Scaling up the spray drying process from pilot to production scale using an atomized droplet size criterion.
OBJECTIVE
The purpose of this study was to investigate the possibility of producing identical powders in pilot and production scale spray drying equipment by matching the droplet size distributions produced by two differently sized atomizers.


METHODS
Particles were prepared by spray drying solutions of acetaminophen and polyvinylpyrrolidone K-30. The success of the up-scaling was evaluated by comparing the powders in terms of particle size distribution (laser diffraction), crystallinity (XPRD) and morphology (SEM). Furthermore, the influence of process parameters on other product characteristics such as stability and residual volatile content was also evaluated.


RESULTS
The spray drying experiments resulted in spherical, amorphous particles with volumetric median diameters of typically 4-10 microm for pilot scale and 4-30 microm for production scale. The results showed that particles with similar morphology and crystallinity could be produced in the two applied spray dryers. However, scale-up based purely on matching droplet size distributions was not feasible.


CONCLUSIONS
The scale-up criterion did not account for the differences between the droplet-drying gas mixing and residence time distribution within the two spray dryers. Therefore, production scale experiments are required in order to obtain similar product characteristics as in pilot scale.
Thybo
Pia
P
Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. pt@farma.ku.dk
Hovgaard
Lars
L
Lindeløv
Jesper Saederup
JS
Brask
Anders
A
Andersen
Sune Klint
SK
D000082:Acetaminophen / Q000008:administration & dosage / Q000737:chemistry; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000737:chemistry; D002151:Calorimetry; D003890:Desiccation; D004339:Drug Compounding / Q000379:methods*; D000431:Ethanol / Q000032:analysis; D005079:Excipients; D007834:Lasers; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D016062:Porosity; D011205:Povidone; D011208:Powders; D015203:Reproducibility of Results; D012542:Scattering, Radiation; D012996:Solutions; D012997:Solvents; D013500:Surface Tension; D014783:Viscosity; D014961:X-Ray Diffraction
D018712:Analgesics, Non-Narcotic; D005079:Excipients; D011208:Powders; D012996:Solutions; D012997:Solvents; D000082:Acetaminophen; D000431:Ethanol; D011205:Povidone