Elsevier

European Polymer Journal

Volume 45, Issue 6, June 2009, Pages 1765-1776
European Polymer Journal

Synthesis and characterization of new copolymers of ethyl methacrylate grafted on tapioca starch as novel excipients for direct compression matrix tablets

https://doi.org/10.1016/j.eurpolymj.2009.02.019Get rights and content

Abstract

In last years, the introduction of new materials for drug delivery matrix tablets has become more important. This paper evaluates the physicochemical and mechanical properties of new graft copolymers of ethyl methacrylate (EMA) on tapioca starch (TS) and hydroxypropylstarch (THS), synthesized by free radical polymerization and dried in a vacuum oven (OD) or freeze–dried (FD). Infrared and 13C NMR spectroscopies confirm the change of chemical structure of the copolymers and X-ray diffraction shows up the higher amorphization of copolymers respect to the carbohydrates. Particle size analysis and SEM indicate that graft copolymerization leads to an increase of particle size and a more irregular shape. Graft copolymerization implies decrease of density and moisture content values. Heckel equation shows that copolymers have less densification by particle rearrangement and fragmentation than carbohydrates. Concerning the drying methods, FD products have larger plasticity and lower elasticity than OD copolymers. Graft copolymerization produces a decrease of the applied pressure necessary to obtain tablets, ejection force and friction work. Furthermore, graft copolymers show longer disintegration time than tablets from raw starches. These qualities suggest that these copolymers could be used as excipients in matrix tablets obtained by direct compression, and with a potential use in controlled release.

Introduction

Monolithic devices or matrices represent a substantial part of the drug delivery systems. In pharmaceutical industry, the matrices for oral administration are commonly manufactured as tablets by direct compression [1]. However, it is well known that direct compression is possible only for a limited number of substances. Many of the materials widely used for tablet formulation are difficult to compress because of their elastic compression behaviour and poor flow properties [2].

In the last years, the introduction of new materials for drug delivery devices has become more important. Among these, synthetic and some natural polymers have been used and their production has grown in great extent. Starch is an abundant, inexpensive, natural biopolymer that can be metabolised by the human body. Moreover, it is relatively inert and does not react with many active drug substances. These favourable properties promote its applications for the production of pharmaceuticals [3], [4], [5], [6]. However, starches possess poor flow properties and undergo elastic deformation during the tableting process [7]. In contrast, starch can be easily modified with a variety of useful monomeric and polymeric products by physical and chemical means. Graft copolymerization of synthetic polymers onto a polysaccharide backbone offers one of the best ways to get new copolysaccharides with enhanced properties for important applications [8], [9]. Thus, polyacrylics occupy a significant position as grafted polymers [10].

Recently, a new generation of graft copolymers combining semi-synthetic (cellulose and potato starch derivatives) and synthetic (methyl methacrylate) polymers has been introduced [11], [12], [13], [14]. However, it was probed that depending on the type of carbohydrate and monomer used, the properties of the copolymer will be different [9], and consequently, may not have identical properties as excipients in tablet preparations. There is still a wide range of acrylic monomers and natural polymers that can be tested. While in Europe potato starch is widely used, in most tropical countries there are many other sources for starch, which can be used in tableting. Commonly grown starch-containing plants are maize, rice, and tapioca or cassava [15].

Native tapioca starch possesses many desiderable filler properties but it has poor flowability and compressibility [16]. The latter two parameters have a particular importance for direct compression tablets [15], [17]. Furthermore, the filler should yield tablets of adequate crushing strength without having to apply an excessive compression force [18], [19]. Atichokudomchai et al. [17] have modified native tapioca starch showing that these new products were useful as filler in direct compression tablet preparation. Due to the good results obtained with the described materials, we estimate of interest to synthesize and characterize new graft copolymers derived from tapioca starch and hydroxypropyl tapioca starch in order to evaluate its usefulness in direct compression matrix tablets. The chosen monomer for grafting is ethyl methacrylate (EMA), a synthetic monomer that gives rise to biocompatible and non toxic acrylic polymers and possesses hydrophobic character and can be easily polymerized [20], [21]. A comparison among these new graft copolymers and the native starches, used as received, will be made. This paper also evaluates the effect of the carbohydrate nature and drying process (vacuum oven and freeze–dried) on the physico-chemical and mechanical properties of the powdered materials as well as the porous structure of the tablets obtained from the new copolymers.

Section snippets

Materials

Tapioca starch (TS) (Tapioca Starch, batch MCB 3053) (±17% of amylose) and hydroxypropyl tapioca starch (THS) (Tapioca Textra, Batch KCB 8010) were kindly supplied by National Starch & Chemical (Manchester, UK) as natural and semi-synthetic polymers. Ethyl methacrylate (EMA) (Merck, Hohenbrunn, Germany) was chosen as acrylic monomer for graft copolymerization.

All the reagents used for the synthetic process were of analytical grade.

Before use, the materials were stored at constant relative

Synthesis of graft copolymers and grafting yields

In order to study the efficiency of the graft copolymerization reaction, the poly-ethylmethacrylate homopolymer (PEMA) was removed from the total reaction product, with tetrahydrofuran (THF), by soxhlet extraction. PEMA homopolymer is the only product that could be solubilized by THF from the medium. In that way, PEMA homopolymer was isolated and quantified after evaporation of the solvent. The remaining graft copolymer (the insoluble fraction) was hydrolyzed in acid medium, to give the PEMA

Conclusions

It can be concluded that grafting of EMA on carbohydrate backbone causes important modifications on the physicochemical and technological properties of tapioca and hydroxypropyl tapioca starches. The reaction yields obtained when grafting EMA on tapioca starch and hydroxypropyl tapioca starch are high (over 93%) and exhibit low relative standard deviation values, which confirm the reproducibility of the synthesis.

The copolymer composition was accurately estimated, with 30–40% of carbohydrate

Acknowledgements

This work has been supported by a FPU grant from the Spanish Government and is part of a project (MAT2004-01599) from Spanish Ministry of Science and Technology.

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