Method Development To Prepare Spray Dry Dispersions For Early Development Compounds

To determine critical process parameters which influence the characteristics of spray dried materials for quick small scale formulation screening using DOE.

Different polymers (PVP-K30 in dichloromethane and HPMCAS LF in 2:1 w/w of dichloromethane: methanol) were spray dried at a batch size of approximately 50 g using a Buchi B-290 equipment under different experimental conditions. After the initial experiments, a full factorial study (four factors and two center points) was conducted to understand the influence of polymer (HPMCAS) concentration (2 to 6%), inlet temperature (40 to 60°C), atomization air flow (600-742 L/h), and liquid feed rate (30 to 70 g/min) on the particle size distribution (by laser diffraction), outlet temperature, yield, and stickiness of the spray dried material.

As expected a narrow range of micronize size particles was prepared under the experimental conditions employed in this study which can be attributed to equipment scale/design and polymer/solvent system. Particles ranging from 4.5 to 10.6 μm (mass median diameter) was obtained from spray drying solutions containing PVP (5-10% w/w) in dichloromethane. For the HPMCAS system, polymer concentration in spray dry solution affects the particle size whereas other factors are not statistically significant. Outlet temperature is a function of the inlet temperature, feed rate and atomization air flow. The yield has a strong, non-linear correlation with polymer concentration (p<0.05). Atomization air flow, inlet temperature and interactions of atomization air flow with polymer concentration also affected the yield. The stickiness of the particles can be controlled by polymer concentration, atomization air flow and their interactions.

A quick statistical and material sparing approach is a useful process development tool for the preparation of solid dispersions by spray drying during early formulation screening. The data also suggested that polymer concentration is the most dominating factor that influences size, yield and properties of a solid dispersion. Although a higher concentration of polymer is often desired, a lower concentration is often required for spray drying of solid dispersions for APIs of low solubility even in organic solvents.