Track: Formulation and Delivery - Chemical - Drug Delivery - Other Routes of Administration - Other
Category: Poster Abstract
Evaluating 1,4-Dioxane as Permeability Enhancer Using Lidocaine as Model Drug in a Film Drug Dosage Form for Buccal and Sublingual Administration
Purpose: 1,4-Dioxane has been investigated computationally using MD simulations and have found that the molecule can be used as permeability enhancer. The presence of 1,4-Dioxane molecule leads to the change in lipid structure including reduction of the orderliness of lipid tails, membrane thickness and compressibility modulus. All these changes increase the permeability through the lipid cell layer. Therefore, the molecule has potential to be used as permeability enhancer in drug formulation. Permeability enhancing agent is an important part of a film dosage form. The quickly soluble film dosage form is administered in the buccal or sublingual area of mouth cavity. The major advantage of buccal or sublingual administration is these routes can avoid hepatic first pass effect. Besides, many other advantages such as oral mucosa's accessibility, excellent blood supply, and rapid repair and permeability profile, make buccal and sublingual routes extremely attractive for local and systemic drug delivery. The goal of this research is to determine the permeability enhancing ability of 1,4-dioxane while using in lidocaine as model drug in a film dosage form. Methods: A film dosage form was prepared by solvent casting method in petri dishes. Polymers Kollidon F90 and Kollidon VA64 were used as hydrophilic polymeric carriers and PEG 3350 was used as plasticizer for the oral films. The film was characterized in terms of disintegration time, film thickness, tensile strength, and drug permeability capability. Cytotoxic study of the film was also conducted in an epithelial cell layer as it contains 1,4-Dioxane as permeability enhancer. Disintegration time of the film were evaluated in artificial saliva. Film thickness was measured using Mitutoyo digital caliper. Tensile strength of the films was determined using Mark-10 digital force gauge. The permeation study of the film using lidocaine as sample drug was conducted using a Franz Cell. This study was conducted with a silicone membrane. Permeability of the drug was compared with or without presence of 1,4-Dioxane in the film. Permeability of the drug was measured using a UV-spectrophotometer. Results: The results show the average disintegration time for single layer study was 25.3 seconds, average thickness 0.103 mm, and the tensile strength 9.87 N. Cytotoxic study shows 1,4-Dioxane is not cytotoxic to epithelial cells. The permeation study of the drug in silicone membrane shows almost all drugs are permeable within few minutes through silicone membrane. However, there was no difference in permeability with ,4-Dioxane containing film. Conclusion: 1,4-Dioxane contained film was developed and characterized. The Dioxane found nontoxic to be used in the film dosage form if small quantity is added. The permeability study using a synthetic silicone membrane does not show any enhanced permeability while using Dioxane permeability enhancer in the film. Therefore, an in vitro cell study and an ex-vivo porcine membrane study will be conducted soon to observe the enhance permeability using Dioxane. References: 1. N.M.G. Almeida, R. Lima, T.F.R. Alves, M.A. De Rebelo, P. Severino, M.V. Chaud, A novel dosage form for buccal administration of bupropion, Brazilian J. Pharm. Sci. 51 (2015) 91–100. https://doi.org/10.1590/S1984-82502015000100010. 2. P.C. Chougule, M.R. Bhat, R.M. Chimkode, Design and Evaluation of Formulated Mouth Dissolving Film of Domperidone and Study the Effect of Concentration of Polymers on Drug Release, Asian J. Pharm. 11 (2017) 846–853.