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Formation of nanosuspensions in bottom-up approach: theories and optimization

  • Ali Ahmadi Tehrani
  • Mohammad Mahdi Omranpoor
  • Alireza Vatanara
  • Mohammad Seyedabadi
  • Vahid RamezaniEmail author
Review Article
First Online:
  • 33 Downloads

Abstract

Background

Nanosuspensions, liquid dispersions with nanometer size distribution, are becoming trendy in pharmaceutical practice to formulate poorly water-soluble drugs and to enhance their bioavailability. Generally, nanosuspensions are produced in two main approaches; top-down or bottom-up. The former is based on size-reduction of large particles via milling or high pressure homogenization. The latter is focused on the mechanisms of nucleation and particle growth.

Methods

In this review, the critical factors influencing the kinetics or dynamics of nucleation and growth are discussed. Subsequently, the mechanisms of nanosuspension instability as well as strategies for stabilization are elaborated. Furthermore, the effects of stabilizers on key parameters of instability as well as the process of choosing an appropriate stabilizer is discussed.

Results

Steric and electrostatic stabilizations or combination of them is essential for nanosuspensions formulation to prevent coagulation. Accordingly, some characteristics of stabilizers play critical role on stability and optimization of nanosuspensions; i.e., HLB and concentration. Nevertheless, after reviewing various articles, it is ascertained that each formulation requires individual selection of surfactants according to the parameters of the particle surface and the medium.

Conclusions

Based on the results, application of excipients such as stabilizers requires proper optimization of type and concentration. This implies that each formulation requires its own optimization process.

Graphical Abstract

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Keywords

Nanosuspensions Bottom-up Nucleation Particle growth Electrostatic stabilization Steric hindrance 

Abbreviations

HPMC

Hydroxypropyl methyl cellulose

MC

Methylcellulose

HPC-SL

Hydroxypropyl cellulose

HPMCP 50

Hydroxypropyl methyl cellulose acetate phthalate

Tween®80

Polysorbate 80

Poloxamers

Polyoxyethylene–polyoxypropylene block copolymer

NaCMC

Sodium carboxy methyl cellulose

PVA

Polyvinylalcohol

SLS

Sodium lauryl sulfate

PVP

Polyvinylpyrrolidone

Labrasol®

CaprylocaproylPolyoxylglycerides

Span 80

Sorbitanmonooleate

Solutol

2-Hydroxyethyl-12-hydroxyoctadecanoate

Span 40

(Sorbitanmonopalmitate)

Plasdone (PVP/VA copolymer)

Polyvinylpyrrolidone-vinyl acetate copolymer

Eudragit®

Polymethacrylates

Vitamin E TPGS

Tocopherol polyethylene glycol succinate

Span 20

Sorbitanmonolaurate

Span 60

Sorbitanmonostearate

Brij® 58

Polyoxyl 20 cetyl ether

Cremophor EL

Polyoxyl 35 castor oil

Volpo 10

Polyoxyl 10 oleyl ether

Crodesta F-160

Sucrose stearate

Crodesta F-110

Sucrose stearate (and) sucrose distearate

Triton X-100

Polyethylene glycol tert-octylphenyl ether

Nomenclature

A

Crystal surface area

D

Diffusion coefficient

d

Nanoparticles diameter

d0

Nanoparticles diameter in the initial time

∆G

Gibbs free energy of a nanoparticle

kB

Boltzmann constant

R

Gas molar constant

RG

Rate of crystal growth

r

Particle radius

S

Degree of supersaturation

T

Absolute temperature

v

Molar volume

η

Viscosity

γ

Surface tension

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Notes

Acknowledgements

The authors gratefully acknowledge the financial support from Shahid Sadoughi University of Medical Sciences.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutics, Faculty of PharmacyShahid Sadoughi University of Medical SciencesYazdIran
  2. 2.Pharmaceutical Research CenterShahid Sadoughi University of Medical SciencesYazdIran
  3. 3.Department of Pharmaceutics, Faculty of PharmacyTehran University of Medical SciencesTehranIran
  4. 4.Department of Pharmacology, School of MedicineBushehr University of Medical SciencesBushehrIran

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