Improvement of the dissolution rate of artemisinin by means of supercritical fluid technology and solid dispersions.
The purpose of this study was to enhance the dissolution rate of artemisinin in order to improve the intestinal absorption characteristics. The effect of: (1) micronisation and (2) formation of solid dispersions with PVPK25 was assessed in an in vitro dissolution system [dissolution medium: water (90%), ethanol (10%) and sodium lauryl sulphate (0.1%)]. Coulter counter analysis was used to measure particle size. X-ray diffraction and DSC were used to analyse the physical state of the powders. Micronisation by means of a jet mill and supercritical fluid technology resulted in a significant decrease in particle size as compared to untreated artemisinin. All powders appeared to be crystalline. The dissolution rate of the micronised forms improved in comparison to the untreated form, but showed no difference in comparison to mechanically ground artemisinin. Solid dispersions of artemisinin with PVPK25 as a carrier were prepared by the solvent method. Both X-ray diffraction and DSC showed that the amorphous state was reached when the amount of PVPK25 was increased to 67%. The dissolution rate of solid dispersions with at least 67% of PVPK25 was significantly improved in comparison to untreated and mechanically ground artemisinin. Modulation of the dissolution rate of artemisinin was obtained by both particle size reduction and formation of solid dispersions. The effect of particle size reduction on the dissolution rate was limited. Solid dispersions could be prepared by using a relatively small amount of PVPK25. The formation of solid dispersions with PVPK25 as a carrier appears to be a promising method to improve the intestinal absorption characteristics of artemisinin.
Van Nijlen
T
T
Laboratorium voor Farmacotechnologie en Biofarmacie, O&N, Gasthuisberg, KU Leuven, B-3000 Leuven, Belgium.
Brennan
K
K
Van den Mooter
G
G
Blaton
N
N
Kinget
R
R
Augustijns
P
P
D000962:Antimalarials / Q000737:chemistry*; D037621:Artemisinins / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004337:Drug Carriers; D010316:Particle Size; D011205:Povidone / Q000737:chemistry; D011208:Powders; D012717:Sesquiterpenes / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical; D014961:X-Ray Diffraction
D000962:Antimalarials; D037621:Artemisinins; D004337:Drug Carriers; D011208:Powders; D012717:Sesquiterpenes; C031327:artemisinin; D011205:Povidone