title: Formulation and delivery of improved amorphous fenofibrate solid dispersions prepared by thin film freezing.
abstract: The objective of this study was to prepare amorphous fenofibrate (FB) solid dispersions using thin film freezing (TFF) and to incorporate the solid dispersions into pharmaceutically acceptable dosage forms. FB solid dispersions prepared with optimized drug/polymer ratios were characterized by modulated differential scanning calorimetry (MDSC), powder X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) specific surface area measurements, Fourier-transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), and supersaturation dissolution testing. Furthermore, a dry granulation technique was used to encapsulate the TFF compositions for in vitro dissolution and in vivo animal pharmacokinetic studies. The results showed that the TFF process produced amorphous, porous, microstructured, and stable solid dispersions with high surface areas. Development of solid oral dosage forms revealed that the performance of the FB containing solid dispersions was not affected by the formulation process, which was confirmed by DSC and XRD. Moreover, an in vivo pharmacokinetic study in rats revealed a significant increase in FB absorption compared to bulk FB. We confirmed that amorphous solid dispersions with large surface areas produced by the TFF process displayed superior dissolution rates and corresponding enhanced bioavailability of the poorly water-soluble drug, FB.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Meimei
authors.initials: M
authors.lastname: Zhang
authors.forename: Houli
authors.initials: H
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Lang
authors.forename: Kevin
authors.initials: K
authors.lastname: O'Donnell
authors.forename: Haohao
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhouhua
authors.initials: Z
authors.lastname: Wang
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Dong
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Wu
authors.forename: Robert O
authors.initials: RO
authors.lastname: Williams
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D016503:Drug Delivery Systems; D011345:Fenofibrate / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005615:Freezing; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008855:Microscopy, Electron, Scanning; D016062:Porosity; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D000960:Hypolipidemic Agents; D011345:Fenofibrate