title: Formulation of bioadhesive hexylaminolevulinate pellets intended for photodynamic therapy in the treatment of cervical cancer.
abstract: Photodynamic therapy has a great potential in the treatment of cervical cancer. The aim of this study was to develop bioadhesive pellets containing hexylaminolevulinate (HAL), a precursor of the photoactive substance PpIX, with a fast release for vaginal drug delivery. Pellets were produced by extrusion/spheronization, and Carbopol(®) 934 was used to obtain bioadhesive properties. A 2(2)-factorial design with center point investigating the HAL content (1 and 10%, w/w) and Carbopol(®) 934 content (1 and 8%, w/w) was set up. The most suitable formulations were mechanically stable and showed bioadhesive properties toward vaginal tissue. The drug load was released within 20 min in phosphate buffer pH 4 and 6.8 in the in vitro dissolution test. The stability of HAL in the pellet formulations varied, but the most stable formulation showed 96-97% HAL remaining in the formulation after 6-7 weeks of storage at accelerated temperature conditions (40 °C). The investigated formulations seem promising for vaginal delivery of HAL.
authors.affiliation: The SiteDel Group, Department of Pharmacy, School of Pharmacy, University of Oslo, Norway. marianne.hiorth@farmasi.uio.no
authors.forename: Marianne
authors.initials: M
authors.lastname: Hiorth
authors.forename: Linda
authors.initials: L
authors.lastname: Liereng
authors.forename: Reidun
authors.initials: R
authors.lastname: Reinertsen
authors.forename: Ingunn
authors.initials: I
authors.lastname: Tho
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000268:Adhesiveness; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D002417:Cattle; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry; D005260:Female; D009092:Mucous Membrane / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D013696:Temperature; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy; D014621:Vagina / Q000378:metabolism*
chemical_list: D000179:Acrylates; D005079:Excipients; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester; C453622:carbopol 934P