Clay-Polymer Nanocomposites Prepared by Reactive Melt Extrusion for Sustained Drug Release.

Xu Liu,Yongchao Su,Xingyu Lu,Eucharist Kun,Feng Zhang

doi:10.3390/pharmaceutics12010051

Xu Liu, Yongchao Su + Show 3 more

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https://doi.org/10.3390/pharmaceutics12010051

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Abstract

Clay–polymer nanocomposites have exhibited a great potential as carriers for controlled release drug delivery. This study aims to prepare exfoliated montmorillonite–Eudragit RS nanocomposites using reactive melt extrusion and investigate the influence of claying loading, clay types (sodium montmorillonite (Cloisite Na) vs. organomodified montmorillonite (Cloisite 20)) on clay–polymer interactions and drug release properties. The clays were used as the filler material at various levels in Eudragit RS and theophylline was used as the active pharmaceutical ingredient. The resulting structure of the nanocomposites was characterized using TEM (transmission electron microscopy) and XRPD (X-ray powder diffraction). The hygroscopicity of the nanocomposites was investigated using DVS (dynamic vapor sorption). The effect of the interfacial interaction between the polymer and clay sheet, the clay loading as well as the clay type on the drug release behavior were further studied by dissolution testing. TEM and XRPD data show that when the clay content is increased from 5% to 15% by weight, the nanocomposite’s structure switches from a fully exfoliated state to intercalated structures or partial exfoliation with stacked clay layers. FT-IR (fourier transform infrared spectroscopy) and ssNMR (solid-state NMR) results suggest that Cloisite Na and Cloisite 20 layers exhibit different interaction strengths with polymer networks by creating compacted complex structures. The addition of nanoclay in the formulation could robustly adjust drug release profiles, and the clay concentration and type are important factors that affect the crossing-linking density of the nanocomposites by adjusting the drug release properties. This study indicates that the clay–Eudragit RS nanocomposites provide an improved oral controlled drug delivery system that minimizes the drug dosing frequency, potentially leading to improved patient compliance.

Highlights

Oral controlled drug delivery systems are a recognized protocol to prepare materials that can effectively encapsulate drug molecules and release them at the target site for a defined period of time and in a controlled manner
The results show that the properties of the Cloisite 20 nanocomposites exceeded the neat PMMA and PMMA/Cloisite Na microcomposites, which is attributed to the formation of more a favorable polymer–filler interaction
The study has demonstrated that both Cloisite Na and Cloisite 20 could be exfoliated in Eudragit RS through hot melt extrusion

Summary

Introduction

Oral controlled drug delivery systems are a recognized protocol to prepare materials that can effectively encapsulate drug molecules and release them at the target site for a defined period of time and in a controlled manner. In addition to improving the drug efficacy, specificity, therapeutic index and tolerability of corresponding drugs, oral controlled drug delivery systems can reduce the patient expenses as well as the risks of toxicity [1,2]. Because of their multiple and unique advantages, oral controlled drug delivery systems have attracted intense interest from pharmaceutical scientists and formulators for over four decades. Hot-melt extrusion (HME) of biodegradable polymers with API, for controlling or modifying the drug release, has received increased attention in the pharmaceutical literature in recent years [6,7]. The molecular level mixing allows close contact between API and excipients at high frequencies This makes HME an ideal process for the solid-state chemical reaction. We utilize RME to prepare clay–polymer nanocomposites for sustained drug release

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