Miscibility and thermal properties of poly(vinylpyrrolidone-vinyl acetate)/lamivudine and tenofovir binary blends prepared by hot melt extrusion

Abstract

Preparation of amorphous solid dispersions (ASD) by hot melt extrusion (HME) of poly(vinylpyrrolidone-vinyl acetate) (Kollidon) and the active pharmaceutical ingredients (API) Lamivudine (3TC) and Tenofovir Disoproxyl Fumarate (TDF) was investigated aiming to study their miscibility and thermal behavior. These two drugs are currently used as drugs in first line treatment of patients with Acquired Immunodeficiency Syndrome (AIDS). In order to predetermine parameters for extrusion and the maximum concentration of API to be used without any recrystallization, binary blends were first processed in the mixing chamber at 130°C using a roller type rotor at 10, 20 and 30 rpm for 7 min, giving rise to ASD of both API, at least up to 20 wt% of the drug. Both 3TC and TDF were then extruded individually with Kollidon in a single screw extruder. HME produced ASD with high concentration of both Kollidon/API combinations, being part of the API soluble in the polymer matrix. From HME, Kollidon/3TC forms ASD in concentration up to 50 wt%, but from 30 wt% 3TC, the ASD has no time stability, showing recrystallization in less than 5 months, while the Kollidon/TDF system forms ASD up to 30 wt% of TDF, but it has aging stability inferior to 4 months.