Design and characterization of bilayered buccal films as paediatric dosage form for systemic administration of propranolol

Buccal mucosa has emerged as an attractive site for systemic administration of drug in paediatric patients. This route is simple and non-invasive, even if the saliva wash-out effect and the relative permeability of the mucosa can reduce drug absorption (Lam et al., 2014). Mucoadhesive polymers represent a common employed strategy to increase the contact time of the formulation at the application site and to improve drug absorption. Among the different mucoadhesive dosage forms, buccal films are particularly addressed for paediatric population since they are thin, adaptable to the mucosal surface and able to offer an exact and flexible dose (Borges et al., 2015; Trastullo et al., 2016). The objective of the present study was to develop bilayered buccal films for the release of propranolol hydrochloride, a non-selective β1 and β2 adrenergic antagonist, indicated in paediatrics for the treatment of hypertension. Mucoadhesive layer was prepared by casting and drying of solutions of film-forming polymers, such as polyvinylpyrrolidone (PVP) or polyvinylalcohol (PVA), added with different weight ratios of gelatin (GEL) or chitosan (CH). In order to achieve unidirectional drug delivery towards buccal mucosa, an ethylcellulose coating layer was applied onto the first one. Bilayered films were characterized for their physico-chemical and functional properties. The inclusion of CH into PVP and PVA films provided the best mucoadhesion ability, probably due to their highest hydration among all the formulations, that ensured a good interpenetration and entanglement between polymer and mucin chains. Moreover, the positively charged ammino groups of CH could interact with negatively charged sialic acid and sulphate residues of mucin glycoprotein. Films containing CH provided a lower drug release with respect to films containing GEL, due to their lower viscosity in the gelled state which limited drug diffusion. The presence of CH also increased the amount of permeated drug through buccal mucosa, thanks to its ability of interfering with the lipid organization. Coating layer did not interfere with drug permeation, but it could limit drug release in the buccal cavity. With polymeric films, a novel solid buccal formulation was developed. The selection of suitable polymeric mixture allowed the modulation of the mucoadhesive ability, the release of the drug and its permeation through the buccal mucosa. Moreover, polymeric films fulfill all current demands for child-appropriate dosage forms. In fact, they combine the convenience of tablets, a solid dosage form, with less issues instability than liquid formulations, and the opportunity to avoid swallowing of a large unit. Moreover, the use of films with different sizes enables the administration of variable doses of drug and can be suitable for a large range of age groups. Borges A.F., Silva C., Coelho J.F., Simões S. Oral films: current status and future perspectives. I – Galenical development and quality attributes. J. Control. Release 206 (2015) 1-19. Lam J.K., Xu Y., Worsley A., Wong I.C. Oral transmucosal drug delivery for pediatric use. Adv. Drug Deliv. Rev. 73 (2014) 50-62. Trastullo R., Abruzzo A., Saladini B., Gallucci M.C., Cerchiara T., Luppi B., Bigucci F. Design and evaluation of buccal films as paediatric dosage form for transmucosal delivery of ondansetron. Eur. J. Pharm. Biopharm. 105 (2016) 115-121.