title: Sildenafil vaginal suppositories: preparation, characterization, in vitro and in vivo evaluation.
abstract: OBJECTIVE
  The main objective was to investigate the in vitro release profile/kinetics, and in vivo plasma pharmacokinetics (PK) and organ biodistribution (BD) of the prepared sildenafil vaginal suppositories (SVS).
  
  
  METHODS
  Suppositories containing 25 mg of sildenafil were prepared by the cream melting technique using Witepsol H-15 as a suppository base. The suppositories were characterized for weight variation, content uniformity, hardness, disintegration time and crystallinity change. The in vitro dissolution in pH 4.5, and in vivo plasma PK and organ BD of sildenafil from SVS in female Sprague Dawley rats, were also investigated.
  
  
  RESULTS
  The mean weight variation, content uniformity, hardness and disintegration time of the prepared SVS were 1.127 ± 0.020 g, 98.25 ± 2.50%, 2.5 ± 0.08 kg and 9 ± 1.0 min, respectively. The release of sildenafil from the SVS was more than 90% at 30 min, with a release kinetic of Hixson--Crowell model and non-Fickian diffusion (n = 0.464). The plasma PK study demonstrated a significantly lower Cmax (∼10 times) and AUC0-24 h (∼13 times) of sildenafil in plasma following intravaginal (IVG) administration of suppositories compared to oral (PO) administration of sildenafil solution. Nevertheless, the organ BD study showed a phenomenally higher Cmax (∼40 times) and AUC0-24 h (∼20 times) of sildenafil in uterus following IVG administration of suppositories than PO administration of sildenafil solution.
  
  
  CONCLUSIONS
  This study demonstrated enhanced sildenafil exposure in the uterus following IVG administration of SVS, which could be used to target the uterus for therapeutic benefits.
authors.affiliation: Pharm. R&D Institute, Hanmi Pharm. Co., Ltd. , Hwasung, Gyeonggi , South Korea .
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Shanmugam
authors.forename: Young-Hun
authors.initials: YH
authors.lastname: Kim
authors.forename: Jeong-Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Ho Taek
authors.initials: HT
authors.lastname: Im
authors.forename: Young Taek
authors.initials: YT
authors.lastname: Sohn
authors.forename: Kyeong Soo
authors.initials: KS
authors.lastname: Kim
authors.forename: Yong-Il
authors.initials: YI
authors.lastname: Kim
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Woo
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D005260:Female; D009928:Organ Specificity; D010879:Piperazines / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D011687:Purines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D013488:Suppositories; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D013488:Suppositories; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate
keywords: Intravaginal delivery; PK/biodistribution; release kinetics; sildenafil; vaginal suppositories