Pharmaceutics · 2021 · 34 citations · 31 references
PharmacyPharmaceuticsPharmacologyDrug DeliveryPharmaceutical FormulationPolymer ChemistryDissolution MediaDrug DissolutionDrug SolubilityFormulation Effects On DissolutionPharmaceutical StabilityStability Of Pharmaceutical FormulationsAmorphous Form StabilityComposition-dependent StabilityDispersionsDissolution Of Amorphous DrugsDissolution Of Solid DispersionsPolymers In Drug FormulationPolymers In Solid DispersionsSolubility - Dissolution Relationship
Amorphization serves as a strategy for the improvement of poor dissolution characteristics of many drug compounds. However, in many formulations the content of polymeric stabilizer is high, which is undesirable from the perspective of future applications. Thus, studying the composition-dependent stability of amorphous solid dispersions seems to be demanded. In this paper, we describe the amorphization of ezetimibe, a lipid-lowering drug, in the spray drying process and investigate the effect of polyvinylpyrrolidone-co-poly(vinyl acetate) (PVP/VA) content on the physical stability and dissolution characteristics of the drug. Fully amorphous systems were obtained when the concentration of the polymer in solid dispersion was as low as 20%. The amorphization led to the dissolution enhancement by even 70%, with a noticeable sudden increase at around 40% of PVP/VA content and very small variations for systems having 66-90% PVP/VA. It was also correlated to wettability characteristics of solid dispersions, which may suggest that in the vicinity of 40% of the polymer content, the behavior of the system becomes independent of the PVP/VA content.
31
Spencer L James, Degu Abate, Kalkidan Hassen Abate et al. · The Lancet · 2018 · 14K citations · Full text