Preliminary investigation of peroxide levels of Plasdone™ copovidones on the purity of atorvastatin calcium amorphous solid dispersions: Impact of plasticizers on hot melt extrusion processability

Abstract

Trace levels of peroxides in Plasdone™ S630 grades may cause both degradation and corresponding decreases in purity levels of drugs sensitive to oxidation. The present study focused on evaluating the effect of Plasdone™ 630 copovidone grades, namely Plasdone™ S630 (PS630) and Plasdone™ S630 Ultra (PS630U), on the degradation and purity levels of Atorvastatin calcium trihydrate (ACT) amorphous solid dispersions (ASDs) prepared via hot melt extrusion (HME). The influence of plasticizers (Tween 80 and polyethylene glycol 400) on HME processability was studied. Results concluded that extrusion of the binary physical mixture (PM) of drug-polymer (30:70 wt ratio) at 180 °C indicated a high torque value of above 70% of the instrument limit. The extrusion of binary PM in the presence of plasticizers resulted in a decreased torque value (<70%) and processing temperatures of 160 °C, 140 °C, for Tween 80 and PEG 400, respectively. Differential scanning calorimetry and Fourier transform infrared spectroscopy studies of ASDs revealed the formation of an amorphous system with intermolecular interactions between the drug and polymer. The in-vitro dissolution profile of binary and ternary ASDs exhibited a significant increase in dissolution rate (>90% drug release within 30 min) compared to the pure drug (approximately 36% within 30 min). The purity analysis of ACT ASD tablets also exhibited a 0.9%, 0.45%, and 0.2% decrease in purity of ACT for ACT/PS630, ACT/PS630/Tween 80, and ACT/PS630/PEG400 ASDs, respectively, compared to the binary and ternary ASDs containing PS630U polymer. These preliminary study results suggest the enhanced suitability of PS630U over PS630 in developing ASDs for drugs sensitive to oxidation.