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



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.


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.


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.


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


Nanosuspensions Bottom-up Nucleation Particle growth Electrostatic stabilization Steric hindrance 



Hydroxypropyl methyl cellulose




Hydroxypropyl cellulose


Hydroxypropyl methyl cellulose acetate phthalate


Polysorbate 80


Polyoxyethylene–polyoxypropylene block copolymer


Sodium carboxy methyl cellulose




Sodium lauryl sulfate





Span 80




Span 40


Plasdone (PVP/VA copolymer)

Polyvinylpyrrolidone-vinyl acetate copolymer



Vitamin E TPGS

Tocopherol polyethylene glycol succinate

Span 20


Span 60


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



Crystal surface area


Diffusion coefficient


Nanoparticles diameter


Nanoparticles diameter in the initial time


Gibbs free energy of a nanoparticle


Boltzmann constant


Gas molar constant


Rate of crystal growth


Particle radius


Degree of supersaturation


Absolute temperature


Molar volume




Surface tension



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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