Quality by Design-driven investigation of the mechanical properties of mucoadhesive films for needleless anesthetics administration

Luiz Fernando Machado  Ferreira; Douglas Vieira  Thomaz; Maíra Peres Ferreira  Duarte; Renata Fonseca Vianna  Lopez; Vinícius  Pedrazzi; Osvaldo  de Freitas; Renê Couto

Luiz Fernando Machado Ferreira Campus Centro-Oeste Dona Lindu (CCO), Universidade Federal de São João del Rei (UFSJ), Divinópolis, MG, Brasil
Douglas Vieira Thomaz Faculdade de Farmácia (FF), Universidade Federal de Goiás (UFG), Goiânia, GO, Brasil https://orcid.org/0000-0003-0000-3466
Maíra Peres Ferreira Duarte Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP), Universidade de São Paulo (USP), Ribeirão Preto, SP, Brasil
Renata Fonseca Vianna Lopez Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP), Universidade de São Paulo (USP), Ribeirão Preto, SP, Brasil https://orcid.org/0000-0002-6448-6711
Vinícius Pedrazzi Faculdade de Odontologia de Ribeirão Preto (FORP), Universidade de São Paulo (USP), Ribeirão Preto, SP, Brasil https://orcid.org/0000-0003-0701-6999
Osvaldo de Freitas Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP), Universidade de São Paulo (USP), Ribeirão Preto, SP, Brasil https://orcid.org/0000-0001-7055-2028
Renê Couto Campus Centro-Oeste Dona Lindu (CCO), Universidade Federal de São João del Rei (UFSJ), Divinópolis, MG, Brasil https://orcid.org/0000-0002-3748-3427

Keywords: Biocompatible Materials, Buccal Drug Administration, Hypromellose Derivatives, Lidocaine Prilocaine Drug Combination, Multivariate analysis, Polymers

Abstract

Objectives: To systematically evaluate the effects of hydroxypropyl methyl cellulose (HPMC) type (E5LV, E15LV, and K100LV); plasticizer type (glycerol and mannitol), plasticizer loading (0.12 and 0.24% w/w); and loading of prilocaine and lidocaine hydrochlorides combined at 1:1 ratio (0 and 47 mg/cm2) in the mechanical properties of buccal films. Methods: A quality by design (QbD) approach based on a full factorial design (3 x 23) and complementarily multivariate statistical tools i.e., principal component analysis (PCA), response surface methodology (RSM), and correlation matrix were used in this pursuit. The thickness, elongation at break, tensile strength, force at break, and Young`s modulus of the anesthetic buccal films obtained by solvent casting were assessed. Results: The QbD, PCA and RSM altogether demonstrated that all studied formulation variables, mainly the drug loading, affect the mechanical properties of the films at different significance levels. The multivariate analysis yielded the modelling of elongation at break, tensile strength, and force at break, which significantly correlated with each other. The drugs exerted a synergic plasticizing effect on the films, and the use of HPMC K100 LV (with greater hydroxypropyl substitution degree and viscosity) and mannitol favored their elasticity and resistance. Furthermore, the majority of the films fulfilled the requirements for buccal administration due to their softness and mechanical resistance. Conclusion: Mannitol is suitable plasticizer for manufacturing HPMC anesthetic buccal films with improved mechanical properties. These results are a step forward in the rational development of formulations for the replacement of needles in dentistry