Introduction: The development of child-appropriated dosage forms represents one of the most important topics of new European regulations and recent WHO recommendations on paediatric medicines. Purpose: The aim of this study was the preparation and characterization of mucoadhesive polymeric films as suitable dosage form for transmucosal drug delivery. Method: An aqueous solution of hyaluronic acid (Mr 1800-2300 kDa; D-glucuronic acid > 42 %) and an acidic solution of chitosan (Mr 150 kDa; deacetylation degree 97 %) were separately added to an aqueous solution of hydroxypropylmethylcellulose (HPMC; methoxyl content 19-24 %; hydroxypropyl content 7-12 %) at different weight ratios (1:1, 3:7, 1:9, 0:10; hyaluronate/HPMC or chitosan/HPMC). Each mixture was stirred at room temperature for 24 hours, spreaded on a Petridish and dried at 50 °C for 6 h. Drug-free films and films with a child-appropriated dose of ondansetron hydrochloride were investigated. Physiochemical properties of the films (thickness, drug content, water uptake ability and mucoadhesion potential) and in vitro drug release were performed. Moreover, in vitro permeation studies will carry out in order to evaluate drug permeation through biological membranes. Results: Films were smooth and transparent, with good flexibility. The thickness was found to be uniform and drug content was close to the theoretical one (1 mg/cm2 for each film). Moreover, films showed good mucoadhesive properties and in particular the presence of hyaluronate allowed the highest mucoadhesion potential. Finally, the inclusion of chitosan in polymeric mixtures enhanced in vitro drug release with respect to the inclusion of hyaluronate, although chitosan/HPMC mixture showed the lowest water uptake. This behaviour could be attibuted to the high viscosity of the hyaluronate/HPMC films in the gel state. Conclusions: Our results indicate that buccal films based on different chitosan/HPMC and hyaluronate/HPMC mixtures could be used as a novel technological platform for paediatric medicines.
Ramona Trastullo, Valentina Ragazzini, Angela Abruzzo, Barbara Luppi, Teresa Cerchiara, Federica Bigucci (2013). Development of buccal films as novel dosage form for paediatric use.
Development of buccal films as novel dosage form for paediatric use
TRASTULLO, RAMONA;ABRUZZO, ANGELA;LUPPI, BARBARA;CERCHIARA, TERESA;BIGUCCI, FEDERICA
2013
Abstract
Introduction: The development of child-appropriated dosage forms represents one of the most important topics of new European regulations and recent WHO recommendations on paediatric medicines. Purpose: The aim of this study was the preparation and characterization of mucoadhesive polymeric films as suitable dosage form for transmucosal drug delivery. Method: An aqueous solution of hyaluronic acid (Mr 1800-2300 kDa; D-glucuronic acid > 42 %) and an acidic solution of chitosan (Mr 150 kDa; deacetylation degree 97 %) were separately added to an aqueous solution of hydroxypropylmethylcellulose (HPMC; methoxyl content 19-24 %; hydroxypropyl content 7-12 %) at different weight ratios (1:1, 3:7, 1:9, 0:10; hyaluronate/HPMC or chitosan/HPMC). Each mixture was stirred at room temperature for 24 hours, spreaded on a Petridish and dried at 50 °C for 6 h. Drug-free films and films with a child-appropriated dose of ondansetron hydrochloride were investigated. Physiochemical properties of the films (thickness, drug content, water uptake ability and mucoadhesion potential) and in vitro drug release were performed. Moreover, in vitro permeation studies will carry out in order to evaluate drug permeation through biological membranes. Results: Films were smooth and transparent, with good flexibility. The thickness was found to be uniform and drug content was close to the theoretical one (1 mg/cm2 for each film). Moreover, films showed good mucoadhesive properties and in particular the presence of hyaluronate allowed the highest mucoadhesion potential. Finally, the inclusion of chitosan in polymeric mixtures enhanced in vitro drug release with respect to the inclusion of hyaluronate, although chitosan/HPMC mixture showed the lowest water uptake. This behaviour could be attibuted to the high viscosity of the hyaluronate/HPMC films in the gel state. Conclusions: Our results indicate that buccal films based on different chitosan/HPMC and hyaluronate/HPMC mixtures could be used as a novel technological platform for paediatric medicines.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
