Barrier Coated Drug Layered Particles for Formulation Design of an Amorphous Solid Dispersion

Surface phenomena were found to play a distinct role in performance of amorphous celecoxib solid dispersion (ACSD) which comprised of amorphous celecoxib (A-CLB), polyvinylpyrrolidone (PVP) and meglumine (MEG) at 7:2:1 weight ratio. In aqueous media, spray dried ACSD powder filled capsules displayed non-dispersible plug formation, due to cohesive interfacial interactions, that resulted in poor dissolution performance. Additionally, the free surface of ACSD predisposed it to faster devitrification under environmental stress and reduced its shelf life stability. Based on these findings, surface modification was evaluated as a means for its formulation design. Barrier coated-amorphous CLB solid dispersion layered particles (ADLP) were developed by Wurster process, using microcrystalline cellulose as substrate and polyvinyl alcohol (PVA), inulin and polyvinyl alcohol phthalate (PVAP) as coating excipients (at 3% w/w). In aqueous media, barrier coated-ADLP filled capsules were able to preclude the unfavorable interfacial interaction of amorphous particles, and achieved rapid dispersibility and high drug release, in comparison to uncoated ADLP and spray dried ACSD capsules. Physical stability under 25 °C/75% RH and 40 °C/75% RH open conditions indicated crystallization inhibition by 2 to 10-fold (cf. uncoated ADLP) and 9 to 50-fold (cf. spray dried ACSD) with barrier efficiency in the order of inulin