Solvent evaporation method in solid dispersion preparation – Spray drying granulation technique (P6)

Fluid-bed granulation (fluid-bed dryer) ) is a widely used solvent evaporation method in solid dispersion formulation to improve drug properties such as solubility, uniform particle size, flowability, and good compressibility. This is a “one-pot” method, combining multiple production steps such as mixing, granulating, and drying in just one device, optimizing time and process. Fluid bed granulation is particularly effective in creating uniform particles with controlled moisture content, improving tableting ability and final product quality.

Principle

Fluid bed granulation operates on the principle of fluidization – the process of a stream of air being blown through a layer of powder or granules at a high enough velocity to cause these particles to move and circulate with the spray receiving process. In solid dispersion formulation, the drug and polymer solution is sprayed onto the excipient and the solvent is evaporated to create a solid dispersion.

This process consists of three main steps:

• • Dry mixing: The raw materials are sprayed with hot air to create a uniform dispersion and ensure thorough mixing of the ingredients.
  • Spraying binder solution: The solution is sprayed onto the raw material particles in a fluidized state, connecting the particles together to form particles of the desired size.
  • Drying: After the granulation process is complete, the hot air drying system will remove moisture from the particles.

The simultaneous combination of granulation and drying steps helps to create particles that tend to be spherical and more porous than wet granulation using a high-speed mixer.

Advantages and disadvantages

Advantages:

• • Integrated process: Fluid bed granulation combines mixing, granulation and drying in the same equipment, optimizing time, minimizing the number of equipment required and avoiding potential problems with product stability.
  • Uniformity: The resulting particles are uniform in size and shape, improving compressibility and product stability.
  • Temperature optimization: This method can operate at low temperatures, suitable for heat-sensitive drugs.
  • Good moisture control: The ability to control moisture and particle size helps the final product to have the appropriate moisture and hardness.

Disadvantages:

• • Particle agglomeration: In some cases, improper adjustment can lead to excessive particle sticking or agglomeration, making subsequent tableting difficult.

Application

Products with solid dispersion structure are produced by fluid bed granulation method (Fluid-Bed Dryer) as follows:

Trade name	Chemical name	Manufacturing technique		Company	Year
Sporanox ®	Itraconazole	Fluid bed granulation		Janssen	1992
Prograf ®	Tacrolimus	Spray drying		Astellas Pharma	1994

This technology is also applied in the production of solid dispersions with controlled release (CR) or immediate release (IR) capabilities, such as dipyridamole, nifedipine-HPMC ASD, and silymarin-PVPP ASD.

References

[1] S. V. Bhujbal et al., “Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies,” vol. 11, no. 8, pp. 2505-2536, 2021.

[2] Y. Qiu, Y. Chen, G. G. Zhang, L. Yu, and R. V. Mantri, Developing solid oral dosage forms: pharmaceutical theory and practice. Academic press, 2016.