(645a) Importance of the Rheological Characterization on the Spray Performance of Pharmaceutical Formulations

Importance
of the rheological characterization on the spray performance of pharmaceutical
formulations

T.
Porfirio^1,2*, R.C. Silva¹, J.Vicente¹,
V.Semião²

¹ Hovione Farmaciência SA, Estrada do Paço do Lumiar, 1649-038 Lisbon,
Portugal; *tporfirio@hovione.com

²LAETA, IDMEC, Mechanical Engineering Department, Instituto Superior
Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisbon, Portugal

Spray
drying is one of the most used particle engineering technologies in the pharmaceutical
industry with several enabling applications in modern drug delivery. The
theoretical description of the phenomenon involved in this technology typically
considers two key events – atomization and droplet dying / particle formation. Droplet
size, during the atomization, is the key parameter governing the control of
particle size and bulk density of the spray dried material. The droplet
formation process is strongly influenced by the atomizer design and operating
conditions as well as the feedstock properties viz. viscosity, surface tension
and density [1].

The
determination of feed properties is crucial for an accurate estimation of the
droplet size. However, in the case of non-Newtonian fluids – which are
typically the case of the pharmaceutical formulations used in spray drying – the
properties may vary during atomization due to the high shear at the nozzle
level. Therefore, the rheological behavior of the fluid plays an important role
especially in swirl pressure nozzle in which the shear rate is high by default.
Besides that, an accurate estimation of the shear rate depending on the nozzle
design and operating conditions is paramount to establish a suitable droplet
size correlation.

The
purpose of the present work is to examine the fundamental principles of the liquid
break-up occurring during the atomization process to establish the relationship
between the rheology of the most common organic solutions used in the spray
drying of pharmaceutical formulations and the spray performance and particle
size of the spray dried product. The rheological curves are established using a
rotational rheometer with a cone-plate spindles to achieve shear rate around 10⁵
s^-1. Suitable models are applied to the rheological curves depending
on the fluid behavior and formulation variables i.e. solvent(s) and solid
concentration.

In
order to increase upon the existing knowledge in shear rate estimation for
swirl pressure nozzles, a Computational Fluids Dynamics (CFD) model is benchmarked
in this work and compared with literature data. A velocity and wall shear
stress profile is drawn using such methodology (Figure 1), in tandem with the
experimental feed rheological curves of Newtonian and non-Newtonian fluids,
which in turn is used to establish an understanding and correlation between the
shear rate and the nozzle design / operating conditions.

The
method of the present work can be incorporated in atomization models to
increase the accuracy of spray drying scale-up methods.

Figure 1 – Velocity profile
inside a pressure nozzle

[1]       A.H.
LEFEBVRE, X.F. WANG, Mean drop sizes from pressure-swirl nozzles, J. Propuls. Power.
3 (1987) 11–18. doi:10.2514/3.22946.