it details abt preparation and evaluation of nanosuspension
Published on: Mar 3, 2016
Transcripts - Nanosuspension
Sanjay Kr. Yadav
Enrolment no: A10647013015
M.Pharma-Pharmaceutics (III Sem)
Amity Institute of Pharmacy
A PHARMACEUTICAL NANOSUSPENSION IS DEFINED AS:
“Very finely colloid biphasic, dispersed and solid drug particles in aqueous vehicle,
size below 1µm without any matrix material stabilized by surfactant and polymers and
prepared by suitable methods for drug delivery applications through various routes of
Usually less than one micron with the average particle size ranging 200-
Drug is maintained in the required crystalline form with reduced particle size
leads to the increased dissolution rate and enhances the bioavailability
Increased insolubility and dissolution velocity
Increase in apparent saturated solubility Cs, and Surface area.
Increased dissolution velocity
Top - Down Approach
• Wet Milling
• High Pressure Homogenization
Bottom – up Approach
• Liquid Antisolvent Precipitation
• Liquid Emulsion Technique
PREPARATION: WET MILLING
Milling chamber is charged with the milling media, water or
suitable buffer, drug and stabilizer.
Milling media or pearls are rotated at a very high shear rate.
PREPARATION: HIGH PRESSURE
this method is based on cavitation forces of drug particles in the
These forces are sufficiently high to convert the drug micro particles
Suspension of a drug and surfactant is forced under pressure through
a nano-sized aperture valve of a high pressure homogenizer.
Drug is dissolved in an organic solvent and this solution is mixed
with a miscible anti-solvent for precipitation.
In the water-solvent mixture the solubility is low and the drug
Precipitation has also been coupled with high shear
Applicable for drugs that are soluble in either volatile organic solvents or
partially water miscible solvents.
This technique includes an organic solvent or mixture solvent loaded with the
drug dispersed in an aqueous phase containing suitable surfactants to form
The organic phase is evaporated under reduced pressure to make drug
particles precipitate instantaneously to form the Nanosuspensions which is
stabilized by surfactants.
Drug is dissolved in organic solvent and stabilizer, surfactants
other ingredients is dissolved in Aqueous solution.
Organic phase is added to aqueous phase then sonicate for 5
second at 5 second interval for a total of sonication time of 10
Keep under vacuum for 1 hour to remove methanol.
Particle size distribution:
Determining particle size distribution are photon correlation spectroscopy (PCS), laser
diffraction (LD), dynamic light scattering (DLS) and coulter counter multisizer.
Zeta Potential (Particle charge distribution):
It is determined by Zetasizer.
Nanosuspensions exhibiting good stability, for an electrostatically stabilized
Nanosuspensions a minimum zeta potential of ± 30mv is required whereas in the case
of a combined electrostatic and steric stabilization, a minimum zeta potential of ± 20mV
Crystal structure/ morphology:
Morphological evaluation of drug nanoparticles was conducted through
transmission electron microscopy (TEM) and scanning electron microscopy
Entrapment Efficiency (EE):
Determined by measuring the concentration of free drug in dispersion medium.
The obtained suspension was centrifuged and drug content is determined by
using spectrophotometer or HPLC.
Saturation solubility and dissolution velocity:
Nanosuspensions increase the dissolution velocity and saturation solubility.
Size reduction leads to increase in the dissolution pressure.
An increase in solubility that occurs with relatively low particle size reduction may be
mainly due to a change in surface tension leading to increased saturation solubility.
Nanosuspensions resolve the problem of poor bioavailability by solving problems of poor
solubility and poor permeability across the membrane.
Target drug delivery:
Nanosuspensions can also be used for targeted delivery as their surface properties and
in vivo behaviour can easily be altered by changing either the stabilizer.
Drug nanoparticles can be incorporated into creams and water-free ointments.
The nanocrystalline form leads to an increased saturation solubility of the drug in the
topical dosage form, thus enhancing the diffusion of the drug into the skin.
Mucoadhesion of the nanoparticles:
Nanoparticles orally administered in the form of a suspension 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.
Can be administered via different parenteral routes like intra-articular, intraperitoneal,
For administration by the parenteral route, the drug either has to be solubilized or has
particle/globule size below 5 μm to avoid capillary blockage.
The current approaches for parenteral delivery include salt formation, solubilization
using co-solvents, micellar solutions, complexation with cyclodextrin and recently
Nanosizing of drugs can lead to a dramatic increase in their oral absorption and
1. Dhanapal, R., & Ratna, J. V. (2012). Nanosuspension technology in drug delivery: A Review. International journal of Pharmacy Review &
Research, (1), 46–52
2. Agrawal, U., Sharma, R., Gupta, M., & Vyas, S. P. (2014). Is nanotechnology a boon for oral drug delivery? Drug Discovery Today, 19(10),
3. Chan, H.K., & Kwok, P. C. L. (2011). Production methods for nanodrug particles using the bottom-up approach. Advanced Drug Delivery
Reviews, 63(6), 406–416.
4. Itoh, K., Pongpeerapat, A., Tozuka, Y., Oguchi, T. & Yamamoto, K. (2003). Nanoparticle formation of poorly water soluble drugs from ternary ground
mixtures with PVP and SDS. Chem Pharm Bull., 51,171-4.
5. Patravale, V.B., Date, A. A. & Kulkarni, R. M. (2004). Nanosuspensions: a promising drug delivery strategy. J Pharm Pharmacol., 56, 827-40.
6. Margulis-Goshen, K., & Magdassi, S. (2009). Formation of simvastatin nanoparticles from microemulsion. Nanomedicine: Nanotechnology,
Biology, and Medicine, 5(3), 274–281.
7. Addio, S. M., & Prud’homme, R. K. (2011). Controlling drug nanoparticle formation by rapid precipitation. Advanced Drug Delivery Reviews,
8. Jiang, T., Han, N., Zhao, B., Xie, Y., & Wang, S. (2012). Enhanced dissolution rate and oral bioavailability of simvastatin nanocrystal prepared
by sonoprecipitation. Drug Development and Industrial Pharmacy, 38(10), 1230–1239.
9. Shid, R.L., Dhole, S. N., Kulkarni, N., & Shid, S. L. (2014). Formulation and Evaluation of Nanosuspension Delivery System for Simvastatin,
10. Liang, Y.C. & Binner J.G.P. (2008). Effect of triblock copolymer non-ionic surfactants on the rheology of 3 mol% yttria stabilised zirconia
Nanosuspensions. Ceram Int., 34, 293-297.
11. Gupta, D.K., Razdan, B.K., & Bajpai, M. (2014). Formulation and Evaluation of Mefloquine Hydrochloride Nanoparticles, International journal of
pharmaceutical sciences and nanotechnology, 7(1), 2377–2386.
12. Xiaohui, P.U., Sun, J., Li, M. & Zhonggui H. (2009). Formulation of Nanosuspensions as a New Approach for the Delivery of Poorly
Soluble Drugs. Curr Nanosci., 5, 417-427.