Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Abstract

Amorphous solid dispersions (ASDs) are popular for enhancing the solubility and bioavailability of poorly water-soluble drugs. Various approaches have been employed to produce ASDs and novel techniques are emerging. This review provides an updated overview of manufacturing techniques for preparing ASDs. As physical stability is a critical quality attribute for ASD, the impact of formulation, equipment, and process variables, together with the downstream processing on physical stability of ASDs have been discussed. Selection strategies are proposed to identify suitable manufacturing methods, which may aid in the development of ASDs with satisfactory physical stability.

Keywords: 3DP, three-dimensional printing; ASDs, amorphous solid dispersions; ASES, aerosol solvent extraction system; Amorphous solid dispersions; CAP, cellulose acetate phthalate; CO2, carbon dioxide; CSG, continuous-spray granulation; Co-precipitation; Downstream processing; Drug delivery; EPAS, evaporative aqueous solution precipitation; Eudragit®, polymethacrylates derivatives; FDM, fused deposition modeling; GAS, gas antisolvent; HME, hot-melt extrusion; HPC, hydroxypropyl cellulose; HPMC, hydroxypropyl methylcellulose; HPMCAS, hydroxypropyl methylcellulose acetate succinate; HPMCP, hypromellose phthalate; Manufacturing; Melting process; PCA, precipitation with compressed fluid antisolvent; PGSS, precipitation from gas-saturated solutions; PLGA, poly(lactic-co-glycolic acid; PVP, polyvinylpyrrolidone; PVPVA, polyvinylpyrrolidone/vinyl acetate; RESS, rapid expansion of a supercritical solution; SAS, supercritical antisolvent; SCFs, supercritical fluids; SEDS, solution-enhanced dispersion by SCF; SLS, selective laser sintering; Selection criteria; Soluplus®, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; Solvent evaporation; Stability; Tg, glass transition temperature; USC, ultrasound compaction; scCO2, supercritical CO2.