In vitro release and stability of an artesunate rectal gel suitable for pediatric use.

Abstract The rectal route is indicated to treat patients with rapidly evolving malaria who cannot take oral medication to prevent progression to severe forms of the disease. Improvement can be made in terms of rectal bioavailability and stability of current formulations. We studied a new two-compartment, muco-adhesive gel formulation of artesunate which is adapted for use in children and storage in tropical climates. The formulation contains 50 mg of artesunate per gram of gel. Because of its instability in aqueous solutions, artesunate is in the dry component of the gel with Carbopol ® and separate from the liquid phase until reconstitution. Artesunate is stable in the dry blend for 6 months at 45 °C and 60% RH. The gel should be used between 1 and 72 h after being reconstituted. Artesunate release was measured by with a rapid, simple and reliable HPLC-UV which allowed the analysis of artesunate and dihydroartemisinin with an analysis time at 3 min. The amount of artesunate released over 6 h was 56 ± 0.97%. Compared to the reference suspension, total release and dissolution efficiency were lower and rate of release was slower (time to 50% dissolution 271 ± 21 min), probably because of the higher viscosity of the gel, but the drug release profiles were similar. The calculated in vitro release exponent ( n ) value suggested that artesunate is released from the gel by non-Fickian transport.