title: Agglomerated oral dosage forms of artemisinin/β-cyclodextrin spray-dried primary microparticles showing increased dissolution rate and bioavailability.
abstract: Artemisinin, a poorly water-soluble antimalarial drug, presents a low and erratic bioavailability upon oral administration. The aim of this work was to study an agglomerated powder dosage form for oral administration of artemisinin based on the artemisinin/β-cyclodextrin primary microparticles. These primary microparticles were prepared by spray-drying a water-methanol solution of artemisinin/β-cyclodextrin. β-Cyclodextrin in spray-dried microparticles increased artemisinin water apparent solubility approximately sixfold. The thermal analysis evidenced a reduction in the enthalpy value associated with drug melting, due to the decrease in drug crystallinity. The latter was also evidenced by powder X-ray diffraction analysis, while (13)C-NMR analysis indicated the partial complexation with β-cyclodextrin. Agglomerates obtained by sieve vibration of spray-dried artemisinin/β-cyclodextrin primary microparticles exhibited free flowing and close packing properties compared with the non-flowing microparticulate powder. The in vitro dissolution rate determination of artemisinin from the agglomerates showed that in 10 min about 70% of drug was released from the agglomerates, whereas less than 10% of artemisinin was dissolved from raw material powder. Oral administration of agglomerates in rats yielded higher artemisinin plasma levels compared to those of pure drug. In the case of the agglomerated powder, a 3.2-fold increase in drug fraction absorbed was obtained.
authors.affiliation: Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124, Parma, Italy.
authors.forename: Anna Giulia
authors.initials: AG
authors.lastname: Balducci
authors.forename: Enrico
authors.initials: E
authors.lastname: Magosso
authors.forename: Gaia
authors.initials: G
authors.lastname: Colombo
authors.forename: Fabio
authors.initials: F
authors.lastname: Sonvico
authors.forename: Nurzalina Abdul Karim
authors.initials: NA
authors.lastname: Khan
authors.forename: Kah Hay
authors.initials: KH
authors.lastname: Yuen
authors.forename: Ruggero
authors.initials: R
authors.lastname: Bettini
authors.forename: Paolo
authors.initials: P
authors.lastname: Colombo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rossi
mesh_terms: D000284:Administration, Oral; D037621:Artemisinins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D004304:Dosage Forms; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics; D047392:beta-Cyclodextrins / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D037621:Artemisinins; D004304:Dosage Forms; D047392:beta-Cyclodextrins; C031327:artemisinin; C031215:betadex