High-Amylose Sodium Carboxymethyl Starch Matrices: Development and Characterization of Tramadol Hydrochloride Sustained-Release Tablets for Oral Administration
Substituted amylose (SA) polymers were produced from high-amylose corn starch by etherification of its hydroxyl groups with chloroacetate. Amorphous high-amylose sodium carboxymethyl starch (HASCA), the resulting SA polymer, was spray-dried to obtain an excipient (SD HASCA) with optimal binding and sustained-release (SR) properties. Tablets containing different percentages of SD HASCA and tramadol hydrochloride were produced by direct compression and evaluated for dissolution. Once-daily and twice-daily SD HASCA tablets containing two common dosages of tramadol hydrochloride (100？mg and 200？mg), a freely water-soluble drug, were successfully developed. These SR formulations presented high crushing forces, which facilitate further tablet processing and handling. When exposed to both a pH gradient simulating the pH variations through the gastrointestinal tract and a 40% ethanol medium, a very rigid gel formed progressively at the surface of the tablets providing controlled drug-release properties. These properties indicated that SD HASCA was a promising and robust excipient for oral, sustained drug-release, which may possibly minimize the likelihood of dose dumping and consequent adverse effects, even in the case of coadministration with alcohol. 1. Introduction Starch is a naturally occurring and a biodegradable polymer that is metabolized by the human body. Besides being nontoxic, starch is an abundant, cost-effective, and renewable material [1]. Due to these advantages, starches and modified starches have been widely and safely used in the food industry as thickeners, enhancers, of organoleptic properties, or texture modifiers and in the pharmaceutical industry as fillers, binders, disintegrants [2], and, more recently, as hydrophilic excipients for controlled drug-release. Numerous starch-modification methods, such as chemical [3], physical (i.e., gelatinization) [4], enzymatic [5], or a combination thereof, have been employed to produce new starch products with specific properties. Starch is a good candidate for chemical reaction or transformation because it is composed of amylose and amylopectin, two glucose polymers presenting three hydroxyl groups accessible as chemically active functional entities. Some of the modifications commonly employed to prepare starch derivatives are carboxymethylation, ethoxylation, and oxidation [6]. Substituted amylose (SA) has been introduced as a promising pharmaceutical excipient for sustained drug-release. SA matrix tablets have been prepared by direct compression, which is the easiest way to manufacture an oral
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