title: Liposomal hydrogel formulation for transdermal delivery of pirfenidone.
abstract: BACKGROUND
  Pirfenidone (PFD) is an anti-fibrotic and anti-inflammatory agent indicated for the treatment of idiopathic pulmonary fibrosis (IPF). The current oral administration of PFD has several limitations including first pass metabolism and gastrointestinal irritation.
  
  
  OBJECTIVE
  The aim of this study is to investigate the feasibility of transdermal delivery of PFD using liposomal carrier system.
  
  
  METHODS
  PFD-loaded liposomes were prepared using soy phosphatidylcholine (SPC) and sodium cholate (SC). Encapsulation efficiency (EE) of PFD in liposomes was optimized using different preparation techniques including thin film hydration (TFH) method, direct injection method (DIM) and drug encapsulation using freeze-thaw cycles. In vitro drug release study was performed using dialysis membrane method. The skin permeation studies were performed using excised porcine ear skin model in a Franz diffusion cell apparatus.
  
  
  CONCLUSIONS
  The average particle size and zeta-potential of liposomes were 191 ± 4.1 nm and -40.4 ± 4.5 mV, respectively. The liposomes prepared by TFH followed by 10 freeze-thaw cycles showed the greatest EE of 22.7 ± 0.63%. The optimized liposome formulation was incorporated in hydroxypropyl methyl cellulose (HPMC) hydrogel containing different permeation enhancers including oleic acid (OA), isopropyl myristate (IPM) and propylene glycol (PG). PFD-loaded liposomes incorporated in hydrogel containing OA and IPM showed the greatest flux of 10.9 ± 1.04 μg/cm(2)/h across skin, which was 5-fold greater compared with free PFD. The cumulative amount of PFD permeated was 344 ± 28.8 μg/cm(2) with a lag time of 2.3 ± 1.3 h.
  
  
  CONCLUSIONS
  The hydrogel formulation containing PFD-loaded liposomes can be developed as a potential transdermal delivery system.
authors.affiliation: a Department of Pharmacy , Birla Institute of Technology and Science (BITS) Pilani , Hyderabad Campus , Hyderabad , Telangana , India.
authors.forename: Anup
authors.initials: A
authors.lastname: Jose
authors.affiliation: a Department of Pharmacy , Birla Institute of Technology and Science (BITS) Pilani , Hyderabad Campus , Hyderabad , Telangana , India.
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Mandapalli
authors.affiliation: a Department of Pharmacy , Birla Institute of Technology and Science (BITS) Pilani , Hyderabad Campus , Hyderabad , Telangana , India.
authors.forename: Venkata Vamsi Krishna
authors.initials: VV
authors.lastname: Venuganti
mesh_terms: D000287:Administration, Topical; D000818:Animals; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004423:Ear; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry*; D008081:Liposomes; D010316:Particle Size; D010539:Permeability; D011728:Pyridones / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013499:Surface Properties; D013552:Swine
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D011728:Pyridones; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C093844:pirfenidone
keywords: Encapsulation efficiency; HPMC hydrogel; liposome; pirfenidone; skin permeation