title: Enhancement of docetaxel solubility using binary and ternary solid dispersion systems.
abstract: BACKGROUND
  Poor biopharmaceutical properties and toxicities associated with the intravenous formulation of docetaxel (DTX) necessitate the exploration of an alternate oral route of delivery.
  
  
  OBJECTIVE
  This study aims at enhancing the solubility of poorly soluble drug, DTX with the help of solid dispersion (SD) technique.
  
  
  METHODS
  DTX SDs were formulated with selected solubilizers, including Kollidon 12PF, Lutrol F68, Soluplus and Hydroxypropyl-β-cyclodextrin in different weight ratios. Freeze-drying method was used to prepare the binary and ternary SDs. Kinetic solubility of the SDs was evaluated in order to select best DTX-solubilizer combination. Best performing combination was then characterized using differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM).
  
  
  CONCLUSIONS
  Among all SDs tested, Soluplus outperformed all the excipients at equivalent weight ratio. Binary SD of DTX and Soluplus (1:10) resulted in the highest improvement in solubility (362.93 ± 11.01 µg/mL). This is approximately a 93-fold increment as compared to the solubility of crystalline DTX (3.9 ± 0.2 µg/mL). This exceptional performance can be attributed to solid-state transformation as well as micellization.
  
  
  CONCLUSIONS
  Among all the excipients tested, Soluplus dispersion is the most promising candidate for oral formulation development.
authors.affiliation: a International Medical University , Kuala Lumpur , Malaysia and.
authors.forename: Sue May
authors.initials: SM
authors.lastname: Lim
authors.affiliation: a International Medical University , Kuala Lumpur , Malaysia and.
authors.forename: Zyu Wenn
authors.initials: ZW
authors.lastname: Pang
authors.affiliation: a International Medical University , Kuala Lumpur , Malaysia and.
authors.forename: Hwei Yuin
authors.initials: HY
authors.lastname: Tan
authors.affiliation: b Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia , Adelaide , SA , Australia.
authors.forename: Mohsin
authors.initials: M
authors.lastname: Shaikh
authors.affiliation: a International Medical University , Kuala Lumpur , Malaysia and.
authors.forename: Gorajana
authors.initials: G
authors.lastname: Adinarayana
authors.affiliation: b Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia , Adelaide , SA , Australia.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Garg
mesh_terms: D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D000077143:Docetaxel; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying; D008855:Microscopy, Electron, Scanning; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D005079:Excipients; D011145:Polyvinyls; D043823:Taxoids; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D000077143:Docetaxel; D011092:Polyethylene Glycols
keywords: Anti-cancer; Soluplus; apparent solubility; freeze-drying; solubility parameter