenization in non aqueous media and combination of precipitation and high- pressure homogenization⁽¹⁵⁾.

1. Bottom up technology

^2.Top down technology⁽¹²⁾

There are various methods for preparation of nanosuspension,

1. Media milling (Nanocrystal)

2. Homogenization in non- aqueous media (Nanopure)

3. Combined precipitation and homogenization (Nanoedge)

4. Hydrosol method

5. Supercritical fluid method

6. Dry co- grinding

7. Emulsion as template

8. Emulsifying – solvent evaporation technique

9. Nanojet technology

10. Homogenization in water (Disso Cubes)⁽⁸⁾.

1. Media milling

This method was first developed and reported by Liversidge (1992). Nanosuspension are produced by using high- shear media mills or pearl mills. The mills consists of a milling chamber, milling shaft and a recirculation chamber. An aqueous suspension of the drug is then fed into the mill containing small grinding balls/ pearls. As these balls rotate at a very high shear rate under controlled temperature at least 2-7 days, they fly through the grinding jar interior and impact against the sample on the opposite grinding jar wall. The combined forces of friction and impact produce a high degree of particle size reduction. The milling medium is composed of glass, zirconium oxide or highly cross linked polystyrene resin. Planetary ball mill is one example of the equipment that can be used to achieve a grind size below 0.1 um.

Advantages:

· Media milling is applicable to the drugs that are poorly soluble in both aqueous and organic media.

· Simple technique.

· Nanosize distribution of final nanosized products.

· Very dilute as well as highly concentrated nanosuspensions can be prepared by handling 1 mg/ml to 400 mg/ml drug quantity⁽^16,17).

Disadvantages:

· The media milling technique is time consuming.

· Scale up is not easy due to mill size and weight.

· Potential growth of germs in the water phase when milling for a long time.

· Duration of the process not being very production friendly.

· Some fractions of particles are in the micrometer range.

· Potential erosion from the milling material leading to product contamination.

2. Homogenization in non aqueous media (Nanopure):

Nanopure is the technology in which suspension is homogenized in water- free media or water mixtures like PEG 400, PEG 1000 etc. in the Dissocubes technology, the cavitation is the determining factor of the process. But, in contrast to water, oils and oily fatty acids have very low vapour pressure and a high boiling point. Hence, the drop of static pressure will not be sufficient enough to initiative cavitation. The results obtained were comparable to Dissocubes and hence can be used effectively for thermo labile substances at milder conditions. Patents covering disintegration of polymeric material by high- pressure homogenization mention that higher temperatures of about 80 promoted disintegration, which cannot be used for thermo labile compounds. In nanopure technology, the drug suspension in the non- aqueous media were homogenized at 0 or even below the freezing point and hence are called “ deep- freeze” homogenization. The results obtained were comparable to Dissocubes and hence can be used effectively for thermo labile substances at milder conditions⁽⁵⁾.

Advantages:

· Narrow size distribution of the nanoparticulate drug present in the final product.

· Ease of scale- up and little batch-to-batch variation.

· Drugs that are poorly soluble in both aqueous and organic media can be easily formulated into nanosuspension.

· Flexibility in handling the drug quantity, ranging from 1 to 400 mg/ ml, thus enabling formulation of very dilute as well as highly concentrated nanosuspensions.

· Allows aseptic production of nanosuspension for parenteral administration.

Disadvantages:

· Prerequisite of suspension formation using high- speed mixers before subjecting it to homogenization.

· Prerequisite of micronized drug particles⁽^116,18).

3. Combined precipitation and homogenization (Nanoedge):

Using a precipitation technique, the drug is dissolved in an organic solvent and this solution is mixed with a miscible anti- solvent. In water – solvent mixture the solubility is low and the drug precipitates. Mixing precesses vary considerably. Precipitation has also been coupled with high shear processing. The basic principles of nanoedge are the same as that of precipitation and homogenization. A combination of these techniques results in smaller particle size and better stability in a shorter time. The major drawback of the precipitation technique, such as crystal growth and long- term stability, can be resolved using the nanoedge technology. Rapid addition of a drug solution to an anti- solvent leads to sudden super- saturation of the mixed solution, and generation of fine crystalline or amorphous solids. In this technique, the precipitated suspension is further homogenized, leading to reduction in particle size and avoiding crystal growth. Precipitation is performed in water using water- miscible solvents such as methanol, ethanol and isopropanol. It is desirable to remove those solvents completely, although they can be tolerated to a certain extent in the formulation. For an effective production of nanosuspension using the nanoedge technology, an evaporation step can be included to provide a solvent- free modified starting material followed by high- pressure homogenization.

4. Hydrosol method:

This is similar to the emulsification- solvent evaporation method. The only difference between the two methods is that the drug solvent is miscible with the drug antisolvent. Higher shear force prevents crystal growth and Ostwald ripening and ensures that the precipitates remain smaller in size⁽⁵⁾.

5. Supercritical fluid method:

Supercritical fluid technology can be used to produce nanoparticles from drug solutions. The various methods attempted are rapid expansion of supercritical solution process, supercritical anti- solvent process precipitation with compressed anti- solvent process. The particle size reduction was achieved more by the solubilization and nanosizing technologies through the super critical fluid process. Super critical fluids are noncondensable dense fluids whose temperature and pressure are greater than its critical temperature and critical pressure. The low solubility of poorly water- soluble drugs and surfactants in supercritical CO2 and the high pressure required for these processes restrict the utility of this technology in the pharmaceutical industry.

6. Dry co- grinding:

Dry co- grinding can be carried out easily and economically and can be conducted without organic solvents. Successful work in preparing stable nanosuspension using dry- grinding of poorly soluble drugs with soluble polymers and copolymers after dispersing in a liquid media has been reported. Many soluble polymers and copolymers such as PVP, polyethylene glycol, hydroxyl propyl methylcellulose and cyclo- dextrin derivatives have been used. Physicochemical properties and dissolution of poorly soluble water soluble drugs were improved by co- grinding because of an improvement in the surface polarity and transformation from a crystalline to an amorphous drug. The co- grinding technique can reduce particles to the submicron level and a stable amorphous solid can be obtained.

Advantages:

· Easy process and no organic solvent required.

· Nanosized distribution of final nanosized products.

· Require short grinding time.

Disadvantages:

· Generation of residue of milling media.

7. Emulsion as template:

The use of emulsion as templates is applicable for those drugs that are soluble in either volatile organic solvent or partially water- miscible solvent. Such solvents can be used as the dispersed phase of the emulsion. There are two ways of fabricating drug nanosuspensions by the emulsification method. In the first method, the organic solvent or mixture of solvents loaded with the drug is dispersed in the aqueous phase containing suitable surfactants to form an emulsion. The organic phase is then evaporated under reduced pressure so that the drug particles precipitate instantaneously to form a nanosuspensionm stabilized by surfactants. Since one particle is formed in each emulsion droplet, it is possible to control the particle size of the nanosuspension by controlling the size of the emulsion droplet. Optimizing the surfactant composition increases the intake of organic phase and ultimately the drug loading in the emulsion. Originally, organic solvents such as methylene chloride and chloroform were used. The emulsion is formed by the conventional method and the drug nanosuspension is obtained by just diluting the emulsion. Dilution of the emulsion with water causes complete diffusion of the internal phase into the external phase, leading to instantaneous formation of nanosuspension.

Advantages:

· Ease scale- up if formulation is optimized properly.

· Particle size can easily be controlled by controlling the size of the emulsion droplet.

· Use of specialized equipment is not necessary.

Disadvantages:

· Safety concerns because of the use of hazardous solvents in the process.

· Need for di- ultrafiltration of the drug nanosuspension, which may render the process costly.

· Drugs that are poorly soluble in both aqueous and organic media cannot be formulated by this technique.

8. Emulsification- solvent evaporation technique:

This technique involves preparing a solution of drug followed by its emulsification in another liquid that is a non- solvent for the drug. Evaporation of the solvent leads to precipitation of the drug.

9. Nanojet technology:

This technique, called opposite stream or nanojet technology, uses a chamber where a stream of suspension is divided into two or more parts, which colloid with each other at high pressure. The high shear force produced during the process results in particle size reduction. The major disadvantage of this technique is the high number of passes through the microfluidizer and the product obtained contains a relatively larger fraction of microparticles.

10. Homogenization in water (Disso cubes):

This technology was developed by R.H.Muller using a piston- gap type high pressure homogenizer in 1999. In this method, the suspension containing a drug and surfactant is forced under pressure through a nanosized aperture valve of a high pressure homogenizer. This technique has been used to prepare nanosuspension of many poorly water soluble drugs. This method is based on the cavitation principle. The dispersion present in 3 cm diameter cylinder is suddenly passed through a very narrow gap of 25 um. According to Bernoullis law the flow volume of liquid in a closed system per cross section is constant. It leads to increase in dynamic pressure and decrease of static pressure below the boiling of water at room temperature due to reduction in diameter from 3 cm to 25 um. Then water starts boiling at room temperature and forms gas bubbles, which implode when the suspension leaves the gap and normal air pressure is reached. The particles cavitation forces are sufficiently high to convert the drug micro particles into nanoparticles.

Advantages:

· It is applicable to the drugs that are poorly soluble in both aqueous and organic media.

· It does not cause the erosion of processed materials.

Disadvantages:

· High cost instruments are required that increases the cost of dosage form.

· Pre- processing like micronization of drug is required⁽^1,3,6,8,10).

Formulation of Nanosuspension:

Excipients	Function	Example
Stabilizers	Prevent ostwalds ripening and agglomeration of nanosuspension, provide steric or ionic barrier.	Poloxomers, Povidones, Cellulosics, Polysorbate, Lacithins
Co- surfactants	Influence phase behavior when micro emulaions are used to formulate nanosuspensions.	Bile salts, Ethanol, Isopropanol, Transcutol, Glycofurol
Organic solvent	Pharmaceutically acceptable less hazardous solvent for preparation of formulation.	Methanol, Ethanol, Chloroform, Ethyl acetate, Triacetin, Benzyl alcohol.
Pre-servatives	Having very low concentration for the stability of the formulation for longer period of time.	Benzalkonium chloride, phenyl ethyl alcohol.
Other additives	According to the requirement of the route of administration or the properties of the drug moiety.	Buffers, Salts, Polyols, Osmogens, Cryoprotectants.

Nanosuspension formulation requires stabilizer, surfactant, solvents, preservatives and other excipients used for the preparation⁽¹⁾.

Stabilizer:

The main function of a stabilizer is to wet the drug particles thoroughly, and to prevent ostwals’s ripening and agglomeration of nanosuspensions in order to yield a physically stable formulation by providing steric or ionic barrier. The type and amount of stabilizer has a pronounced effect on the physical stability and in vivo behavior of nanosuspension. Stabilizers that have been used so far are poloxomers, polysorbate, cellulosics, povidone and lecithins⁽^19,23).

Organic solvent:

These are generally used in preparation of nanosuspension if emulsion or microemulsions technologies are used as template for this. These solvents are very hazardous in physiologic and environmental means but still some less hazardous water miscible solvents like methanol, ethanol, chloroform, isopropanol, and partially water miscible solvents ethyl acetate, butyl lactate, ethyl formate, triacetine, propylene carbonate, benzyl alcohol are used over the dichloromethane.

Co- surfactants:

The choice of co- surfactant is critical when using micro emulsion to formulate nanosuspension. Since co- surfactants can greatly influence phase behavior, the effect of co- surfactant on uptake of the internal phase for selected micro emulsion composition and on drug loading should be investigated. Various solubilizers like, Transcutol, glycofurol, ethanol and isopropanil can be safely used as co- surfactants in the formulation of microemulaions.

Preservatives:

Most of the nanosuspensions require preservative to protect the formulation for longer period of time. Preservatives used in formulation having very lowest concentration but helps to maintain the stability throughout the use of the product. Most of the times used preservative in the formulations is Benzalkonium chloride otherwise the combination of benzalkonium chloride and phenyl ethyl alcohol can be preferred.

Other additives:

Nanosuspensions may contain other excipients depends on either the route of administration or physicochemical properties of candidate drug but some additives such as buffers, salts, polyols, osmogent and cryoprotectants are normally used⁽⁹⁾.

Characterization of Nanosuspension:

Evaluation of nanosuspension can be classified according to their in- vivo and in- vitro performance ;

In vitro evaluation

1. Color, odor, taste

2. Particle size distribution

3. Zeta potential

4. Crystal morphology

5. Dissolution velocity and saturation solubility

6. Density

7. pH value

8. Droplet size

9. Viscosity measurement

10. Osmolarity

11. Stability of nanosuspension⁽^21,22,23).

1. Color, odor, taste:

These characteristics are especially important in orally administered formulation. Variations in taste, especially of active constituents, can offered be attributed to changes in particle size, crystal habit and subsequent particle dissolution. Changes in color, odor and taste can also indicate chemical instability.

2. Particle size distribution:

The particle size distribution is an important characterization parameter as it influence the saturation solubility, dissolution velocity, physical stability as well as biological performance of nanosuspensions. This can be determined by photon correlation spectroscopy, laser diffraction and coulter counter multisizer. The photon correlation spectroscopy method can measure particles in the range of 3 nm to 3 um and the laser diffraction method has a measuring range of 0.05 – 0.80 um. The coulter counter multisizer gives the absolute number of particles, in contrast to the laser diffraction method, which gives only a relative size distribution.

3. Zeta potential:

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

o Ionization of the particle surface or

o Adsorption of ions onto the surface

Zeta potential is the potential at the hydrodynamic shear plane and can be determined from the particle mobility under an applied electric field. The mobility will depend on the effective charge on the surface. Zeta potential is also a function of electrolyte concentration.

4. Crystal morphology:

To characterize the polymorphic charges due to the impact of high pressure homogenization in the crystalline structure of the drug, techniques like x- ray diffraction analysis in combination with different scanning calorimetry or differential thermal analysis can be utilized. Nanosuspension can undergo a change in the crystalline structure, which may be to an amorphous form or to other polymorphic forms because of high pressure homogenization.

5. Dissolution velocity and saturation solubility:

The saturation solubility of the drug in different physiological buffers as well as at different temperatures should be assessed using methods describes in the literature. The investigations of the dissolution velocity of nanosuspensions reflect the advantages that can be achieved over conventional formulations, especially when designing the sustained release forms based on nanoparticulate drugs. The evaluation of saturation solubility and dissolution velocity helps in determining the invitro behavior of the formulation⁽²⁴⁾.

6. Density :

Specific gravity or density of the formulation is an important parameter. A decrease in density often indicates the presence of entrapped air within the structure of the formulation. Density measurements at a given temperature should be made using well mixed, uniform formulation; precision hydrometer facilitate such measurements.

7. pH value:

This value of aqueous formulation should be taken at a given temperature and only after settling equilibrium has been reached, to minimize “pH drift” and electrode surface coating with suspended particles. Electrolyte should not be added to the external phase of the formulation to stabilized the pH.

8. Droplet size:

The droplet size distribution of micro emulsion vesicles can be determined by either light scattering technique or electron microscopy. Dynamic light scattering spectrophotometer which uses a neon laser of wavelength 632 nm.

9. Viscosity measurement:

The viscosity of lipid based formulations of several compositions can be measured at different shear rates at different temperatures using Brookfield type rotary viscometer. The sample room of the instrument must be maintained at 37 by a thermo bath and the samples, for the measurement are to be immersed in it.

10. Osmolarity:

Practically, osmolarity of nanosuspension can be measured by using osmometer⁽^1,10,12).

Stability of nanosuspension:

Stability of nanosuspension depends 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 effect and improving the stability of the nanosuspension by providing a steric or ionic barrier. Typical example of stabilizers used in nanosuspensions are cellulosics, poloxomer, polysorbates, polyoleate, povidones and lecithin etc⁽^25,26).

In vivo evaluation

1. Surface hydrophobicity

2. Adhesion properties

3. Interaction with body proteins

Surface hydrophobicity:

For intravenous injected nanosuspensions, additional parameters need to be determined which affect the in vivo fate of the drug nanoparticles. Surface hydrophobicity is considered as one of the important parameters affecting the in vivo organ distribution after intravenous injection. The surface hydrophobicity determines the interaction with cells prior to phagocytosis and in addition, it is a relevant parameter for the adsorption of plasma proteins the key factor for organ distribution. A suitable technique is hydrophobic interaction chromatography, previously employed to determine surface hydrophobicity of bacteria, and then transferred to the characterization of nanoparticulate drug carrier⁽^3,4).

Applications of nanosuspension:

Nanosuspensions have various pharmaceutical and biopharmaceutical application a few of them highlighted below:

o Formulation the drug as nanosuspensions increases the saturable concentration, dissolution rate as well as bioavailability of the drug.

o Nanosuspensions can prove to be a boon for drugs that exhibit poor solubility in lachrymal fluids. For delivery of such drugs, approaches such as suspensions and ointments have been recommended.

o Bioavailability enhancement: drug with poor solubility or permeability in gastrointestinal tract leads to poor oral bioavailability. Nanosuspension resolves the problem of poor bioavailability by solving the problem of poor solubility, and poor permeability across the membranes. The poor oral bioavailability of the drug may be due to poor solubility, poor permeability or poor stability in the gastrointestinal tract. Bioavailability of poorly soluble oleanolic acid, a hepato- protective agent, was improved using a nanosuspension formulation. This was due to the lyophilized nanosuspension powder when compared with the dissolution from a coarse powder.

o These nanosuspensions are having application in different routes of administrations like oral, parenteral, topic, ophthalmic, mucoadhesive, pulmonary and targeted drug delivery⁽^4,6).

1. Oral route of administration:

The oral route is the preferred route for drug delivery because of its numerous well- known advantages. The efficacy or performance of the orally administered drug generally depends on its solubility and absorption through the gastrointestinal tract. Hence, a drug candidate that exhibits poor aqueous solubility and / or dissolution rate limited absorption is believed to possess slow and/ or highly variable oral bioavailability. Nanosizing of drugs can lead to a dramatic increase in their oral absorption and subsequent bioavailability. Improved bioavailability can be explained by the adhesiveness of drug nanoparticles to the mucosa, the increased saturation solubility leading to an increased concentration gradient between gastrointestinal tract lumen and blood as well as the increased dissolution velocity of the drug. The aqueous nanosuspension can be used directly in the granulation process or as a wetting agent for preparing the extrusion mass pellets. A similar process has been reported for incorporating solid lipid nanoparticles into pellets. Granulates can also be produced by spray drying of nanosuspensions.

2. Parenteral route of administration:

Nanosuspensions can be used to transform poorly soluble non- injectable drugs into a formulation suitable for intravenous administration. Although the production of nanosuspension for parenteral use is critical, current developments in this technology have proved its utility as injectable formulations. The methods used for preparation of nanosuspension are now precisely controlled, and are able to produce uniform particles with better control over maximum particle size. Various research reports are available which emphasize the applicability of nanosuspensions for parenteral administration.

3. Ophthalmic route of administration:

Nanosuspensions could prove to be vital for drugs that exhibit poor solubility in lachrymal fluids. Suspensions offer advantages such as prolonged residence time in a cul- de- sac, which is desirable for most ocular diseases for effective treatment and avoidance of high tonicity created by water soluble drugs. Their actual performance depends in the intrinsic solubility of the drug in lachrymal fluids. Thus the intrinsic dissolution rate of the drug in lachrymal fluids controls its release and ocular bioavailability. The bio- erodible as well as water soluble/ permeable polymers possessing ocular tolerability could be used to sustain the release of the medication.

4. Pulmonary route of administration:

Aqueous nanosuspensions can be nebulized using mechanical or ultrasonic nebulizer for lung delivery. Basically the nanosuspensions can be used in all nebulizers. The dispersions can be relatively high concentrated. Due to presence of many small particles instead of a few large microparticles, all aerosol droplet are likely to contain drug nanoparticles. Budesonide, a poorly water soluble corticosteroid, has been successfully prepared as a nanosuspension for pulmony delivery. A good relationship was obtained between increasing the drug concentration in the formulation and the number of micrograms of drug delivered per actuation. In addition, buparvaquone nanosuspensions were formulated for treatment of lung infections by using nebulizers.

5. Topical route of administration:

The nanocrystalline form possesses increased saturation solubility resulting in enhanced diffusion of the drug into the skin. Nanocrystals also exhibit various properties such as increased penetration into a membrane, enhanced permeation and bioadhesiveness which could be very useful for dermal application.

6. Mucoadhesive drug delivery:

Nanosuspension containing drug nanoparticles orally diffuse into the liquid media and rapidly encounter the mucosal surface. The particles are immobilized at the intestinal surface by an adhesion mechanism referred to as “bioadhesion.” The direct contact of the particles with the intestinal cells through a bioadhesive phase is the first step before particle absorption. The adhesiveness of the nanosuspensions not only helps to improve bioavailability but also improves targeting of the parasites persisting in the GIT.

7. Target drug delivery:

The uptake of drug nanoparticles depends in their particle size. By changing the surface properties of the nanoparticles, their in vivo behavior can be altered and can be used as targeted delivery system. The phagocytotic uptake of nanocrystals can be a avoided by preparing stealth nanocrystals or by preparing smart crystals that is drug particles below particle size of 100 nm, which can be used as a targeted drug delivery system^(22,24).

Marketed products based on nanosuspension:

All the products based on nanosuspension have been approved by the FDA from the year 2000 on.

Route of administration	Marketed products
Oral	Itraconazole, Amphotericin B, Acyclovir, Nebivolol HCL, Albendazole Nanosuspension
Pulmonary	Budesonide, Fluticasone and Budesonide Nanosuspension
Parenteral	Risperidone, p- terphenyl derivative, Acetaminophen Nanosuspension
Topical	Curcumin, Silver Sufacetamide Nanosuspension
Ocular	Triancinolone acetonide, Sulfacetamide loaded Eudragit R 100, Moxifloxacin loaded polymer

Future scope:

Nanosuspension technology is novel and unique technology to overcome the drug problems such poor bioavailability that are related with the delivery of hydrophobic drugs, including those that are poorly soluble in aqueous as well as organic media. Production methods like media milling and high- pressure homogenization have been successfully employed for large scale production of nanosuspensions. This technology can be combined with traditional dosage forms: tablets, capsules, pellets, and can be used for parenteral products. To take advantage of nanosuspension drug delivery, simple formation technologies and variety applications, nanosuspensions will continue to be of interest as oral formulations and non- oral administration develop in the future. In consideration to data available nanosuspensions can be considered as renaissance in formulation technologies for coming years⁽¹⁾.

CONCLUSION:

Nanosuspension solves the problems like poor bioavailability of hydrophobic drugs and drugs which are poorly soluble in aqueous and organic solutions. Production techniques such as media milling and high- pressure homogenization used for large scale production of nanosuspensions. Nanosuspensions can be administered orally, pulmonary, ocular, parenteral and topical route of administration. Since this technique is simple and precise, having less requirement of excipients, increased dissolution velocity and saturation solubility many poor bioavailability drugs are formulated in nanosuspension form.

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Received on 01.12.2015 Accepted on 29.12.2015

Asian J. Pharm. Res. 5(4): October- December, 2015; Page 186-194

DOI: 10.5958/2231-5691.2015.00029.5