title: Effect of permeability enhancers on paracellular permeability of acyclovir.
abstract: OBJECTIVE
  According to Biopharmaceutics Classification System (BCS), acyclovir is a class III (high solubility, low permeability) compound, and it is transported through paracellular route by passive diffusion. The aim of this study was to investigate the effect of various pharmaceutical excipients on the intestinal permeability of acyclovir.
  
  
  METHODS
  The single-pass in-situ intestinal perfusion (SPIP) method was used to estimate the permeability values of acyclovir and metoprolol across different intestinal segments (jejunum, ileum and colon). Permeability coefficient (Peff ) of acyclovir was determined in the absence and presence of a permeation enhancer such as dimethyl β-cyclodextrin (DM-β-CD), sodium lauryl sulfate (SLS), sodium caprate (Cap-Na) and chitosan chloride.
  
  
  RESULTS
  All enhancers increased the permeability of paracellularly transported acyclovir. Although Cap-Na has the highest permeability-enhancing effect in all segments, permeation-enhancing effect of chitosan and SLS was only significant in ileum. On the other hand, DM-β-CD slightly decreased the permeability in all intestinal segments.
  
  
  CONCLUSIONS
  These findings have potential implication concerning the enhancement of absorption of paracellularly transported compounds with limited oral bioavailability. In the case of acyclovir, Cap-Na either alone or in combination with SLS or chitosan has the potential to improve its absorption and bioavailability and has yet to be explored.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Technology, Hacettepe University, Ankara, Turkey.|Faculty of Pharmacy, Department of Pharmaceutical Technology, İnönü University, Malatya, Turkey.
authors.forename: Muge
authors.initials: M
authors.lastname: Ates
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Technology, İnönü University, Malatya, Turkey.
authors.forename: Mustafa Sinan
authors.initials: MS
authors.lastname: Kaynak
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Technology, Hacettepe University, Ankara, Turkey.
authors.forename: Selma
authors.initials: S
authors.lastname: Sahin
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D048271:Chitosan / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D010477:Perfusion; D010539:Permeability; D017207:Rats, Sprague-Dawley; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D003652:Decanoic Acids; D005079:Excipients; D047392:beta-Cyclodextrins; D012967:Sodium Dodecyl Sulfate; C031071:decanoic acid; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D048271:Chitosan; D000212:Acyclovir
keywords: chitosan; dimethyl β-cyclodextrin; permeation enhancer; sodium caprate; sodium lauryl sulfate