Formulation of orodispersible films for paediatric therapy: investigation of feasibility and stability for tetrabenazine as drug model.
OBJECTIVE
Orodispersible films (ODF) were formulated to facilitate tetrabenazine (TBZ) administration to paediatric population for the treatment of hyperkinetic movement disorders.


METHODS
ODF were obtained by solvent casting/evaporation method using four different polymers (HPMC, PVP, pullulan and HEC). Physicochemical, mechanical and biopharmaceutical characterizations as well as API state in ODF by thermal analysis were investigated to define and compare formulations. ODF stability was also monitored during 6 months to follow evolution of properties.


RESULTS
Analyses at T0 showed few differences between formulations: results of physicochemical and mechanical characterizations were almost similar for each formulation and TBZ appeared at the amorphous state in all cases. ODF delivery system allowed a major improvement of TBZ dissolution profile in buccal conditions compared with pure drug. However, after 3 and 6 months of stability, a TBZ recrystallization occurred for formulations based on PVP and HEC associated with a decrease of drug release in saliva conditions.


CONCLUSIONS
HPMC-ODF (F1) appeared as the best formulation. Indeed, physicochemical, mechanical and biopharmaceutical characteristic remained intact. In addition, TBZ remained in amorphous state during stability study.
Université de Lyon, Université Lyon 1, Laboratoire d'Automatique et de Génie des Procédés (LAGEP), UMR CNRS 5007, Villeurbanne, France.
Zoé
Z
Senta-Loys
Université de Lyon, Université Lyon 1, Laboratoire d'Automatique et de Génie des Procédés (LAGEP), UMR CNRS 5007, Villeurbanne, France.|Université de Lyon, Université Lyon 1, ISPB-Faculté de Pharmacie, Lyon, France.
Sandrine
S
Bourgeois
Université de Lyon, Université Lyon 1, ISPB-Faculté de Pharmacie, Lyon, France.|Université de Lyon, Ecole Centrale de Lyon, Laboratoire de Tribologie et Dynamique des Systèmes, UMR CNRS 5513, Ecully, France.
Cyril
C
Pailler-Mattei
Université de Lyon, Université Lyon 1, Laboratoire d'Automatique et de Génie des Procédés (LAGEP), UMR CNRS 5007, Villeurbanne, France.
Géraldine
G
Agusti
Université de Lyon, Université Lyon 1, Laboratoire d'Automatique et de Génie des Procédés (LAGEP), UMR CNRS 5007, Villeurbanne, France.|Université de Lyon, Université Lyon 1, ISPB-Faculté de Pharmacie, Lyon, France.
Stéphanie
S
Briançon
Université de Lyon, Université Lyon 1, Laboratoire d'Automatique et de Génie des Procédés (LAGEP), UMR CNRS 5007, Villeurbanne, France.|Université de Lyon, Université Lyon 1, ISPB-Faculté de Pharmacie, Lyon, France.
Hatem
H
Fessi
D000278:Administration, Buccal; D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical / Q000379:methods; D065546:Drug Liberation / Q000187:drug effects; D004355:Drug Stability; D006801:Humans; D006948:Hyperkinesis / Q000188:drug therapy; D065568:Oral Mucosal Absorption; D011108:Polymers / Q000737:chemistry; D012463:Saliva / Q000378:metabolism; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013747:Tetrabenazine / Q000008:administration & dosage / Q000737:chemistry*
D011108:Polymers; D012997:Solvents; D013747:Tetrabenazine

HPMC
; 
PVP
; orodispersible film; paediatric medicine; tetrabenazine