INTRODUCTION:

The formulation parameters such as solubility and stability at ambient temperature are playing a vital role in the development of successful drugs formulation. Among this aqueous solubility became an obstacle for the formulation of new drug molecules. More than 40% of the new drugs are being produced through drug discovery programmes are poorly water‐soluble compound. Formulating a poorly water soluble drug has always been a challenging problem to pharma industry [1, 2]. There are many conventional methods such as micronization, solubilisation using co‐solvents, surfactant dispersions and precipitation technique has been developed for improving solubility of poorly soluble drugs, but these techniques showed limitation to

Received on 26.02.2019 Accepted on 26.04.2019

Asian J. Pharm. Res. 2019; 9(2): 130-138.

DOI: 10.5958/2231-5691.2019.00021.2

the drugs which are not soluble in both aqueous and organic solvents. Nanotechnology has been introduced to solve the problems related with conventional approaches for improving solubility and bioavailability. Nanosuspension technology has been used for drugs which are insoluble in both water and organic solvents [3].

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. The Nanosuspensions can also be lyophilized or spray dried and the nanoparticles of a Nanosuspension can also be incorporated in a solid matrix[4-7]. Nano is a Greek word, which means ‘dwarf’. Nano means it is the factor of 10-9 or one billionth. Some comparisons of nanoscale are given below,

0.1 nm = Diameter of one Hydrogen atom.

2.5 nm = Width of a DNA molecule

1 micron = 1000 nm.

1 nm = 10-9m= 10-7 cm = 10-6 mm.

Micron = 10-6m= 10-4 cm = 10-3mm 4.

For a long duration of time micronization of poorly soluble drugs by colloid mills or jet mills was preferred. The overall particle size distribution ranges from 0.1μm to approximately 25μm, only negligible amount being below 1μm in the nanometer range.

CLASSIFICATION OF SUSPENSION [8]

I. Based On General Classes

o Oral suspension

o Externally applied suspension

o Parenteral suspension

II. Based On Proportion Of Solid Particles

o Dilute suspension (2 to10%w/v solid)

o Concentrated suspension (50%w/v solid)

III. Based On Electrokinetic Nature Of Solid

Particles

o Flocculated suspension

o Deflocculated suspension

IV. Based On Size Of Solid Particles

o Colloidal suspension (< 1 micron)

o Coarse suspension (>1 micron)

o Nano suspension (10 ng)

The nanosuspensions can also be lyophilized or spray dried and the nanoparticles of a nanosuspension can also be incorporated in a solid matrix. Apart from this, it has all other advantages of a liquid dosage form over the solid dosage forms. The present review is focused on various methods of preparing nanosuspensions, critical parameters to be characterized and the application of nanosuspension formulations. Most of the drugs are not soluble in water and they create major problem during formulation they also show poor bioavailability. Reduction in particle size of such drugs enhances the dissolution rate and bioavailability. Nano suspension a promising delivery used to enhance the solubility of hydrophobic drugs. Media milling and high pressure homogenization technique are used commercially to produce nano suspensions. Recently emulsion and micro emulsion as templates are used to produce nano suspension. They are administered by Parenteral, per oral, ocular and pulmonary routes. Now their application also extended to site specific delivery.

This review describes the methods of pharmaceutical production, formulations and pharmaceutical applications in drug delivery as well as the marketed products. Nanosuspensions consist of the pure poorly water-soluble drug without any matrix material suspended in dispersion.

Advantages

 Suspension can improve chemical stability of certain drug.

 Drug in suspension exhibits higher rate of bioavailability than Other dosage forms bioavailability is in following order,

Solution > Suspension > Capsule > Compressed Tablet

 Duration and onset of action can be controlled.

 Suspension can mask the unpleasant/ bitter taste of drug.

Disadvantages

 Physical stability, sedimentation and compaction can causes problems.

 It is bulky sufficient care must be taken during handling and transport.

 Uniform and accurate dose cannot be achieved unless suspension are

 In a proper dose.

Applications

 Suspension is usually applicable for drug which is insoluble or poorly

 soluble.

 To prevent degradation of drug or to improve stability of drug.[9-11]

ORAL SUSPENSIONS

The suspensions contain relatively high amounts of suspended material for oral administration. The vehicle may be syrup, a sorbitol solution, or a gum-thickened, water containing artificial sweetener because in addition to ingredients, safety, taste, and mouth feel are important formulation considerations. In the case of limited shelf life (low chemical stability of the insoluble drug), the dosage form may be prepared as a dry granulation or powder mixture that is reconstituted with water prior to use.

TOPICAL SUSPENSIONS

Historically, the externally applied ‘‘shake lotion’’ is the oldest example of a pharmaceutical suspension. The protective action and cosmetic properties of topical lotions usually require the use of high concentrations of the dispersed phase, often in excess of 20%.

Therefore, topical lotions represent the best example of suspensions that exhibit low settling rates. Various pharmaceutical vehicles have been used in the preparation of topical lotions, including diluted oil-in-water or water-in-oil emulsion bases, determatological pastes, magmas, and clay suspensions. Safety and toxicity are import combination for determatological acceptability. some time, the drug particles settled slowly, forming tightly packed sediment that was almost impossible to resuspend even with vigorous shaking. Primary particles or small aggregates, reaching the bottom of the container during sedimentation (settling), slipped past each other and produced compact layers of solids. The inter particle interaction in such compact sediments is relatively high because the inter particle distances are small, and the weak van der Waals forces of attraction. Such conditions frequently lead to the undersirable phenomenon of ‘‘caking or claying’’ and require extensive agitation for resuspension. The physical instability of these early deflocculated suspensions led to other methods of producing physically stable pharmaceutical suspensions. Deflocculated suspensions are produced by three methods

1) Mutual repulsion to large z-potential.

2) Adsorption of a smaller hydrophilic or lyophilic colloid on larger suspended particles.

3) Steric hindrance due to adsorption of an oriented non-ionic surfactant or polyelectrolyte.

FLOCCULATED SUSPENSIONS

Matthews and Rhodes, Haines and Martin and Ecanow and co-workers are credited with establishing the ‘‘structured particle’’ concept or flocculated pharmaceutical suspension. The following figure explains different term like flocculation, agglomeration, and coagulation.

The term aggregation can apply to all three.

Flocculation refers to the formation of a loose aggregation of discrete particles held together in a network like structure by physical adsorption of macromolecules, bridging during. chemical interaction (precipitation) or when the longer-range van der Waals forces of attraction exceed the shorter-range forces of repulsion. The floccule referred to as a ‘‘stable loc’’ usually contains varying amounts of entrapped liquid medium or vehicle within the network like structure Flocculated pharmaceutical suspensions are prepared using several methods. The choice depends on the properties of the drug and the class of suspension desired. A stable flocculating may also be produced by dispersing insoluble particles in a turbid or hazy vehicle consisting of finely dispersed or emulsified semi polar, liquid droplets, which cause the droplets to be adsorbed on the surface of the insoluble drug particles, resulting in a stable floc. Turbid aqueous vehicles have been prepared by the interaction of non-ionic surfactants and preservatives. The concentration of surfactant and preservative required for haze formation may be reduced by the addition of small amounts of sorbitol to the vehicle. [12-15]

Potential Benefits of Nanosuspension Technology for Poorly Soluble Drugs

 Reduced particle size, increased drug dissolution rate, increased rate and extent of absorption, increased bioavailability of drug, area under plasma versus time curve, onset time, peak drug level, reduced variability, reduced fed/fasted effects.

 Nanosuspensions can be used for compounds that are water insoluble but which are soluble in oil. On the other hand, Nanosuspensions can be used in contrast with lipidic systems, successfully formulate compounds that are insoluble in both water and oils.

 Nanoparticles can adhere to the gastrointestinal mucosa, prolonging the contact time of the drug and thereby enhancing its absorption. Nanosuspension has low incidence of side effects by the excipients.

 Nanosuspensions overcome delivery issues for the compounds by obviating the need to dissolve them, and by maintaining the drug in a preferred crystalline state of size sufficiently small for pharmaceutical acceptability.

 Increased resistance to hydrolysis and oxidation, increased physical stability to settling.

 Reduced administration volumes; essential for intramuscular, subcutaneous, ophthalmic use.

 Finally, Nanosuspensions can provide the passive targeting.[16-19]

METHODS OF PREPARATION OF NANOSUSPENSION

Mainly there are two methods for preparation of Nanosuspensions. The conventional methods of precipitation (Hydrosols) 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 (Nanocrystals), High Pressure Homogenization in water (Dissocubes), High Pressure Homogenization in non aqueous media (Nanopure) and combination of Precipitation and High-Pressure Homogenization (Nanoedege).

1) Bottom-up technology

2) Top-down technology

Bottom-Up Technology

The term “Bottom-up technology” means that one starts from the molecular level, and goes via molecular association to the formation of a solid particle.That means that we are discussing classical precipitation techniques by reducing the solvent quality, for example, by pouring the solvent into a nonsolvent or changing the temperature or a combination of both. Precipitation is a classical technique in pharmaceutical chemistry and technology.

Advantage

1) Use of simple and low cost equipment.

2) Higher saturation solubility is the advantage for precipitation compared to other methods of Nanosuspension preparation.

Disadvantages

1) The drug needs to be soluble in at least one solvent (thus excluding all new drugs that are simultaneously poorly soluble in aqueous and in organic media).

2) The solvent needs to be miscible with at least one nonsolvent.

3) Solvent residues need to be removed, thus increasing production costs.

4) It is an Iittle bit tricky to preserve the particle character (i.e. size, especially the amorphous fraction). In general, it is recommended that a second consecutive process has to be performed for particle preservation that is spray drying or lyophilization.

Top-Down Technology

The top down technologies include

a) Media milling

b) High pressure homogenization

Media Milling

Nanosuspensions are produced by using high-shear media mills or pearl mills. The mill 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, 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 media or balls are made of ceramic-sintered aluminium oxide or zirconium oxide or highly cross-linked polystyrene resin with high abrasion resistance. Planetary ball mills (PM100 and PM200; Retsch GmbH and Co., KG, Haan, Germany) is one example of an equipment that can be used to achieve a grind size below 0.1 μm. A Nanosuspension of Zn-Insulin with a mean particle size of 150 nm was prepared using the wet milling technique. The major drawbacks of this technology include the erosion of balls/pearls that can leave residues as contaminants in the final product, degradation of the thermolabile drugs due to heat generated during the process and presence of relatively high proportions of particles ≥5 μm.[20-22]

Advantages

 Simple technology

 Low-cost process regarding the milling itself

 Large-scale production possible to some extent (batch process).

Disadvantages

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

 Duration of the process not being very production friendly.

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

 Time and costs associated with the separation procedure of the milling material from the drug

nanoparticle suspension, especially when producing parenteral sterile products.

High Pressure Homogenization

Dissocubes Homogenization involves the forcing of the suspension under pressure through a valve having a narrow aperture. Dissocubes was developed by Muller et al. in 1999. In this case, the suspension of the drug is made to pass through a small orifice that result in a reduction of the static pressure below the boiling pressure of water, which leads to boiling of water and formation of gas bubbles. When the suspension leaves the gap and normal air pressure is reached again, the bubbles implode and the surrounding part containing the drug particles rushes to the center and in the process colloids, causing a reduction in the particle size. Most of the cases require multiple passes or cycles through the homogenizer, which depends on the hardness of drug, the desired mean particle size and the required homogeneity. This principle is employed in the APV Gaulin Micron LAB 40 Homogenizer (APV Homogenizer, Lόbeck, Germany) and the NS 1001L-Panda 2K high-pressure homogenizer (Nirosuavi. S.P.A., Parma, Italy).[23-24]

To produce a Nanosuspension with a higher concentration of solids, it is preferred to start homogenization with very fine drug particles, which can be accomplished by pre-milling. The major advantage of high- pressure homogenization over media milling is that it can be used for both diluted as well as concentrated suspensions and also allows aseptic production.[25]

Nanopure

Nanopure is suspensions homogenized in water-free media or water mixtures. 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 initiate cavitation. Patents covering disintegration of polymeric material by high- pressure homogenization mention that higher temperatures of about 800C promoted disintegration, which cannot be used for thermolabile compounds. In nanopure technology, the drug suspensions in the non- aqueous media were homogenized at 00C 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 thermolabile substances at milder conditions.[26-27]

Nanoedge

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. 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 Nanosuspensions using the Nanoedge technology, an evaporation step can be included to provide a solvent-free modified starting material followed by high-pressure homogenization.

Emulsion Diffusion Method

Apart from the use of emulsion as drug delivering vehicle they can also be used as templates to produce Nanosuspension. The use of emulsions as templates is applicable for those drugs that are soluble in either volatile organic solvent or partially water-miscile solvent. Such solvents can be used as the dispersed phase of the emulsion. An organic solvent or mixture of solvents loaded with the drug is dispersed in the aqueous phase containing suitable surfactants with stirring to form an emulsion. The obtained emulsion was further homogenized by high pressure homogenization. After homogenization cycles the emulsion was diluted with

water, homogenized by homogenizer to diffuse the organic solvent and convert the droplets into solid particles. 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 optimizing the surfactant composition increases the intake of organic phase and ultimately the drug loading in the emulsion. Originally methanol, ethanol, ethyl acetate chloroform are used as a organic solvents.[27-30]

Advantages

 Use of specialized equipment is not necessary.

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

 Ease of scale-up if formulation is optimized properly.

Disadvantages

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

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

 Need for diultrafiltration for purification of the drug Nanosuspension, which may render the process costly.

 High amount of surfactant/stabilizer is required as compared to the production techniques described earlier.

Melt emulsification method

In this method drug is dispersed in the aqueous solution of stabilizer and heated above the melting point of the drug and homogenized to give an emulsion. During this process, the sample holder was enwrapped with a heating tape fitted with temperature controller and the temperature of emulsion was maintained above the melting point of the drug. The emulsion was then cooled down either slowly to room temperature or on an icebath.

Advantage

Melt emulsification technique relative to the solvent diffusion method is total avoidance of organic solvents during the production process. [31]

Wet milling

Nanosuspensions are produced by using high shear media mills or pearl mills. The mill 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, 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 media or balls are made of ceramic-sintered aluminium oxide or zirconium oxide or highly cross-linked polystyrene resin with high abrasion resistance. Planetary ball mills (PM100 and PM200; Retsch GmbH and Co., KG, Haan, Germany) is one example of an equipment that can be used to achieve a grind size below 0.1 μm. A nanosuspension of Zn-Insulin with a mean particle size of 150 nm was prepared using the wet milling technique. The major drawbacks of this technology include the erosion of balls/pearls that can leave residues as contaminants in the final product, degradation of the thermolabile drugs due to heat generated during the process and presence of relatively high proportions of particles ≥5 μm.[32]

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 anti-solvent. Higher shear force prevents crystal growth and Ostwald ripening and ensures that the precipitates remain smaller in size.[33]

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. Equipment using this principle includes the M110L and M110S microfluidizers (Microfluidics). Dearn prepared nanosuspensions of atovaquone using the microfluidization process. The major disadvantage of this technique is the high number of passes through the microfluidizer and that the product obtained contains a relatively larger fraction of microparticles.[34]

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. Crystal growth and particle aggregation can be controlled by creating high shear forces using a high-speed stirrer.[35]

Formulation Consideration

Stabilizer

The main function of a stabilizer is to wet the drug particles thoroughly, and to prevent ostwald’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 stabilize 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, povidones, and lecithins.

Organic Solvent

Organic solvents are used in the formulation of Nanosuspension if emulsions or micro emulsions are used as a template. The pharmaceutically acceptable less hazardous water miscible solvent, such as methanol, ethanol, chloroform, ispropanol, and partially water miscible solvents ethyl acetate, ethyl formate, butyl lactate, triacetin, propylene carbonate, benzyl alcohol, are preferent in the formulation over the conventional hazardous solvents, such as dichloromethane.

Co-Surfactants

The choice of co-surfactant is critical when using micro emulsions to formulate Nanosuspensions. Since cosurfactants can greatly influence phase behaviour, the effect of co-surfactant on uptake of the internal phase for selected micro emulsion composition and on drug loading should be investigated.

Other additives

Nanosuspensions may contain additives such as buffers,salts, polyols, osmogent and cryoprotectant.

Post-Production Processing

Post-production processing of Nanosuspensions becomes essential when the drug candidate is highly susceptible to hydrolytic cleavage or chemical degradation. Processing may also be required when the best possible stabilizer is not able to stabilize the Nanosuspension for a longer period of time or there are acceptability restrictions with respect to the desired route.[36]

Characterization of Nanosuspension[37-38]

In-vitro evaluations

 Color, Odor, Taste

 Particle size distribution

 Particle charge (Zeta Potential)

 Crystal morphology

 Dissolution velocity and Saturation solubility

 Density

 pH Value

 Droplet Size

 Viscosity Measurement

 Stability of Nanosuspension

In-vivo Biological Performance

Evaluation for surface-modified Nanosuspension

 Surface hydrophilicity

 Adhesion properties

 Interaction with body proteins

In-vitro evaluations

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.[39]

Particle Size Distribution

Particle size distribution determines the physiochemical behavior of the formulation, such as saturation solubility, dissolution velocity, physical stability, etc. The particle size distribution can be determined by photon correlation spectroscopy (PCS), laser diffraction (LD) and coulter counter multisizer. The PCS method can measure particles in the size range of 3 nm to 3μm and the LD method has a measuring range of 0.05-80μm. The coulter counter multisizer gives the absolute number of particles, in contrast to the LD method, which gives only a relative size distribution. For IV use, particles should be less than 5μm, considering that the smallest size of the capillaries is 5- 6μm and hence a higher particle size can lead to capillary blockade and embolism.[39]

Zeta Potential

Zeta potential is an indication of the stability of the suspension. For a stable suspension stabilized only by electrostatic repulsion, a minimum zeta potential of ±30 mV is required whereas in case of a combined electrostatic and steric stabilizer, a zeta potential of ±20 mV would be sufficient.[40]

Crystal Morphology

To characterize the polymorphic changes due to the impact of high-pressure homogenization in the crystalline structure of the drug, techniques like X-ray diffraction analysis in combination with differential scanning calorimetry or differential thermal analysis can be utilized. Nanosuspensions 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.[41]

Dissolution Velocity and Saturation Solubility

Nanosuspensions have an important advantage over other techniques, that it can increase the dissolution velocity as well as the saturation solubility. These two parameters should be determined in various physiological solutions. The assessment of saturation solubility and dissolution velocity helps in determining the in-vitro behavior of the formulation. Böhm et al. reported an increase in the dissolution pressure as well as dissolution velocity with a reduction in the particle size to the nanometer range. 17 Size reduction leads to an increase in the dissolution pressure.[41]

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.[42]

pH Value

The pH 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.[42]

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.[42]

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 370C by a thermo bath and the samples, for the measurement are to be immersed in it.[43]

Stability of Nanosuspension

The high surface energy of nanosized particles induces agglomeration of the drug crystals. The main function of the stabilizer is to wet the drug particles thoroughly to prevent Ostwald ripening and agglomeration of the Nanosuspension and form a physically stable formulation by providing a steric or an ionic barrier. Typical examples of stabilizers used in Nanosuspensions are cellulosics, poloxamer, polysorbates, lecithin, polyoleate and povidones. Lecithin may be preferred in developing parenteral Nanosuspensions.[43]

APPLICATIONS OF NANOSUSPENSIONS[44-48]

Oral

Oral drug delivery is the most widely preferred route of administration of drugs. But, some drugs possess the problem of limited bioavailability due to poor solubility and absorption which ultimately reduces its efficacy. In such cases, Nanosuspension can solve the problem as it helps in improving the dissolution rate and absorption due to increased surface area and enhanced adhesiveness.

Parenteral

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.

Ocular delivery

Nanosuspension can prove to be a boon for drugs that exhibit poor solubility in lachrymal fluids. Nanosuspensions represent an ideal approach for ocular delivery of hydrophobic drugs due to their inherent ability to improve saturation solubility of drugs.

Pulmonary

Nanosuspensions can be advantageous for delivering drugs that exhibit poor solubility in pulmonary secretion. Currently available approaches for pulmonary delivery such as aerosols or dry powder inhalers possess certain disadvantages such as limited diffusion at required site, less residence time etc, which can be overcome by Nanosuspensions.

Dermal

The nano crystalline form possesses increased saturation solubility resulting in enhanced diffusion of the drug into the skin.

Targeting

The uptake of drug nanoparticles depends on 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 avoided by preparing stealth nanocrystals or by preparing smart crystals i.e. drug particles below particle size of 100nm, which can be used as a targeted drug delivery system. Due to method simplicity, development of nanosuspension is a commercially viable option for targeted delivery.

CONCLUSION:

The nanosuspension can be proved as a gift as the poorly water soluble drugs can be easily formulated into nanosuspension. One of the critical problems associated with poorly soluble drugs is too low bioavailability. There are number of formulation approaches to resolve the problems of low solubility and low bioavailability. Nanosuspension not only solves the problems of poor solubility and bioavailability but also alters the pharmacokinetics of drug and thus improves drug safety and efficacy. Nanosuspensions are submicron colloidal dispersions of nanosized drug particles stabilized by surfactants.Nanosuspension drug delivery has obtained great success in the preparation of insoluble drugs. The nanosuspension technology can confer a series of special characteristics to the drugs, such as the enhanced dissolution rate and saturation solubility. This mini review first described the differences between the nanocrystals and nanosuspensions. Next, the product techniques, the stable measures, the special features, and the routes of administration of the nanosuspensions were reviewed and compared. Finally, some existing shortcomings of the nanosuspensions were mentioned and the perspectives of the nanosuspensions were also made.

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Received on 27.02.2019 Accepted on 21.03.2019

Asian J. Pharm. Res. 2019; 9(2): 123-129.

DOI: 10.5958/2231-5691.2019.00020.0