title: Drug loading into beta-cyclodextrin granules using a supercritical fluid process for improved drug dissolution.
abstract: To improve dissolution properties of drugs, a supercritical fluid (SCF) technique was used to load these drugs into a solid carrier. In this study, granules based on beta-cyclodextrin (betaCD) were applied as a carrier for poor water-soluble drug and loaded with a model drug (ibuprofen) using two different procedures: controlled particle deposition (CPD), SCF process and solution immersion (SI) as a conventional method for comparison. Using the CPD technique, 17.42+/-2.06wt.% (n=3) ibuprofen was loaded into betaCD-granules, in contrast to only 3.8+/-0.15wt.% (n=3) in the SI-product. The drug loading was confirmed as well by reduction of the BET surface area for the CPD-product (1.134+/-0.07m(2)/g) compared to the unloaded-granules (1.533+/-0.031m(2)/g). Such a reduction was not seen in the SI-product (1.407+/-0.048m(2)/g). The appearance of an endothermic melting peak at 77 degrees C and X-ray patterns representing ibuprofen in drug-loaded granules can be attributed to the amount of ibuprofen loaded in its crystalline form. A significant increase in drug dissolution was achieved by either drug-loading procedures compared to the unprocessed ibuprofen. In this study, the CPD technique, a supercritical fluid process avoiding the use of toxic or organic solvents was successfully applied to load drug into solid carriers, thereby improving the water-solubility of the drug.
authors.affiliation: Pharmazeutische Technologie, Eberhard-Karls-Universität Tübingen, Auf der Morgenstelle 8, D-72076 Tübingen, Germany.
authors.forename: Khaled
authors.initials: K
authors.lastname: Hussein
authors.forename: Michael
authors.initials: M
authors.lastname: Türk
authors.forename: Martin A
authors.initials: MA
authors.lastname: Wahl
mesh_terms: D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000737:chemistry; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods*; D007052:Ibuprofen / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D047392:beta-Cyclodextrins; D002482:Cellulose; D011205:Povidone; C031215:betadex; C109691:microcrystalline cellulose; D007052:Ibuprofen