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Preparation of Microparticles by Micromixers: Characterization of Oil/Water Process and Prediction of Particle Size

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Purpose.

A descriptive model for microparticle preparation by micromixers was developed to allow prediction of nascent microsphere size and provide a better understanding of a microscale oil/water (O/W) emulsion process.

Methods.

Nascent blank microparticles were prepared by an O/W emulsion method using a micromixer. Seven dimensionless groups were derived from the relevant process parameters. A multiple linear regression model was established on an empirical basis to describe the relationship between the key process parameters and the resulting Sauter particle diameter.

Results.

The investigated micromixer is particularly suitable for processing of low-viscosity systems. The particle size is mainly controlled by flow velocity. Reynolds number and the viscosity ratio were found to be the most important dimensionless groups regarding the preparation procedure. Particle size was predicted with an accuracy up to 100% applying the empirically derived equations.

Conclusions.

An O/W process using micromixers for microparticle preparation with a multitude of influencing parameters was successfully characterized by application of dimensional analysis. Dimensionless groups turned out to be suitable for prediction of microparticle size with high precision.

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Abbreviations

cs:

surfactant concentration of the aqueous phase

dparticle:

Sauter diameter of nascent microparticles

dchannel:

width of product channel

Oh:

Ohnesorge number (dimensionless quotient [viscous forces/inertia driven forces] under simultaneous consideration of the interfacial tension)

Re:

Reynolds number (dimensionless quotient [inertia driven forces/viscous forces])

v:

flow velocity

Vd:

volume of the solvent phase (disperse phase in O/W emulsion process)

Vt:

total volume of formulation

We:

Weber number (dimensionless quotient [interface affecting forces/interfacial tension])

γ:

interfacial tension

ηd:

dynamic viscosity of the solvent phase (disperse phase in O/W emulsion process)

ηc:

dynamic viscosity of the aqueous phase (continuous phase in O/W emulsion process)

ηproduct:

apparent viscosity of nascent microsphere dispersion

ρd:

density of the solvent phase (disperse phase in O/W emulsion process)

ρc:

density of the aqueous phase (continuous phase in O/W emulsion process)

φ:

volume-based phase ratio

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Authors and Affiliations

  1. Schering AG, D-13342, Berlin, Germany

    Kathrin Schalper, Stephan Harnisch & Gesine E. Hildebrand

  2. Department of Pharmaceutics, Biopharmaceutics and Biotechnology, Free University of Berlin, D-12169, Berlin, Germany

    Kathrin Schalper & Rainer H. Müller

Authors
  1. Kathrin Schalper
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  2. Stephan Harnisch
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  4. Gesine E. Hildebrand
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Correspondence to Gesine E. Hildebrand.

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Schalper, K., Harnisch, S., Müller, R. et al. Preparation of Microparticles by Micromixers: Characterization of Oil/Water Process and Prediction of Particle Size. Pharm Res 22, 276–284 (2005). https://doi.org/10.1007/s11095-004-1195-1

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