title: Development and optimization of a new processing approach for manufacturing topical liposomes-in-hydrogel drug formulations by dual asymmetric centrifugation.
abstract: OBJECTIVE
  The objective of the present study was to utilize dual asymmetric centrifugation (DAC) as a novel processing approach for the production of liposomes-in-hydrogel formulations.
  
  
  METHODS
  Lipid films of phosphatidylcholine, with and without chloramphenicol (CAM), were hydrated and homogenized by DAC to produce liposomes in the form of vesicular phospholipid gels with a diameter in the size range of 200-300 nm suitable for drug delivery to the skin. Different homogenization processing parameters were investigated along with the effect of adding propylene glycol (PG) to the formulations prior to homogenization. The produced liposomes were incorporated into a hydrogel made of 2.5% (v/v) soluble β-1,3/1,6-glucan (SBG) and mixed by DAC to achieve a homogenous liposomes-in-hydrogel-formulation suitable for topical application.
  
  
  CONCLUSIONS
  CAM-containing liposomes with a vesicle diameter of 282 ± 30 nm and polydispersity index (PI) of 0.13 ± 0.02 were successfully produced by DAC after 50 min centrifugation at 3500 rpm, and homogenously (< 4% content variation) incorporated into the SBG hydrogel. Addition of PG decreased the necessary centrifugation time to 2 min and 55 s, producing liposomes of 230 ± 51 nm and PI of 0.25 ± 0.04. All formulations had an entrapment efficiency of approximately 50%.
  
  
  CONCLUSIONS
  We managed to develop a relatively fast and reproducible new method for the production of liposomes-in-hydrogel formulations by DAC.
authors.affiliation: a Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences , University of Tromsø the Arctic University of Norway , Tromsø , Norway.
authors.forename: Sveinung G
authors.initials: SG
authors.lastname: Ingebrigtsen
authors.affiliation: a Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences , University of Tromsø the Arctic University of Norway , Tromsø , Norway.
authors.forename: Nataša
authors.initials: N
authors.lastname: Škalko-Basnet
authors.affiliation: a Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences , University of Tromsø the Arctic University of Norway , Tromsø , Norway.
authors.forename: Ann Mari
authors.initials: AM
authors.lastname: Holsæter
mesh_terms: D000287:Administration, Topical; D002498:Centrifugation / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002701:Chloramphenicol / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D005782:Gels / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D010316:Particle Size; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D019946:Propylene Glycol / Q000737:chemistry; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D005782:Gels; D008055:Lipids; D008081:Liposomes; D010713:Phosphatidylcholines; D010743:Phospholipids; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D002701:Chloramphenicol; D019946:Propylene Glycol
keywords: Chloramphenicol; dual asymmetric centrifugation; hydrogels; liposomes; skin therapy; soluble beta-glucan