title: Characterization of Amorphous and Co-Amorphous Simvastatin Formulations Prepared by Spray Drying.
abstract: In this study, spray drying from aqueous solutions, using the surface-active agent sodium lauryl sulfate (SLS) as a solubilizer, was explored as a production method for co-amorphous simvastatin-lysine (SVS-LYS) at 1:1 molar mixtures, which previously have been observed to form a co-amorphous mixture upon ball milling. In addition, a spray-dried formulation of SVS without LYS was prepared. Energy-dispersive X-ray spectroscopy (EDS) revealed that SLS coated the SVS and SVS-LYS particles upon spray drying. X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) showed that in the spray-dried formulations the remaining crystallinity originated from SLS only. The best dissolution properties and a "spring and parachute" effect were found for SVS spray-dried from a 5% SLS solution without LYS. Despite the presence of at least partially crystalline SLS in the mixtures, all the studied formulations were able to significantly extend the stability of amorphous SVS compared to previous co-amorphous formulations of SVS. The best stability (at least 12 months in dry conditions) was observed when SLS was spray-dried with SVS (and LYS). In conclusion, spray drying of SVS and LYS from aqueous surfactant solutions was able to produce formulations with improved physical stability for amorphous SVS.
authors.affiliation: School of Pharmacy, University of Eastern Finland, Yliopistonranta 1C, Kuopio FI-70210, Finland. goedele.craye@ugent.be.|Department of Pharmaceutical Analysis, University of Ghent, Harelbekestraat 72, Ghent B-9000, Belgium. goedele.craye@ugent.be.
authors.forename: Goedele
authors.initials: G
authors.lastname: Craye
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, Copenhagen DK-2100, Denmark. korbinian.loebmann@sund.ku.dk.
authors.forename: Korbinian
authors.initials: K
authors.lastname: Löbmann
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, Copenhagen DK-2100, Denmark. holger.grohganz@sund.ku.dk.
authors.forename: Holger
authors.initials: H
authors.lastname: Grohganz
authors.affiliation: Department of Pharmacy, University of Copenhagen, Universitetsparken 2, Copenhagen DK-2100, Denmark. thomas.rades@sund.ku.dk.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.affiliation: School of Pharmacy, University of Eastern Finland, Yliopistonranta 1C, Kuopio FI-70210, Finland. riikka.laitinen@uef.fi.
authors.forename: Riikka
authors.initials: R
authors.lastname: Laitinen
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003890:Desiccation; D004339:Drug Compounding; D016503:Drug Delivery Systems; D019821:Simvastatin / Q000008:administration & dosage / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000924:Anticholesteremic Agents; D013501:Surface-Active Agents; D019821:Simvastatin
keywords: co-amorphous; dissolution; energy-dispersive X-ray spectroscopy; solubility; spray drying; stability