Understanding the impact of spray drying temperature on the dissolution behavior of a HPMC-AS spray dried formulation

Spray dried dispersion (SDD) is increasingly used in solid dose formulations for poorly soluble active pharmaceutical ingredients (APIs). Dissolution was studied on a HPMC-AS based SDD and one important SDD manufacturing parameter, the spray drying outlet temperature (T_out), was found to significantly affect the dissolution rate of the tablet formulation containing the SDD. The dissolution rate of tablets containing SDD made at higher T_out was slower than those containing SDD made at lower T_out. When SDD powder dissolution was tested using a dissolution apparatus equipped with an intrinsic dissolution device, a similar trend of dissolution rate was observed. SEM imaging and other physical characterizations showed that the morphology of the SDD material contained a mixture of hollow sphere particles and collapsed, wrinkled raisin-like particles. Higher T_out produced a higher ratio of hollow sphere particles than lower T_out. It was found that although SDD T_out and particle morphology did impact the drug product properties such as tablet hardness, the dissolution rate difference was mainly attributed to the SDD particle dissolution instead of tablet disintegration for the model SDD formulation studied. To further understand the SDD particle dissolution rate differences at different SDD T_out, the raisin-like particles and the hollow sphere particles from the same batch of SDD were physically separated by density for dissolution study. The separated hollow sphere SDD particles showed slower dissolution compared to the raisin-like SDD particles in both SDD powder form and drug product tablet form. Additional physical characterization and surface analysis were conducted on the SDD materials to understand the mechanism of the dissolution rate difference. Surface composition analysis by x-ray photoelectron spectroscopy (XPS) suggested that a higher concentration of the drug substance was present at the surface of the hollow sphere SDD particles than raisin-like particles. It is possible that the higher concentration of the poor soluble API on the surface of hollow sphere SDD particles resulted in more hydrophobic surface which led to slower dissolution rate.