Correlationship of Drug-Polymer Miscibility, Molecular Relaxation and Phase Behavior of Dipyridamole Amorphous Solid Dispersions.

Abstract

In present work, a correlationship among quantitative drug-polymer miscibility, molecular relaxation and phase behavior of the dipyridamole (DPD) amorphous solid dispersions (ASDs), prepared with co-povidone (CP), hydroxypropyl methylcellulose phthalate (HPMC P) and hydroxypropyl methylcellulose acetate succinate (HPMC AS) has been investigated. Miscibility predicted using melting point depression approach for DPD with CP, HPMC P and HPMC AS at 25°C was 0.93% w/w, 0.55% w/w and 0.40% w/w, respectively. Stretched relaxation time (τβ) for DPD ASDs, measured using modulated differential scanning calorimetry (MDSC) at common degree of undercooling, was in the order of DPD- CP>DPD-HPMC P>DPD-HPMC AS ASDs. Phase behavior of 12 months aged (25±5°C and 0% RH) spray dried 60% w/w ASDs was tracked using MDSC. Initial ASD samples had homogeneous phase revealed by single glass transition temperature (Tg) in the MDSC. MDSC study of aged ASDs revealed single-phase DPD-CP ASD, amorphous-amorphous and amorphous-crystalline phase separated DPD-HPMC P and DPD-HPMC AS ASDs, respectively. The results were supported by X-ray micro computed tomography and confocal laser scanning microscopy studies. This study demonstrated a profound influence of drug-polymer miscibility on molecular mobility and phase behavior of ASDs. This knowledge can help in designing "physical stable" ASDs.