title: Optimization of a PGSS (particles from gas saturated solutions) process for a fenofibrate lipid-based solid dispersion formulation.
abstract: The aim of this study was to develop a formulation containing fenofibrate and Gelucire(®) 50/13 (Gattefossé, France) in order to improve the oral bioavailability of the drug. Particles from gas saturated solutions (PGSS) process was chosen for investigation as a manufacturing process for producing a solid dispersion. The PGSS process was optimized according to the in vitro drug dissolution profile obtained using a biphasic dissolution test. Using a design of experiments approach, the effects of nine experimental parameters were investigated using a PGSS apparatus provided by Separex(®) (Champigneulles, France). Within the chosen experimental conditions, the screening results showed that the drug loading level, the autoclave temperature and pressure, the connection temperature and the nozzle diameter had a significant influence on the dissolution profile of fenofibrate. During the optimization step, the three most relevant parameters were optimized using a central composite design, while other factors remained fixed. In this way, we were able to identify the optimal production conditions that would deliver the highest level of fenofibrate in the organic phase at the end of the dissolution test. The closeness between the measured and the predicted optimal dissolution profiles in the organic phase demonstrated the validity of the statistical analyses.
authors: Laboratory of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, C.I.R.M., University of Liège, CHU, Tour 4, 2nd floor, 4000 Liège, Belgium. Electronic address: Aude.Pestieau@ulg.ac.be.
authors: Aude
authors: A
authors: Pestieau
authors: Laboratory of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, C.I.R.M., University of Liège, CHU, Tour 4, 2nd floor, 4000 Liège, Belgium.
authors: Fabrice
authors: F
authors: Krier
authors: Arlenda s.a., 4000 Liège, Belgium.
authors: Pierre
authors: P
authors: Lebrun
authors: Galéphar Research Center M/F, rue du Parc Industriel 39, 6900 Marche-en-Famenne, Belgium.
authors: Adeline
authors: A
authors: Brouwers
authors: Galéphar Research Center M/F, rue du Parc Industriel 39, 6900 Marche-en-Famenne, Belgium.
authors: Bruno
authors: B
authors: Streel
authors: Laboratory of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, C.I.R.M., University of Liège, CHU, Tour 4, 2nd floor, 4000 Liège, Belgium.
authors: Brigitte
authors: B
authors: Evrard
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D002245:Carbon Dioxide / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004867:Equipment Design; D005223:Fats / Q000737:chemistry*; D011345:Fenofibrate / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D005740:Gases; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008956:Models, Chemical; D015233:Models, Statistical; D009821:Oils / Q000737:chemistry*; D011312:Pressure; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D013696:Temperature
chemical_list: D004337:Drug Carriers; D005223:Fats; D005740:Gases; D000960:Hypolipidemic Agents; D009821:Oils; C071184:Gelucire 50-13; D002245:Carbon Dioxide; D011345:Fenofibrate
keywords: Acetonitrile (PubChem CID: 6342); Biphasic dissolution test; Carbon dioxide (PubChem CID: 280); Design of experiments; Dimethyl sulfoxide (PubChem CID: 679); Fenofibrate; Fenofibrate (PubChem CID: 3339); Hydrochloric acid (PubChem CID: 313); Octanol (PubChem CID: 957); Particles from gas saturated solutions; Solid dispersion; Supercritical carbon dioxide; Water (PubChem CID: 962)