title: Orodispersible films based on amorphous solid dispersions of tetrabenazine.
abstract: In this work, the formation and stability of amorphous solid dispersions (SDs) as orodispersible films (ODF) were investigated using tetrabenazine (TBZ) as a poorly water soluble drug. The influence of polymer nature and pH-modifier incorporation to form and maintain SDs was investigated. TBZ-loaded ODF were formulated using 4 different polymers (HPMC, PVP, Pullulan, and HEC). Binary systems (BS) were obtained mixing the drug with different polymers, while ternary (TS) systems were also obtained by adding citric acid to solubilize TBZ in the mixture. Drug dissolution studies, thermal analysis and X-ray diffraction were carried out to characterize the physical state of API in ODF. ODF made of TS allowed a major improvement of TBZ dissolution profile in buccal conditions compared to a pure drug or BS. DSC and X-ray diffraction revealed that API was in amorphous state in TS while remained crystalline in BS. Following 6 months of storage, TBZ recrystallization occurred for PVP-TS and HEC-TS which induced a decrease of drug release in saliva conditions. HPMC and PUL-TS maintained API in amorphous state during 6 months. Briefly, amorphous SDs were obtained by the pre-dissolution of the drug in acidified water and incorporation in polymeric films. The miscibility and potential interaction between TBZ and polymers have been identified as important factor to explain stability differences.
authors.affiliation: Université de Lyon, Université Claude Bernard-Lyon 1, CNRS, LAGEP UMR 5007, 43 boulevard du 11 novembre 1918, F-69622, Villeurbanne, France.
authors.forename: Zoé
authors.initials: Z
authors.lastname: Senta-Loys
authors.affiliation: Université de Lyon, Université Claude Bernard-Lyon 1, CNRS, LAGEP UMR 5007, 43 boulevard du 11 novembre 1918, F-69622, Villeurbanne, France; Université de Lyon, Université Claude Bernard-Lyon 1, ISPB-Faculté de Pharmacie, 8 Avenue Rockefeller, F-69008, Lyon, France. Electronic address: sandrine.bourgeois@univ-lyon1.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bourgeois
authors.affiliation: Université de Lyon, Université Claude Bernard-Lyon 1, CNRS, LAGEP UMR 5007, 43 boulevard du 11 novembre 1918, F-69622, Villeurbanne, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Valour
authors.affiliation: Université de Lyon, Université Claude Bernard-Lyon 1, CNRS, LAGEP UMR 5007, 43 boulevard du 11 novembre 1918, F-69622, Villeurbanne, France; Université de Lyon, Université Claude Bernard-Lyon 1, ISPB-Faculté de Pharmacie, 8 Avenue Rockefeller, F-69008, Lyon, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Briançon
authors.affiliation: Université de Lyon, Université Claude Bernard-Lyon 1, CNRS, LAGEP UMR 5007, 43 boulevard du 11 novembre 1918, F-69622, Villeurbanne, France; Université de Lyon, Université Claude Bernard-Lyon 1, ISPB-Faculté de Pharmacie, 8 Avenue Rockefeller, F-69008, Lyon, France.
authors.forename: Hatem
authors.initials: H
authors.lastname: Fessi
mesh_terms: D002152:Calorimetry, Differential Scanning; D019343:Citric Acid / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D005990:Glycerol / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008855:Microscopy, Electron, Scanning; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D013012:Sorbitol / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013747:Tetrabenazine / Q000737:chemistry*; D044366:Transition Temperature; D014961:X-Ray Diffraction
chemical_list: D011108:Polymers; D019343:Citric Acid; D013012:Sorbitol; D005990:Glycerol; D013747:Tetrabenazine
keywords: Amorphous solid dispersion; Citric acid; HPMC; Orodispersible film; PVP; Tetrabenazine