Nicotine - Magnesium Aluminum Silicate Microparticles: In vitro Evaluations

Abstract

Abstract

Introduction: Nicotine (NCT) has been used for smoking cessation. It can interact with magnesium aluminum silicate (MAS), a negatively charged clay, via electrostatic interaction and hydrogen bonding, leading to the formation of NCT-MAS complex flocculates. The aim of this study was to prepare NCT-MAS microparticles by using lyophilization in order to maintain the original morphology of the NCT-MAS flocculates. Effects of pH and NCT-MAS ratio on the characteristics of the microparticles were investigated. Materials and method: NCT-MAS microparticles were prepared by varying preparation pHs and NCT-MAS ratios. NCT (in aqueous solution) was dropped into MAS suspension at pH 4 or pH 7 to obtain NCT-MAS ratios of 0.05:1, 0.10:1, and 0.20:1. The microparticles were collected by filtration and dried by lyophilization. The general appearances and physicochemical properties of microparticles were investigated, such as crystallinity by PXRD, thermal behavior by DSC, mucoadhesion properties by texture analyzer, and drug release and permeation behavior by using Franz diffusion cell.  Results: The obtained microparticles had an irregular shape. The size and NCT content of the microparticles increased from 105 to 200 µm and 4.7 to 15.7 %, respectively, when increasing the NCT amount. The shifting of basal spacing peak in PXRD patterns to lower angle indicated increasing of interlayer space of MAS which supposed that NCT could intercalate into the MAS layers. Intercalation of NCT into the MAS layers enhanced thermal stability of NCT and resulted in a sustained release of NCT after an initial burst release. Microparticles prepared at pH 4 gave a lower permeation rate of NCT across porcine mucosal membrane than those prepared at pH 7. All of microparticles had mucoadhesion properties for adhesion to the porcine mucosa. Conclusion: These findings can deduce that the preparation pHs and NCT-MAS ratios of NCT-MAS microparticles could alter physicochemical properties, NCT release and NCT permeation across mucosal membrane. The NCT-MAS microparticles showed a good potential for drug delivery system with enhancing NCT stability, sustaining NCT release, and having mucoadhesive properties.