Journal Article

Role of Surfactants on Release Performance of Amorphous Solid Dispersions of Ritonavir and Copovidone

Zhang, Geoff G. Z., Indulkar, Anura S., Taylor, Lynne S., Lou, Xiaochun

2022

Overview

Purpose To understand the role of different surfactants, incorporated into amorphous solid dispersions (ASDs) of ritonavir and copovidone, in terms of their impact on release, phase behavior and stabilization of amorphous precipitates formed following drug release. Methods Ternary ASDs with ritonavir, copovidone and surfactants (30:70:5 w/w/w) were prepared by rotary evaporation. ASD release performance was tested using Wood’s intrinsic dissolution rate apparatus and compared to the binary drug-polymer ASD with 30% drug loading. Size measurement of amorphous droplets was performed using dynamic light scattering. Solid state characterization was performed using attenuated total reflectance-infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy. Results All surfactant-containing ASDs showed improvement over the binary ASD. Span 85 and D-α-tocopheryl polyethylene glycol succinate (TPGS) showed complete release with no evidence of AAPS or crystallization whereas Span 20 and Tween 80 showed < 50% release with amorphous amorphous phase separation (AAPS). Span 20 also induced solution crystallization. Sodium dodecyl sulfate (SDS) showed very rapid, albeit incomplete (~ 80%) release. AAPS was not observed with SDS. However, crystallization on the dissolving solid surface was noted. Span 20 and TPGS formed the smallest and most size-stable droplets with ~ 1 µm size whereas coalescence was noted with other surfactants. Conclusions Surfactants improved the release performance relative to the binary ASD. Different surfactant types impacted overall performance to varying extents and affected different attributes. Overall, Span 85 showed best performance (complete release, no crystallization/AAPS and small droplet size). Correlation between physicochemical properties and surfactant performance was not observed.

• Publisher: Springer US,Springer,Springer Nature B.V
• Subject: Antiretroviral drugs / Antiviral drugs / Biochemistry / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Biomedicine / Calorimetry / Comparative analysis / Crystallization / Differential scanning calorimetry / Drug Compounding / Drug Liberation / Evaporation / Hexoses - chemistry / HIV Protease Inhibitors - chemistry / Infrared spectroscopy / Kinetics / Light scattering / Mandatory drug testing / Medical Law / Pharmacology/Toxicology / Pharmacy / Physicochemical properties / Polyethylene glycol / Polymers / Polyols / Polysorbates - chemistry / Pyrrolidines - chemistry / Research Paper / Ritonavir / Ritonavir - chemistry / Scanning electron microscopy / Sodium lauryl sulfate / Solubility / Sulfates / Surface active agents / Surface-Active Agents - chemistry / Surfactants / Vinyl Compounds - chemistry / Vitamin E - chemistry