Spray drying formulation of amorphous solid dispersions

Abstract

Spray drying is a well-established manufacturing technique which can be used to formulate amorphous solid dispersions (ASDs) which is an effective strategy to deliver poorly water soluble drugs (PWSDs). However, the inherently complex nature of the spray drying process coupled with specific characteristics of ASDs makes it an interesting area to explore. Numerous diverse factors interact in an inter-dependent manner to determine the final product properties. This review discusses the basic background of ASDs, various formulation and process variables influencing the critical quality attributes (CQAs) of the ASDs and aspects of downstream processing. Also various aspects of spray drying such as instrumentation, thermodynamics, drying kinetics, particle formation process and scale-up challenges are included. Recent advances in the spray-based drying techniques are mentioned along with some future avenues where major research thrust is needed.

Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation

“…Formulating poorly water soluble drugs into amorphous forms is a recognized approach to improve solubility, dissolution and efficacy (36,37). Amino acids have been investigated for improving the dissolution of poorly soluble drugs by forming co-amorphous dispersions (38–42).…”

Spray-dried amorphous isomalt and melibiose, two potential protein-stabilizing excipients

“…A droplet/particle becomes sticky when the droplet temperature is higher than its surface T g and uneven distribution of water within the drying particles has a significant impact on the outcome (Adhikari et al, 2005). During spray drying, the outlet temperature is the maximum temperature experienced by the particles, however, solvent evaporation provides efficient cooling and the droplet temperature begins to rise significantly only after the evaporation rate slows down (Anandharamakrishnan et al, 2010;Singh and Van den Mooter, 2016). Isomalt droplets/particles would have experienced higher temperatures for a longer time if the evaporation rate had reduced at an earlier stage compared to sucrose.…”

“…Particles produced by spray drying are often amorphous because of the millisecond time scale of droplet-to-particle transition, not giving molecules enough time to arrange and crystallize (Singh and Van den Mooter, 2016). The amorphous form is thermodynamically unstable and it is energetically driven towards a more stable crystalline state.…”

“…Spray drying is a unit operation drying process for fast transformation of liquids to powders with controllable particle properties such as size, shape and surface composition (Paudel et al, 2013;Singh and Van den Mooter, 2016;Vehring, 2008). Particles produced by spray drying are often amorphous because of the millisecond time scale of droplet-to-particle transition, not giving molecules enough time to arrange and crystallize (Singh and Van den Mooter, 2016).…”

Pharmaceutical Applications of Electrospraying

“…The extremely rapid solvent evaporation rate also contributes to the generation of the amorphous state of the APIs in the systems, that is, amorphous SDs as API molecules are "frozen" randomly and instantly in the solid polymer matrix and preserved as solid solution. Spray drying, one of the most commonly used techniques for producing amorphous SDs based on rapid rate of solvent removal 106,107 is another simple and comparable method and could be argued as a superior alternative of electrospraying. 108 However, we could expect an additional positive contribution to the amorphization in case of electrospraying because it generates much smaller droplets compared to the ones from spray drying which will facilitate an even faster solvent removal.…”