Synergy between surfactants and mucoadhesive polymers enhances the transbuccal permeation of local anesthetics from freeze-dried tablets

Author(s)

Silva Favacho, Hugo Alexandre ^[1] ; do Couto, Rene Oliveira ^[2] ; Ferreira Duarte, Maira Peres ^[3] ; Garofo Peixoto, Maria Paula ^[3] ; Vianna Lopez, Renata Fonseca ^[3] ; Pedrazzi, Vinicius ^[4] ; de Gaitani, Cristiane Masetto ^[3] ; de Freitas, Osvaldo ^[3]

Affiliation

^[1] Univ Fed Amapa, BR-68903419 Macapa, AP - Brazil

^[2] Univ Fed Sao Joao del Rei, Campus Ctr Oeste Dona Lindu, BR-35501296 Divinopolis, MG - Brazil

^[3] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Sch Odontol Ribeirao Preto, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Materials Science & Engineering C-Materials for Biological Applications; v. 108, MAR 2020.
• Web of Science Citations: 0

Abstract

We report on the advance of freeze-dried mucoadhesive orodispersible tablets (ODTs) loaded with prilocaine (PRC) and lidocaine (LDC) hydrochlorides, aiming to promote noninvasive buccal anesthesia. The influences of combining biocompatible polymers (pullulan and HPMC K100 LV) and a blend of surfactants (oleic acid, polysorbate 80 and propylene glycol) acting as chemical enhancers on the permeation of such drugs through the esophageal porcine epithelium and in vitro mucoadhesion were investigated. The ODTs were also characterized in terms of average weight, thickness, pH, drug content, in vitro release, thermal behavior and scanning electronic microscopy. A dissolution test showed fast drug release within one hour. The drug release data for all ODTs fitted first order. No significant influence of the type of mucoadhesive polymer on release was observed, while the drug release from ODTs decreased in the presence of chemical enhancers. For the ODT containing pullulan the drug release mechanism was anomalous transport, whist for all others it was case-II transport. A remarkable synergic effect between pullulan and chemical enhancers on the permeation flux, lag time, and permeability coefficient of both drugs, but mainly for PRC was observed. Pullulan together with permeation enhancers also substantially improved the work of mucoadhesion as compared to HPMC. In contrast, HPMC improved drug retention in the epithelium. The novel drug delivery platform achieved by combining a freezedrying technique, mucoadhesive biocompatible polymers, and chemical permeation enhancers displayed an effective strategy for the transbuccal delivery of PRC and LDC that can be used to improve needle-free buccal anesthesia. (AU)

• FAPESP's process: 12/05644-0 - Development of mucoadhesive semisolid systems for anesthetic release and iontophoresis application on the buccal cavity
• Grantee: Camila Cubayachi
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/06167-1 - Development of mucoadhesive films for anesthetic release on the buccal cavity
• Grantee: Renê Oliveira Do Couto
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/07251-6 - Development of platform with mucoadhesive systems for drug release on the buccal cavity
• Grantee: Osvaldo de Freitas
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/12174-3 - Study of resorbable polymers: the effect of degradation and erosion on dye release
• Grantee: Renê Oliveira Do Couto
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 14/22451-7 - Sustained drug delivery systems targeting the epithelial tissue
• Grantee: Renata Fonseca Vianna Lopez
• Support Opportunities: Research Projects - Thematic Grants