title: New Perspectives for Fixed Dose Combinations of Poorly Water-Soluble Compounds: a Case Study with Ezetimibe and Lovastatin.
abstract: OBJECTIVE
  Aiming to improve the dissolution rate of ezetimibe (EZE) and lovastatin (LOV) in a fixed dose combination (FDC), co-amorphous systems and ternary solid dispersions were prepared by quench cooling and spray drying, respectively.
  
  
  METHODS
  Formulations were characterized through X-ray diffraction, modulated differential scanning calorimetry, infrared spectroscopy, scanning electron microscopy and laser diffraction, and evaluated by 'in vitro' dissolution. Stability studies were conducted at different conditions during 30 days with the ternary solid dispersion composed of 75% of Soluplus® (ELS 1:1 75%).
  
  
  RESULTS
  Single phase co-amorphous systems made up of the pure drugs were not able to increase the dissolution rate of EZE and LOV. However, ternary solid dispersions achieved high dissolution for both compounds, especially when Soluplus® was used as carrier. The dissolution efficiency increased up to 18 (EZE) and 6 (LOV) times in ternary solid dispersions, compared to the crystalline drugs. ELS 1:1 75% preserved its amorphous state during 30 days, in different stability conditions.
  
  
  CONCLUSIONS
  A spray dried ternary solid dispersion able to enhance the dissolution rate of two poorly soluble, therapeutically complementary drugs, is reported for the first time. These promising results open new perspectives for the development of more advanced FDCs.
authors: Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, KU Leuven, Campus Gasthuisberg ON2, Herestraat 49 b921, 3000, Leuven, Belgium.|Laboratório de Controle de Qualidade, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Campus Reitor João David Ferreira Lima, Trindade, 88040-970, Florianópolis, SC, Brazil.
authors: Manoela K
authors: MK
authors: Riekes
authors: Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, KU Leuven, Campus Gasthuisberg ON2, Herestraat 49 b921, 3000, Leuven, Belgium.
authors: Axel
authors: A
authors: Engelen
authors: Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, KU Leuven, Campus Gasthuisberg ON2, Herestraat 49 b921, 3000, Leuven, Belgium.
authors: Bernard
authors: B
authors: Appeltans
authors: Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, KU Leuven, Campus Gasthuisberg ON2, Herestraat 49 b921, 3000, Leuven, Belgium.
authors: Patrick
authors: P
authors: Rombaut
authors: Laboratório de Controle de Qualidade, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Campus Reitor João David Ferreira Lima, Trindade, 88040-970, Florianópolis, SC, Brazil.
authors: Hellen K
authors: HK
authors: Stulzer
authors: Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, KU Leuven, Campus Gasthuisberg ON2, Herestraat 49 b921, 3000, Leuven, Belgium. guy.vandenmooter@pharm.kuleuven.be.
authors: Guy
authors: G
authors: Van den Mooter
mesh_terms: D000924:Anticholesteremic Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D003890:Desiccation; D004338:Drug Combinations; D004339:Drug Compounding; D004355:Drug Stability; D000069438:Ezetimibe / Q000737:chemistry*; D008148:Lovastatin / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D000924:Anticholesteremic Agents; D004338:Drug Combinations; D014867:Water; D008148:Lovastatin; D000069438:Ezetimibe
keywords: co-amorphous systems; ezetimibe; fixed dose combinations; lovastatin; ternary solid dispersions