Freeze-Dried Matrices for Buccal Administration of Propranolol in Children: Physico-Chemical and Functional Characterization

Abstract

Buccal matrices represent a widely accepted dosage form permitting a convenient, easy, reliable drug administration and reducing administration errors. The aim of this study was the development of mucoadhesive buccal matrices for propranolol administration in children. Matrices were obtained by freeze-drying of drug loaded polymeric solutions based on gum tragacanth (GT), pectin (PEC), hydroxypropylmethylcellulose (HPMC), sodium hyaluronate (HA), gelatin (GEL), chitosan (CH) or a mixture of CH and HPMC (CH/HPMC). Matrices were characterized for drug solid state, morphology, water-uptake, mucoadhesion ability, in vitro drug release and permeation through porcine epithelium. The most promising formulations were tested for in vitro biocompatibility in human dental pulp fibroblasts. The preparative method and the polymeric composition influenced the drug solid state, as a complete amorphization as well as different polymorphic forms were observed. GEL and PEC guaranteed a fast and complete drug release due to their rapid dissolution, while for the other matrices the release was influenced by drug diffusion through the viscous gelled matrix. Moreover, matrices based on CH and CH/HPMC showed the best mucoadhesive properties, favoured the drug permeation, in virtue of CH ability to interfere with the lipid organization of biological membrane, and were characterized by a good biocompatibility profile.

Keywords: Buccal delivery; Lyophilization; Mucoadhesive; Pediatric; Polymeric drug delivery systems; Solid-state.