Fabrication of Mucoadhesive Buccal Films for Local Administration of Ketoprofen and Lidocaine Hydrochloride by Combining Fused Deposition Modeling and Inkjet Printing

被引:64
|
作者
Eleftheriadis, Georgios K. [1 ]
Monou, Paraskevi Kyriaki [1 ]
Bouropoulos, Nikolaos [2 ,3 ]
Boetker, Johan [4 ]
Rantanen, Jukka [4 ]
Jacobsen, Jette [4 ]
Vizirianakis, Ioannis S. [5 ]
Fatouros, Dimitrios G. [1 ]
机构
[1] Aristotle Univ Thessaloniki, Dept Pharm, Lab Pharmaceut Technol, Thessaloniki 54124, Greece
[2] Univ Patras, Dept Mat Sci, Patras 26504, Greece
[3] Fdn Res & Technol Hellas, Inst Chem Engn & High Temp Chem Proc, Patras 26504, Greece
[4] Univ Copenhagen, Dept Pharm, DK-2100 Copenhagen, Denmark
[5] Aristotle Univ Thessaloniki, Dept Pharm, Pharmacol Lab, Thessaloniki 54124, Greece
关键词
3D printing; Mucosal delivery; Mucoadhesive; Transmucosal drug delivery; Epithelial permeability; Permeability enhancer; Buccal; Controlled release; TR146; CELL-CULTURE; HOT-MELT EXTRUSION; IN-VITRO; DOSAGE FORMS; DRUG-RELEASE; EX-VIVO; DELIVERY; DESIGN; FORMULATION; PERMEABILITY;
D O I
10.1016/j.xphs.2020.05.022
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
In the area of developing oromucosal drug delivery systems, mucoadhesive buccal films are the most promising formulations for either systemic or local drug delivery. The current study presents the fabrication of buccal films, by combining fused deposition modeling (FDM) and inkjet printing. Hydroxypropyl methylcellulose-based films were fabricated via FDM, containing the non-steroidal anti-inflammatory drug ketoprofen. Unidirectional release properties were achieved, by incorporating an ethyl cellulose-based backing layer. The local anesthetic lidocaine hydrochloride, combined with the permeation enhancer l-menthol, was deposited onto the film by inkjet printing. Physicochemical analysis showed alterations in the characteristics of the films, and the mucoadhesive and mechanical properties were effectively modified, due to the ink deposition on the substrates. The in vitro release data of the active pharmaceutical compounds, as well as the permeation profiles across ex vivo porcine buccal mucosa and filter-grown TR146 cells of human buccal origin, were associated with the presence of the permeation enhancer and the backing layer. The lack of any toxicity of the fabricated films was demonstrated by the MTT viability assay. This proof-of-concept study provides an alternative formulation approach of mucoadhesive buccal films, intended for the treatment of local oromucosal diseases or systemic drug delivery. (C) 2020 American Pharmacists Association (R) . Published by Elsevier Inc. All rights reserved.
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页码:2757 / 2766
页数:10
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