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

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/cm 2 ) in the mechanical properties of buccal films. Methods: A quality by design (QbD) approach based on a full factorial design (3 x 2 3 ) 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.

An insight into polyscopoletin electrosynthesis by a quality-by-design approach

“…In this work, a Box–Behnken experimental design (BBD) based on a 3 3 matrix was used [ 36 ]; thus, three factors were selected and three levels were tested for each factor. The Box–Behnken experimental designed was selected, among others, due to the high reproducibility of its model, despite having limited capacity of predicting borderline nonlinear design spaces [ 34 , 36 ]. Notwithstanding, the Box–Behnken experimental design often showcases better fitting than other multifactorial approaches, such as the 3 3 full factorial, central composite and Doehlert design [ 36 ].…”

“…Often, as observed in Table 1 , the experimental parameters vary from one work to another, without a rational explanation from the authors as to why they were specifically selected. Here, we propose the use of the quality-by-design approach [ 34 ], for the rational optimization of the experimental conditions of electrochemical synthesis of SP, based on the critical evaluation of the response variables (electroactive area and surface coverage) obtained after the execution of the planned experimental design. Electroactive area was herein selected as a dependent variable because of its effects on electric current and the implication of this parameter in sensing applications.…”

The Potential of Films as Transmucosal Drug Delivery Systems

“…Formulators also should consider that the drug exerts a plasticizing effect in the polymeric films by itself, which can be explained along the same lines as the aforementioned for any other small substance displaying binding functional groups. There is convincing evidence that increasing the drug loading correlates with a decrease in the glass transition temperature of polymers [33], which in turn correlates with a decrease in the tensile strength and tensile modulus of films [33,34]. Therefore, owing to this likely synergic effect, the amount of both the plasticizer and drug in the film should be set while seeking to balance the ideal mechanical properties and improved treatment outcomes.…”

“…Finally, it is worth mentioning that the study of the best polymers, plasticizers, and drug loading for the formulation is of paramount importance, since the same plasticizer may have different effects on different polymers [35]. For instance, mannitol can make HPMC films more resistant, while glycerol can make them more plastic [34]. Feasible strategies to be used in this pursuit are the Quality by Design (QbD) approaches such as the Design of Experiments (DoE) and Response Surface Methodology (RSM) [34,36].…”

“…For instance, mannitol can make HPMC films more resistant, while glycerol can make them more plastic [34]. Feasible strategies to be used in this pursuit are the Quality by Design (QbD) approaches such as the Design of Experiments (DoE) and Response Surface Methodology (RSM) [34,36].…”