Spray drying an active pharmaceutical ingredient (API) with a polymer excipient is a common processing technique for solubility enhancement platforms. Formulators desire the highest possible spray solution feed concentration, but viscosity restrictions usually limit the solids concentration at which polymer/API solutions can be successfully atomized. This study details experiments to compare use of AFFINISOLTM HPMCAS 126G with a developmental chemically equivalent lower viscosity grade at higher feed solution concentrations, but with minimal process parameter intervention and optimization. Powder morphology is examined as a function of spray solution concentrations and viscosities to determine differences in product properties.
Polymers selected for assessment were AFFINISOLTM HPMCAS 126G (12% acetate, 6% succinate) and a developmental chemically equivalent grade (HP HPMCAS 126) with reduced solution viscosity. The polymer was dissolved in acetone with griseofulvin in a 1:9 drug to polymer ratio for all solutions. Solution total solids concentrations were varied from 8 to 13 wt% for AFFINISOLTM HPMCAS 126G, and from 8 to 30 wt% for HP HPMCAS 126. HP HPMCAS 126 solutions were made to match the AFFINISOLTM HPMCAS 126G solutions both in mass loading and in solution viscosity, followed by assessing concentrations above 20 wt%. Spray drying was conducted on a GEA MOBILE MINORTM R&D spray drier with chamber extension, using both two-fluid and pressure swirl nozzles at inlet temperature of 85 °C for both nozzles. Nozzle pressure, spray rate and yield were recorded for all runs. Powder morphology was assessed by measurement of bulk density, krypton BET surface area, laser diffraction particle size distribution and scanning electron microscopy.
Feed concentrations of standard grade AFFINISOL HPMCAS 126G above 13 wt% were inoperable due to viscosity limits, so direct comparison to HP at high loadings is not possible. Effective production of spray dried powders was demonstrated for HP HPMCAS feed solutions from 8 wt% to 20 wt% with minimal process intervention. Once concentration was increased above 20 wt%, yields began to fall from 80-90% to under 60%. For the two-fluid nozzle, bulk density decreased with increasing solution concentration from 0.15 g/cc at 8 wt% to 0.07 g/cc at 30 wt%. This was accompanied by a decrease in BET surface area from 1.49 to 0.61 m2/g, indicating formation of larger, smoother particles. SEM shows that the decrease in density at high feed concentrations is due to a morphology change from buckled, collapsed spheres to elongated twisted particles. At intermediate solution concentrations of 20 wt%, an intermixing of the two morphologies is seen (Figure 1).
For the pressure swirl nozzle, the decrease in surface area from 8 wt% to 30 wt% was much more subtle, and the surface areas were overall lower, going from 0.41 to 0.24 m2/g. The bulk densities actually increased with increasing feed concentration, from 0.17 to 0.22 g/cc. These higher density powders had generally more spherical morphology, and practically none of the elongated solids seen in the product dried from the two fluid nozzle (Figure 2).
Both nozzles were shown to effectively spray dry feeds of griseofulvin / HP HPMCAS up to 20 wt% solids at essentially a single set of processing conditions, with reasonable yields and suitable product morphologies. It appeared that some concentration value between 20 and 25 wt% was the maximum solids content suitable for the given parameters, and spray drying yield and product morphology were compromised between 25 and 30 wt% solids. Distinct morphological changes were observed for the two fluid nozzle product at high concentrations under these conditions. Further process development of nozzle configuration, nozzle size, and inlet/outlet temperature and would be needed to optimize the atomization conditions for each nozzle to improve product properties at higher feed solution solid content.
William Porter– The Dow Chemical Company
Tom Watson– The Dow Chemical Company, Michigan
Erica Anderson– GEA Pharma Systems, Maryland
Tyron Lunn– GEA Process Engineering, Inc., Maryland
Jessica Zombek– GEA Process Engineering, Inc.
Andrew Birkmire– GEA Pharma Systems, Maryland