Comparison of Two Grafted Copolymers, Soluplus and Kollicoat IR, as Solid Dispersion Carriers of Arteether for Oral Delivery Prepared by Different Solvent-Based Methods

Abstract

Arteether (ART), an antimalarial drug, belongs to BCS class II and has very low oral bioavailability. Clinically, it is given as a solution in oil by the intramuscular route. Solid dispersion in Soluplus or Kollicoat IR, two commonly used grafted copolymers, may improve its in vitro dissolution and oral bioavailability. ART solid dispersion was prepared by three solvent-based methods: rotary evaporation (ethanol as solvent), spray drying (hydro-alcoholic solvent), and freeze-drying (aqueous solvent). ART-polymer miscibility increases with increasing polymeric concentrations up to 4% or 6%. Spray drying resulted in the highest increment of ART saturation solubility (476.01 ± 10.01 mg/L) than that of rotary evaporation (432.22 ± 15.76 mg/L) or freeze-drying (122.97 ± 2.94 mg/L) in the drug-Soluplus (1:1 w/w) ratio. Also, with Kollicoat IR-based solid dispersion, the same trend was observed. The drug-polymer ratio of 1:3 (w/w) showed a decrease in saturation solubility. Spray-dried products were better for flow properties (Carr index: 21.27 ± 0.98 for the 1:1 ratio of drug-Soluplus solid dispersion) than the other two methods. An enteric-coated capsule was prepared with an ART-Soluplus (1:1) ratio, selected based on the saturation solubility and downstream feasibility compared with those of Kollicoat IR. Eudragit L-100-coated enteric capsules containing 100 mg equivalent ART showed 88.88 ± 2.9% drug release in phosphate buffer pH 6.8 medium, which is significantly higher than that in raw drug (<10%) and a physical mixture of the exact composition of solid dispersion (44%). The study concluded that Soluplus possesses better properties as a solid dispersion carrier than those of Kollicoat IR. A stable, partially amorphous solid dispersion of ART was developed that can provide improved oral bioavailability.