title: Nano-transfersomal formulations for transdermal delivery of asenapine maleate: in vitro and in vivo performance evaluations.
abstract: BACKGROUND
  Asenapine maleate (ASPM) is an antipsychotic drug for the treatment of schizophrenia and bipolar disorder. Extensive metabolism makes the oral route inconvenient for ASPM.
  
  
  OBJECTIVE
  The objective of this study is to increase ASPM bioavailability via transdermal route by improving the skin permeation using combined strategy of chemical and nano-carrier (transfersomal) based approaches.
  
  
  METHODS
  Transfersomes were prepared by the thin film hydration method using soy-phosphatidylcholine (SPC) and sodium deoxycholate (SDC). Transfersomes were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, surface morphology, and in vitro skin permeation studies. Various chemical enhancers were screened for skin permeation enhancement of ASPM. Optimized transfersomes were incorporated into a gel base containing suitable chemical enhancer for efficient transdermal delivery. In vivo pharmacokinetic study was performed in rats to assess bioavailability by transdermal route against oral administration.
  
  
  CONCLUSIONS
  Optimized transfersomes with drug:SPC:SDC weight ratio of 5:75:10 were spherical with an average size of 126.0 nm, PDI of 0.232, ZP of -43.7 mV, and entrapment efficiency of 54.96%. Ethanol (20% v/v) showed greater skin permeation enhancement. The cumulative amount of ASPM permeated after 24 h (Q24) by individual effect of ethanol and transfersome, and in combination was found to be 160.0, 132.9, and 309.3 μg, respectively, indicating beneficial synergistic effect of combined approach. In vivo pharmacokinetic study revealed significant (p < 0.05) increase in bioavailability upon transdermal application compared with oral route.
  
  
  CONCLUSIONS
  Dual strategy of permeation enhancement was successful in increasing the transdermal permeation and bioavailability of ASPM.
authors.affiliation: a Department of Pharmaceutics , Manipal College of Pharmaceutical Sciences , Manipal , Karnataka State , India.
authors.forename: A B
authors.initials: AB
authors.lastname: Shreya
authors.affiliation: a Department of Pharmaceutics , Manipal College of Pharmaceutical Sciences , Manipal , Karnataka State , India.
authors.forename: Renuka S
authors.initials: RS
authors.lastname: Managuli
authors.affiliation: a Department of Pharmaceutics , Manipal College of Pharmaceutical Sciences , Manipal , Karnataka State , India.
authors.forename: Jyothsna
authors.initials: J
authors.lastname: Menon
authors.affiliation: a Department of Pharmaceutics , Manipal College of Pharmaceutical Sciences , Manipal , Karnataka State , India.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Kondapalli
authors.affiliation: a Department of Pharmaceutics , Manipal College of Pharmaceutical Sciences , Manipal , Karnataka State , India.
authors.forename: Aswathi R
authors.initials: AR
authors.lastname: Hegde
authors.affiliation: a Department of Pharmaceutics , Manipal College of Pharmaceutical Sciences , Manipal , Karnataka State , India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Avadhani
authors.affiliation: a Department of Pharmaceutics , Manipal College of Pharmaceutical Sciences , Manipal , Karnataka State , India.
authors.forename: Pallavi K
authors.initials: PK
authors.lastname: Shetty
authors.affiliation: a Department of Pharmaceutics , Manipal College of Pharmaceutical Sciences , Manipal , Karnataka State , India.
authors.forename: Muthukumar
authors.initials: M
authors.lastname: Amirthalingam
authors.affiliation: b Department of Clinical Embryology , Kasturba Medical College , Manipal , Karnataka State , India.
authors.forename: Guruprasad
authors.initials: G
authors.lastname: Kalthur
authors.affiliation: a Department of Pharmaceutics , Manipal College of Pharmaceutical Sciences , Manipal , Karnataka State , India.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Mutalik
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003986:Dibenzocycloheptenes; D004339:Drug Compounding; D016503:Drug Delivery Systems; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; C522667:asenapine
keywords: Asenapine maleate; bioavailability; ethanol; transdermal; transfersomes