Sustained-release Liquisolid Compacts of Lumenfantrine-Artemether as Alternate-Day-Regimen for Malaria Treatment to Improve Patient Compliance

摘要

Lumenfantrine SLNs (LUM-SLNs, 0.2, 0.5, 0.8 and 1%w/w) were formulated with Precirol-Transcutol (PT) and Tallow fat-Transcutol (TT) at 3:1 ratios using Poloxamer 188, Polysorbate 80 and Solutol HS by hot homogenization. Thermal properties, particle size/morphology, ZP, PDI, EE, interaction study and in vitro drug release were carried out. LUM-SLNs were directly compressed with artemether into liquisolid compacts (AL). In-vitro release was done in biorelevant media. Peter's 4-day curative test was done in CQ-sensitive strain of Plasmodium berghei berghei. Nanoparticles were formed with high % yield, stability (-24.8 to-29.2), low enthalpy and high EE (70-95 %). Liquisolid compacts sustained LUM release in SIF (84.32%, PT-SLN) better than (77.9%, SLN-TT). Non-Fickian (anomalous) diffusion and super case II transport were predominant mechanisms. Equal parasitaemia reduction was seen for all particles (～92%) superior to 86% from Coartem and 66% commercial CQ-PO_4. No significant difference (p<0.05) between double (4/24 mg/kg) and single (2/12 mg/kg) strength doses of artemether-lumenfantrine (AL) compacts was seen. AL could be formulated in lower doses (4/24 mg/kg) and taken orally once-in-two days to improve patient compliance which is currently problematic with conventional forms containing 20/120 mg of AL and taken for 6 doses, in addition to erratic absorption and numerous side effects due to large doses.