title: Vaginal distribution and retention of a multiparticulate drug delivery system, assessed by gamma scintigraphy and magnetic resonance imaging.
abstract: BACKGROUND
  For any new vaginal dosage form, the distribution and retention in the vagina has to be assessed by in vivo evaluation. We evaluated the vaginal distribution and retention of starch-based pellets in sheep as live animal model by gamma scintigraphy (using Indium-111 DTPA as radiolabel) and in women via magnetic resonance imaging (MRI, using a gadolinium chelate as contrast agent). A conventional cream formulation was used as reference in both studies.
  
  
  METHODS
  Cream and pellets were administered to sheep (n=6) in a two period-two treatment study and to healthy female volunteers (n=6) via a randomized crossover trial. Pellets (filled into hard gelatin capsule) and cetomacrogol cream, both labeled with Indium-111 DTPA (for gamma scintigraphy) or with gadolinium chelate (for MRI) were evaluated for their intravaginal distribution and retention over a 24h period. Spreading in the vagina was assessed based on the part of the vagina covered with formulation (expressed in relation to the total vaginal length). Vaginal retention of the formulation was quantified based on the radioactivity remaining in the vaginal area (sheep study), or qualitatively evaluated (women study).
  
  
  RESULTS
  Both trials indicated a rapid distribution of the cream within the vagina as complete coverage of the vaginal mucosa was seen 1h after dose administration. Clearance of the cream was rapid: about 10% activity remained in the vaginal area of the sheep 12h post-administration, while after 8h only a thin layer of cream was detected on the vaginal mucosa of women. After disintegration of the hard gelatin capsule, the pellet formulation gradually distributed over the entire vaginal mucosa. Residence time of the pellets in the vagina was longer compared to the semi-solid formulation: after 24h 23 ± 7% radioactivity was detected in the vaginal area of the sheep, while in women the pellet formulation was still detected throughout the vagina.
  
  
  CONCLUSIONS
  A multi-particulate system containing starch-based pellets was identified as a promising novel vaginal drug delivery system, resulting in complete coverage of the vaginal mucosa and long retention time.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
authors.forename: Samata
authors.initials: S
authors.lastname: Mehta
authors.affiliation: Department of Obstetrics and Gynecology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: Verstraelen
authors.affiliation: Department of Radiology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Kathelijne
authors.initials: K
authors.lastname: Peremans
authors.affiliation: Department of Medical Imaging, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Villeirs
authors.affiliation: Department of Radiology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Simon
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Laboratory of Radiopharmacy, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: De Vos
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Mehuys
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. Electronic address: chris.vervaet@ugent.be.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D000282:Administration, Intravaginal; D000328:Adult; D000818:Animals; D002214:Capsules; D002592:Cetomacrogol / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003287:Contrast Media / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008536:Meglumine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D023421:Models, Animal; D009092:Mucous Membrane / Q000000981:diagnostic imaging / Q000378:metabolism; D009824:Ointments; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012756:Sheep; D013213:Starch / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D014621:Vagina / Q000000981:diagnostic imaging* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D002214:Capsules; D003287:Contrast Media; D004337:Drug Carriers; D009824:Ointments; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013501:Surface-Active Agents; D008536:Meglumine; D004369:Pentetic Acid; D002592:Cetomacrogol; D013213:Starch; C072417:gadoterate meglumine