Melt extrusion--an alternative method for enhancing the dissolution rate of 17beta-estradiol hemihydrate.
17Beta-estradiol hemihydrate (17beta-E2) is a poorly water-soluble drug. Physical methods for improving the solubility and dissolution rate, e.g. micronization, have certain inherent disadvantages. The method of choice in this study, melt extrusion, proved to overcome many of the shortcomings of conventional methods. Different compositions of excipients such as PEG 6000, PVP (Kollidon 30) or a vinylpyrrolidone-vinylacetate-copolymer (Kollidon VA64) were used as polymers and Sucroester WE15 or Gelucire 44/14 as additives during melt extrusion. The solid dispersions resulted in a significant increase in dissolution rate when compared to the pure drug or to the physical mixtures. For example, a 30-fold increase in dissolution rate was obtained for a formulation containing 10% 17beta-E2, 50% PVP and 40% Gelucire 44/14. The solid dispersions were then processed into tablets. The improvement in the dissolution behavior was also maintained with the tablets. The USP XXIII requirement for estradiol tablets reaching greater than 75% drug dissolved after 60 min was obtained in this investigation.
Hülsmann
S
S
Pharmaceutical Development/Oral Dosage Forms, Schering AG, Berlin, Germany. stefan.huelsmann@schering.de
Backensfeld
T
T
Keitel
S
S
Bodmeier
R
R
D004339:Drug Compounding / Q000379:methods*; D004958:Estradiol / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D012995:Solubility; D012996:Solutions; D012997:Solvents; D013607:Tablets; D014961:X-Ray Diffraction
D012996:Solutions; D012997:Solvents; D013607:Tablets; D004958:Estradiol