title: Modified-release ointment with nitroglycerin β-cyclodextrin inclusion complex for treatment of anal fissures.
abstract: OBJECTIVE
  The aim was to evaluate ointments for local treatment of anal fissures. Nitroglycerin (NTG) was complexed with β-cyclodextrin (β-CD) to provide prolonged NTG release, with the intention of decreasing systemic drug absorption and thus reducing side effects.
  
  
  METHODS
  Gels, creams and anhydrous water-emulsifying (AWE) ointment with NTG-CD were compared with preparations containing uncomplexed NTG (diluted with crospovidone, NTG-cP). The in-vitro NTG release and ex-vivo skin absorption were studied.
  
  
  RESULTS
  The prolonged-release ointment with the NTG-CD complex was formulated using AWE base or w/o cream (20% water); release of NTG from a hydrogel was very fast with both the complexed and uncomplexed forms. From the AWE ointment base, 16.4% or 4.5% of the total NTG dose was released after 6 h when NTG-cP or NTG-CD was incorporated, respectively. With the complexed form, NTG absorption to the skin after a 5-h application was 18.1 or 11.1 μg/g from AWE ointment or cream, respectively; absorption of the uncomplexed NTG was higher: 52.3 or 21.9 μg/g from AWE ointment and cream, respectively.
  
  
  CONCLUSIONS
  Complexation with β-CD results in prolonged release of NTG from AWE ointment and w/o cream, which was confirmed by the ex-vivo skin absorption results.
authors.affiliation: Department of Pharmaceutical Technology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Centkowska
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Sznitowska
mesh_terms: D000328:Adult; D002102:Cadaver; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D005401:Fissure in Ano / Q000188:drug therapy*; D006801:Humans; D020100:Hydrogels; D066298:In Vitro Techniques; D005996:Nitroglycerin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009824:Ointments; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D009824:Ointments; D047392:beta-Cyclodextrins; D005996:Nitroglycerin
keywords: anal fissures; nitroglycerin; ointment; prolonged release; β-cyclodextrin