title: Development of a solid self-microemulsifying drug delivery system (SMEDDS) for solubility enhancement of naproxen.
abstract: BACKGROUND
  Comparative evaluation of liquid and solid self-microemulsifying drug delivery systems (SMEDDS) as promising approaches for solubility enhancement.
  
  
  OBJECTIVE
  The aim of this work was to develop, characterize, and evaluate a solid SMEDDS prepared via spray-drying of a liquid SMEDDS based on Gelucire® 44/14 to improve the solubility and dissolution rate of naproxen.
  
  
  METHODS
  Various oils and co-surfactants in combination with Gelucire® 44/14 were evaluated during excipient selection study, solubility testing, and construction of (pseudo)ternary diagrams. The selected system was further evaluated for naproxen solubility, self-microemulsification ability, and in vitro dissolution of naproxen. In addition, its transformation into a solid SMEDDS by spray-drying using maltodextrin as a solid carrier was performed. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to evaluate the physical characteristics of the solid SMEDDS obtained.
  
  
  RESULTS
  The selected formulation of SMEDDS was comprised of Miglyol 812®, Peceol™, Gelucire® 44/14, and Solutol® HS 15. The liquid and solid SMEDDS formed a microemulsion after dilution with comparable average droplet size and exhibited uniform droplet size distribution. In the solid SMEDDS, liquid SMEDDS was adsorbed onto the surface of maltodextrin and formed smooth granular particles with the encapsulated drug predominantly in a dissolved state and partially in an amorphous state. Overall, incorporation of naproxen in SMEDDS, either liquid or solid, resulted in improved solubility and dissolution rate compared to pure naproxen.
  
  
  CONCLUSIONS
  This study indicates that a liquid and solid SMEDDS is a strategy for solubility enhancement in the future development of orally delivered dosage forms.
authors.affiliation: a Krka, d.d., Novo mesto , Novo Mesto , Slovenia and.
authors.forename: Katja
authors.initials: K
authors.lastname: Čerpnjak
authors.forename: Alenka
authors.initials: A
authors.lastname: Zvonar
authors.forename: Franc
authors.initials: F
authors.lastname: Vrečer
authors.forename: Mirjana
authors.initials: M
authors.lastname: Gašperlin
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D009288:Naproxen / Q000008:administration & dosage* / Q000737:chemistry; D009821:Oils / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004655:Emulsions; D005079:Excipients; D009821:Oils; D013501:Surface-Active Agents; C104509:gelucire 44-14; D011092:Polyethylene Glycols; D009288:Naproxen
keywords: Crystalline properties; dissolution; microemulsion; self-microemulsifying; spray-drying