A review of the chemical modification techniques of starch

Highlights

• Techniques for the chemical modification of starch appraised.

• Oxidation, esterification and etherification modification methods discussed.

• The implications on drug delivery systems design analyzed.

• The potential for starch-based polymer`s in drug delivery application presented.

Abstract

Starch is a naturally occurring storage copolymer with unique physicochemical properties. There are, however, some key structural properties of starch that can be modified in order to functionalize the copolymer to meet specific requirements. Specifically, the chemical modification of starch provides a variety of physicochemical benefits, some of which have been used previously to functionalize preformed drug delivery systems. Of the three main chemical modification methods reviewed (namely: oxidation, esterification and etherification), surface chemical oxidation introduces more pertinent physicochemical properties that increase overall drug delivery system efficacy and applicability. Surface oxidation evidently is the more preferable chemical modification method of pre-formed starch particles and has the greatest potential for further development when compared to the other reviewed chemical modification methods. The use of modified starch in clinical trials as well as the potential future implications of these systems is also included in this review.

Introduction

Traditionally, in oral delivery systems, excipients have been viewed as inert substances that function, amongst others, as binders, disintegrants, adhesives and sweeteners. However, in the past decade there has been a greater focus on the effects of excipients and the potential reduction of synthetic and chemical-grade agents within pharmaceutical formulation to increase patient compliance, and in some cases, the biocompatibility and efficiency of formulations (Averous, 2013; Singh, Kaur, & McCarthy, 2007). Studies have shown that excipients can in fact influence the rate and extent of drug release, in turn affecting the efficiency of the system and the absorption of the active. There is thus a great trend toward the use of natural excipients that are sometimes referred to as “herbal excipients” (Ražem & Katušin-Ražem, 2008).

The view that excipients are inert and have no effect on formulation performance has therefore changed and it is now recognized that they have a significant influence on the efficacy of the delivery system. Furthermore, there is a continued focus on natural versus synthetic excipients in formulation design. A large proportion of the excipients used are natural polymers because of their biocompatible nature, inexpensiveness and accessibility. This class of polymers is generally highly stable, hydrophilic and gel forming (Beneke, Viljoen, & Hamman, 2009). Within this class of polymers, starch is the most abundant storage polymer, found in a variety of plant organs and is widely explored in the pharmaceutical and other industries. This co-polymer consists of two macromolecular complexes: amylose and amylopectin, the proportions of which vary with botanical origin (Dimantov, Greenberg, Kesselman, & Shimoni, 2004). Amylose, a linear polysaccharide of glucose units linked through α-1-4 glycosidic bonds, on average accounts for 20–30% of starch composition (Dimantov et al., 2004). Amylopectin, the more branched macromolecular component, has additional α-1-6 links and accounts for 70–80% of starch composition (Tharanathan, 2005).

The pharmaceutical application of starch and other polymers in drug delivery is mostly applicable in the matrix-assisted system approach. In this approach, a drug is dispersed in a porous matrix network that is either swellable and/or non-swellable and is released in response to stimuli such as pH, charge or enzymatic reaction (Huang & Brazel, 2001). The primary objective of such systems are the provision of controlled drug release mechanisms that reduce oscillations of drug concentrations in the blood, thus maintaining drug plasma concentrations within an optimal range required for therapeutic action (Huang and Brazel, 2001, Nabais et al., 2007). This both maximizes the efficacy of the drug and reduces dosage related side effects in some formulations (Pal, Singhal, & Kulkarni, 2002).

In order to maximize the application of starch in drug delivery and other industries, the physiochemical and physicomechanical properties can be tailored to fit the required properties of the produced system. There are four basic types of starch modifications, namely; chemical, physical, enzymatic and genetic, all of which target the three available hydroxyl groups of the starch co-polymer (Fig. 1). Chemical modification is the most widely explored modification method due to the non-destructive nature of a select few of the processes and potential increases in the functionality of the modified starch. Modification thus enables enhancement and/or introduction of key properties that may be required for specific pharmaceutical applications (Jamzad, Tutunji, & Fassihi, 2005). The three available hydroxyl groups (at position: C2, C3 and C6) can be chemically modified through esterification, etherification and oxidation (Khan & Ahmad, 2013). The degree of modification of the three available groups typically varies with the genetic origin of the starch and the reaction conditions (Pu et al., 2011). Such modifications in native starch alter the gelatinization, swelling, solubility properties, pasting and retrogradation characteristics (Tharanathan, 2005). These newly formed properties therefore allows for the modified starch matrices to be functionalized for pharmaceutical applications with more appreciable physicochemical and biodegradation properties when compared to its native form. This article therefore reviews the chemical modification methods utilized in the preparation and synthesis of modified starch co-polymers with emphasis given to their applications in drug delivery system design and formulation, which has not been notably reviewed previously.