Title:Development of Hot Melt Extruded Co-Formulated Artesunate and Amodiaquine- Soluplus® Solid Dispersion System in Fixed-Dose Form: Amorphous State Characterization and Pharmacokinetic Evaluation
Volume: 25
Issue: 7
Author(s): Md Ali Mujtaba, Ritesh Fule*, Purnima Amin, Gamal Osman Elhassan, Meshal Meteab Majed Almoutairi, Mohammed Kaleem and Musarrat Husain Warsi
Affiliation:
- Department of Pharmaceutics
& Quality Assurance, Dadasaheb Balpande College of Pharmacy, Besa, Nagpur, 440037, Maharashtra, India
Keywords:
Hot melt extrusion, solid dispersion, solubility, dissolution, solid state, pharmacokinetic.
Abstract:
Introduction: This study aims to develop co-amorphous Solid Dispersion (SD) system containing
antimalarials Artesunate (ARS) and Amodiaquine (AMQ) to improve its oral bioavailability employing the
Hot Melt Extrusion (HME) technique. Soluplus® was selected as a polymeric excipient, whereas Lutrol F127,
Lutrol F68, TPGS, and PEG400 as surfactants were incorporated along with Soluplus® to enhance extrudability,
improve hydrophilicity, and improve the blend viscosity during HME. Soluplus® with surfactant combination
successfully stabilizes both drugs during extrusion by generating SD because of its lower glass transition
temperature (Tg) and viscoelastic behavior
Methods: Physicochemical characterizations were performed using FTIR, DSC, TGA, and XRD, which confirmed
the amorphousization of drugs in the SD system. The molecular level morphology of the optimized
formulation was quantified using high-resolution techniques such as Atomic-Force Microscopy (AFM), Raman
spectral, and mapping analysis. The transition of the crystalline drugs into a stable amorphous form has
been demonstrated by 1H-NMR and 2D-NMR studies. The in vivo pharmacokinetics study in rats showed that
the SD-containing drug-Soluplus-TPGS (FDC10) formulation has 36.63-56.13 (ARS-AMQ) folds increase in
the Cmax and 41.87-54.34 (ARS-AMQ) folds increase AUC (0–72) as compared to pure drugs.
Results: Pharmacokinetic analysis shows that a fixed-dose combination of 50:135 mg of both APIs (ARSAMQ)
significantly increased oral bioavailability by elevating Cmax and AUC, in comparison to pure APIs
and also better than the marketed product Coarsucam®.
Conclusion: Therefore, the developed melt extruded co-amorphous formulation has enhanced bioavailability
and has more effectiveness than the marketed product Coarsucam®.
.
