Effect of the solid-dispersion method on the solubility and crystalline property of tacrolimus.
Three solid dispersions containing poorly water-soluble tacrolimus were prepared with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and dioctyl sulfosuccinate (DOSS) using a spray-drying technique via the solvent-evaporation method with a methylene chloride/ethanol mixture, the solvent-wetting method with ethanol and the surface-attached method with water, respectively. The solubility and dissolution of the drug in the three solid dispersions were evaluated compared to drug powder. Furthermore, their physicochemical properties were investigated using SEM, DSC and powder X-ray diffraction. The solubility and dissolution of the drug were significantly improved in the order of the tacrolimus-loaded solid dispersion prepared by: solvent-evaporation method>solvent-wetting method>surface-attached method. The solid dispersions prepared by solvent evaporation appeared as an aggregated form with the amorphous form. In particular, the solid dispersion prepared by the solvent-evaporation method improved solubility about 900-fold and dissolution of tacrolimus 15-fold because of its reduced particle size, increased surface area and close contact between the hydrophilic carrier and the drug. In the solvent-wetting method, the drug, which was changed to an amorphous form, was attached onto the surface of undissolved carriers. However, the solid dispersion prepared by the surface-attached method gave an unchanged crystalline form. In this solid dispersion, the carriers were attached to the surface of the undissolved drug, resulting in changing the drug from being hydrophobic to hydrophilic. As the crystal form of drug in this solid dispersion was not converted to the amorphous form unlike other solid dispersions, it gave relatively less solubility and dissolution of the drug than did the others. Thus, in the development of a solid-dispersion system containing poorly water-soluble drugs, the method of preparation plays an important role in the solubility and crystallinity of the drugs.
Joe
Jung Hyun
JH
College of Pharmacy, Yeungnam University, 214-1 Dae-Dong, Gyongsan 712-749, South Korea.
Lee
Won Mo
WM
Park
Young-Joon
YJ
Joe
Kwan Hyung
KH
Oh
Dong Hoon
DH
Seo
Youn Gee
YG
Woo
Jong Soo
JS
Yong
Chul Soon
CS
Choi
Han-Gon
HG
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D004143:Dioctyl Sulfosuccinic Acid / Q000737:chemistry; D004337:Drug Carriers; D004339:Drug Compounding; D000431:Ethanol / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007166:Immunosuppressive Agents / Q000737:chemistry*; D007700:Kinetics; D008752:Methylene Chloride / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D033362:Powder Diffraction; D011208:Powders; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D016559:Tacrolimus / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry
D004337:Drug Carriers; D007166:Immunosuppressive Agents; D011208:Powders; D012997:Solvents; D047392:beta-Cyclodextrins; D014867:Water; D004143:Dioctyl Sulfosuccinic Acid; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000431:Ethanol; D008752:Methylene Chloride; D016559:Tacrolimus