title: Chitosan based mucoadhesive nanoparticles of ketoconazole for bioavailability enhancement: formulation, optimization, in vitro and ex vivo evaluation.
abstract: OBJECTIVE
  The conventional dosage form of Ketoconazole (KZ) shows poor absorption due to rapid gastric emptying. Chitosan based mucoadhesive nanoparticles (NPs) of KZ were developed to efficiently release drug at its absorption window i.e. stomach and the site of action i.e. esophagus.
  
  
  METHODS
  The NPs were prepared by ionic gelation method. Concentration of polymer, cross-linking agent and ratio of drug/polymer as well as polymer/cross linking agent were optimized.
  
  
  RESULTS
  NPs had 69.16 ± 5.91% mucin binding efficiency, particle size of 382.6 ± 2.384 nm, ζ potential of +48.1 mv and entrapment efficiency of 59.84 ± 1.088%. DSC thermogram indicated absence of any drug polymer interaction. The drug release was by controlled, non-fickian diffusion mechanism. Ex vivo diffusion studies were performed by emptying the stomach contents after 2 h to simulate in vivo gastric emptying. The results showed that drug diffusion from the solution across stomach mucosa stopped after emptying whereas that from the NPs continued upto 5 h. Hence we could conclude that the NPs must have adhered to the stomach mucosa and thereby would have been retained at this absorption site even after gastric emptying.
  
  
  CONCLUSIONS
  The orally delivered KZ loaded mucoadhesive NPs can be used as an efficient carrier for delivering drug at its absorption window i.e. the stomach and the site of action i.e. esophagus even after gastric emptying.
authors.affiliation: TIFAC Centre of Relevance and Excellence in NDDS, Centre of PG Studies and Research, Pharmacy Department, The M. S. University of Baroda, Fatehgunj, Vadodara, Gujarat, India.
authors.forename: Jigar
authors.initials: J
authors.lastname: Modi
authors.forename: Garima
authors.initials: G
authors.lastname: Joshi
authors.forename: Krutika
authors.initials: K
authors.lastname: Sawant
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D048271:Chitosan / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004947:Esophagus / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D007654:Ketoconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011817:Rabbits
chemical_list: D000935:Antifungal Agents; D048271:Chitosan; D007654:Ketoconazole