NANOSUSPENSION

Presented By:

Sanjay Kr. Yadav

Enrolment no: A10647013015

M.Pharma-Pharmaceutics (III Sem)

Amity Institute of Pharmacy

INTRODUCTION

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 andprepared by suitable methods for drug delivery applications through various routes ofadministration”.[1]

PROPERTIES

Usually less than one micron with the average particle size ranging 200-600nm

Drug is maintained in the required crystalline form with reduced particle sizeleads 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

increase adhesiveness.[2]

PREPARATION TECHNIQUES

Top - Down Approach[3]

• Wet Milling

• High Pressure Homogenization

Bottom – up Approach[3]

• Liquid Antisolvent Precipitation

• Liquid Emulsion Technique

• Sonoprecipitation

PREPARATION: WET MILLING

Milling chamber is charged with the milling media, water orsuitable buffer, drug and stabilizer.

Milling media or pearls are rotated at a very high shear rate.[4]

PREPARATION: HIGH PRESSUREHOMINIZATION

Principle:

this method is based on cavitation forces of drug particles in theaqueous phase.

These forces are sufficiently high to convert the drug micro particlesinto nanoparticles.[5]

Method:

Suspension of a drug and surfactant is forced under pressure througha nano-sized aperture valve of a high pressure homogenizer.[5]

PREPARATION: LIQUIDANTISOLVENT PRECIPITATION

Drug is dissolved in an organic solvent and this solution is mixedwith a miscible anti-solvent for precipitation.

In the water-solvent mixture the solubility is low and the drugprecipitates.

Precipitation has also been coupled with high shearprocessing.[6,7]

PREPARATION: LIQUIDEMULSION

Applicable for drugs that are soluble in either volatile organic solvents orpartially water miscible solvents.

This technique includes an organic solvent or mixture solvent loaded with thedrug dispersed in an aqueous phase containing suitable surfactants to forman emulsion.

The organic phase is evaporated under reduced pressure to make drugparticles precipitate instantaneously to form the Nanosuspensions which isstabilized by surfactants.[6]

PREPARATION: SONOPRECIPIATION

Drug is dissolved in organic solvent and stabilizer, surfactantsother ingredients is dissolved in Aqueous solution.

Organic phase is added to aqueous phase then sonicate for 5second at 5 second interval for a total of sonication time of 10minutes.

Keep under vacuum for 1 hour to remove methanol.[8]

CHARACTERIZATION

Particle size distribution:

Determining particle size distribution are photon correlation spectroscopy (PCS), laserdiffraction (LD), dynamic light scattering (DLS) and coulter counter multisizer.[9]

Zeta Potential (Particle charge distribution):

It is determined by Zetasizer.

Nanosuspensions exhibiting good stability, for an electrostatically stabilizedNanosuspensions a minimum zeta potential of ± 30mv is required whereas in the caseof a combined electrostatic and steric stabilization, a minimum zeta potential of ± 20mVis desirable.[10]

CHARACTERIZATION

Crystal structure/ morphology:

Morphological evaluation of drug nanoparticles was conducted throughtransmission electron microscopy (TEM) and scanning electron microscopy(SEM).[9]

Entrapment Efficiency (EE):

Determined by measuring the concentration of free drug in dispersion medium.

The obtained suspension was centrifuged and drug content is determined byusing spectrophotometer or HPLC.[11]

𝐸𝐸 =𝑊𝑖 −𝑊𝑓

𝑊𝑖∗ 100

CHARACTERIZATION

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 bemainly due to a change in surface tension leading to increased saturation solubility.[1]

APPLICATION

Bioavailability enhancement:

Nanosuspensions resolve the problem of poor bioavailability by solving problems of poorsolubility and poor permeability across the membrane.[12]

Target drug delivery:

Nanosuspensions can also be used for targeted delivery as their surface properties andin vivo behaviour can easily be altered by changing either the stabilizer.[12]

APPLICATION

Topical formulations:

Drug nanoparticles can be incorporated into creams and water-free ointments.

The nanocrystalline form leads to an increased saturation solubility of the drug in thetopical dosage form, thus enhancing the diffusion of the drug into the skin.[12]

Mucoadhesion of the nanoparticles:

Nanoparticles orally administered in the form of a suspension diffuse into the liquidmedia and rapidly encounter the mucosal surface.

The particles are immobilized at the intestinal surface by an adhesion mechanismreferred to as bioadhesion.[12]

APPLICATION

Parenteral administration:

Can be administered via different parenteral routes like intra-articular, intraperitoneal,intravenous injection.

For administration by the parenteral route, the drug either has to be solubilized or hasparticle/globule size below 5 μm to avoid capillary blockage.

The current approaches for parenteral delivery include salt formation, solubilizationusing co-solvents, micellar solutions, complexation with cyclodextrin and recentlyliposomes.[12]

Oral administration:

Nanosizing of drugs can lead to a dramatic increase in their oral absorption andsubsequent bioavailability.[12]

REFERENCE

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),1530–1546.

3. Chan, H.K., & Kwok, P. C. L. (2011). Production methods for nanodrug particles using the bottom-up approach. Advanced Drug DeliveryReviews, 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 groundmixtures 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,63(6), 417–426.

8. Jiang, T., Han, N., Zhao, B., Xie, Y., & Wang, S. (2012). Enhanced dissolution rate and oral bioavailability of simvastatin nanocrystal preparedby 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,7(2), 205-217

10. Liang, Y.C. & Binner J.G.P. (2008). Effect of triblock copolymer non-ionic surfactants on the rheology of 3 mol% yttria stabilised zirconiaNanosuspensions. Ceram Int., 34, 293-297.

11. Gupta, D.K., Razdan, B.K., & Bajpai, M. (2014). Formulation and Evaluation of Mefloquine Hydrochloride Nanoparticles, International journal ofpharmaceutical 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 PoorlySoluble Drugs. Curr Nanosci., 5, 417-427.