Review Article Nanosuspension - A Novel Carrier For Lipidic Drug Transfer
Review Article Nanosuspension - A Novel Carrier For Lipidic Drug Transfer
Review Article Nanosuspension - A Novel Carrier For Lipidic Drug Transfer
Review Article
Nanosuspension – A Novel Carrier For Lipidic Drug Transfer
Abhyangshree Nandkumar Mane*, Sagar Suresh Gilda, Amruta Avinash Ghadge, Nikhil Rajendra Bhosekar,
Rohit Rajendra Bhosale
Department of Pharmaceutics, Satara College of Pharmacy, Satara, Maharashtra, India.
*Corresponding author
Abhyangshree Nandkumar Mane
Email:
Abstract: Solubility is the crucial factor for drug effectiveness, independence of the route of administration. Large
proportion of newly discovered drugs are water insoluble & therefore poorly bioavailable contributing to desert
development effort. Nanosuspensions have emerged as a promising strategy for the efficicent delivery of hydrophilic
drugs because of their versatile features &unique advantages. The reduction of drug particles into submicron range leads
to a significant increase in dissolution rate & therefore enhances bioavailability. Nanosuspension contain submicron
colloidal dispersion of the pharmaceutical active ingredient particles in a liquid phase stabilised by surfactant.
Nanosuspensions can be delivered by oral & non-oral route of administration. Study is focused on various methods of
preparation with advantages & disadvantages, characterization properties, applications.
Keywords: Nanosuspension, Bioavailability, Colloid, Surfactant, Solubility enhancement.
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water & stabilizer is fed into the milling chamber & temperatures. The typical residence time generated for a
processed into nano-crystalline dispersion & the milling nanometer-sized dispersion with a mean diameter of
media or pearls are then rotated at a very high shear <200nm is 30-60min [19].
rate. The milling process is performed under controlled
Homogenization in non-aqueous media (Nanopure) - below the freezing point & hence are called “deep-
Nanopure is suspension homogenized in water free freeze” homogenization. The result obtained were
media or water mixtures i.e. the drug suspensions in the comparable to dissocubes & hence can be used
non-aqueous media were homogenized at 0oC or even
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effectively for thermolabile substance at milder such as PVP, PEG, HPMC has been used.
conditions. Physiochemical properties & dissolution of poorly
water soluble drugs were improved by co-grinding
Combined precipitation & homogenization because of an improvement in the surface polarity &
(Nanoedge) - transformation from a crystalline to an amorphous drug.
The drug is dissolved in an organic solvent & this Dry co-grinding can be carried out easily &
solution is mixed with a miscible anti-solvent for economically & can be conducted without organic
precipitation. In the water-solvent mixture the solubility solvents. The co-grinding technique can reduce
is low & the drug precipitates. Precipitation has also particles to the submicron level & a stable amorphous
been coupled with high shear processing. The basic solid can be obtained [18].
principles of Nanoedge are the same as that of
precipitation & homogenization. A combination of Emulsion as template –
these techniques results in smaller particle size & better Apart from the use of emulsion as a drug delivery
stability in a shorter time [26]. vehicle, they can also be used as template to produce
nanosuspensions. The use of emulsion as templates is
Nanojet technology – applicable for those drugs that are soluble in either
This technique is also called as „opposite stream‟ uses a volatile organic solvent or partially water-miscible
chamber where a stream of suspension is divided into solvents. Such solvents can be used as the dispersed
two or more parts, which colloid with each other at high phase of the emulsion. There are two ways of
pressure upto 4000 bar at high velocity of 1000m/s. The fabricating drugs nanosuspensions by emulsification
high shear force produces during the process result in method. In the first method, an organic solvent or
particle size reduction [25]. mixture of solvents loaded with drug is dispersed in the
aqueous phase containing suitable surfactant to form an
Emulsification-solvent evapouration techniques - emulsion. The organic phase is then evaporated under
This technique involves preparing a solution of drug reduced pressure so that the drug particles precipitates
followed by its emulsification in another liquid that is a instantaneously to form a nanosuspension stabilized by
non-solvent for the drug. Evaporation of the solvent surfactants. Since one particle is formed in each
leads to precipitation of the drug [20]. emulsion droplet, it is possible to control the particle
size of the nanosuspension by controlling the size of the
Supercritical fluid method – emulsion. Optimizing the surfactant composition
Supercritical fluid technology can be used to produce increases intake of organic phase & ultimately the drug
nanoparticles from drug solutions. The various methods loading in the emulsion. Originally, organic solvents
attempted are rapid expansion of supercritical solution such as methylene chloride & chloroform were used.
process (RESS), supercritical anti-solvent process &
precipitation with compressed anti-solvent process Characterization of Nanosuspension-
(PCA). The RESS involves expansion of the drug 1) Mean particle size & particle size distribution.
solution in supercritical fluid through a nozzle, which The mean particle size & the width of particle size
leads to loss of solvent power of the supercritical fluid distribution are important characterization parameters
resulting in precipitation of the drug as fine particles. In as they govern the saturation solubility, dissolution
the PCA method, the drug solution is atomized into a velocity, physical stability & even biological
chamber containing compressed Co2. As the solvent is performance of nanosuspensions [27].
removed, the solution gets supersaturation & thus
precipitates as fine crystals. The supercritical anti- 2) Crystalline state & particle morphology.
solvent process uses a supercritical fluid in which a The assement of the crystalline state & particle
drug is poorly soluble & a solvent for the drug that is morphology together helps in understanding the
also miscible with the supercritical fluid. The drug polymorphic or morphological changes that a drug
solution is injected into the supercritical fluid & the might undergo when subjected to nanosizing.
solvent gets extracted by the supercritical fluid & the Additionally, when nanosuspensions are prepared drug
drug solution gets supersaturated. The drug is then particles in an amorphous state are likely to be
precipitated as fine crystals [26]. generated. Hence, it is essential to investigate the extent
of amorphous drug nanoparticles generated during the
Dry co-grinding – production of nanosuspensions. The changes in the
Nanosuspensions prepared by high pressure physical state of the drug particles as well as the extent
homogenization & media milling using pearl ball mill of the amorphous fraction can be determined by X-ray
are wet –grinding processes. Recently, nanosuspensions diffraction analysis & can be supplemented by
can be obtained by dry milling techniques. Successful differential scanning calorimetry. In order to get a
work in preparing stable nanosuspensions using dry- actual idea of particle morphology, scanning electron
grinding of poorly soluble drugs with soluble polymers microscopy is preferred [6].
& copolymers after dispersing in a liquid media has
been reported. Many soluble polymers & co-polymers 3) Particle charge (Zeta potential)
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The determination of zeta potential of nanosuspension increase in their oral absorption & subsequently
is essential as it gives an idea about the physical biovailability. The oral administration of naproxen
stability of the nanosuspension. The zeta potential of a nanoparticles leads to an area under the curve of 97.5
nanosuspension is governed by both the stabilizer & the mg-h/l compared with just 44.7 mg-h/l for naprosyn
drug itself. In order to obtain a nonosuspension suspensions & 32.7 mg-h/l for anapro tablets. Oral
exhibiting good stability, for an electrostatically administration of gonadotrophin inhibitor Danazol as a
stabilized nanosuspension a minimum zeta potential of nanosuspensions leads to an absolute bioavailability of
30mV is required whereas in the case of a combined 82.3 & the convectional dispersion only to 5.2%. A
electrostatic & steric stabilization, a minimum zeta nanosuspension of Amphotericin B developed by
potential of 20mV is desirable [28]. Kayser el al.Showed a significant improvement in its
oral absorption in comparison with the convectional
4) pH commercial formulation [6].
The pH of the nanosuspensions can be easily measured
by using pH meter [26]. 2) Parenteral Drug Delivery
One of the important applications of nanosuspension
5) Osmolarity technology is the formulation of intravenously
Practically, osmolarity of nanosuspension can be administered products. IV administration results in
measured by using Osmometer [26]. several advantages, such as administration of poorly
soluble drugs without using a higher concentration of
6) Saturation solubility & Dissolution velocity toxic co-solvent, improving the therapeutic effect of the
Nanosuspensions have an important advantage over drug available as convectional oral formulations &
other techniques, that it can increase the dissolution targeting the drug to macrophages & the pathogenic
velocity as well as the saturation solubility. The micro-organism residing in the microphages. Injectable
saturation solubility of the drug in different nanosuspensions of poorly soluble drug tarazepide have
physiological buffer as well as at different temperature been prepared to overcome the limited success achieved
should be assessed using methods described in the using convectional solubilising techniques, such as use
literature. The investigation of the dissolution velocity of surfactants, cyclodextrins etc. To improve
of nanosuspensions reflects the advantages that can be bioavailability [2].
achieved over convectional formulations, especially
when designing the sustained-release dosage forms 3) Pulmonary Drug Delivery
based on nanoparticulate drugs. The assessment of Aqueous nanosuspensions can be nebulized using
saturation solubility & dissolution velocity helps in mechanical or ultrasonic nebulizer for lung delivery.
determining the vitro behaviour of the formulation [1]. Basically the nanosuspensions can be used in all
nebulizers. The dispersions can be relatively high
7) Surface Hydrophilicy concentrated. Due to presence of many small particles
For intravenous injected nanosuspensions, additional instead of a few large microparticles, all aerosol droplet
parameters need to be determined which affect the in are likely to contain drug nanoparticles. Budesonide, a
vivo fate of the drug nanoparticles. Surface poorly water-soluble corticosteroid, has been
hydrophilicy is considered as one of the important successfully prepared as a nanosuspension for
parameters affecting the in vivo organ distribution after pulmonary delivery. A good relationship was obtained
i.v. injection. The surface hydrophobicity determines between increasing the drug concentration in the
the interaction with cells prior to phagocytosis & in formulation & the number of micrograms of drug
addition, it is a relevant parameter for the adsorption of delivered per actuation. In addition, buparvaquone
plasma proteins the key factor for organ distribution. To nanosuspensions were formulated for treatment of lung
avoid artefact, the surface hydrophobicity needs to be infections by using nebulizers [18].
determined in the original environment of the drug
nanoparticles, which means in aqueous dispersion 4) Topical Formulations
medium. A suitable technique is hydrophobic Drug nanoparticles can be incorporated into creams &
interaction chromatography (HIC), previously water free ointments. The nanocrystalline forms leads to
employed to determine the surface hydrophobicity of an increased saturation solubility of drug in the topical
bacteria, & then transferred to the characterization of dosage form, thus enhancing the diffusion of the drug
nanoparticluate drug carriers. into the skin [23].
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of the drug allows its prolonged residence in the cul-de- delivery of ibuprofen, European journal of
sac, giving sustained release of the drug [10]. pharmaceutical science, 2002; 16, 53-61.
8. Panayiotis P, Mahesh V, Robert S; Advance in
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Acknowledgement- 13. Dressman J, Amindon C, Shaha V; Dissolution
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