Design and Evaluation of Hydroxypropyl Methylcellulose Matrix Tablets for Oral Controlled Release: A Historical Perspective

Hydrophilic matrix tablets (matrices) for oral use are designed to hydrate on swallowing, and form a ‘gel’ layer of hydrated polymer at the tablet surface to control the rate of drug release during passage of the matrix through the gastrointestinal tract. During gastrointestinal transit, the matrices are reduced in size through surface erosion and dissolution. This reduces the probability of expulsion of an exhausted ‘ghost’ matrix sometimes seen with earlier hydrophobic matrices, such as those based on fatty acids, waxes or ethylcellulose [1, 2]. Hydrophilic matrices release their drug content slowly, and their therapeutic effect is prolonged. However, in order to ensure a reproducible action on the body it is imperative that (1) the matrix remains intact and (2) the drug is released at a controlled rate. During gastrointestinal transit, hydrophilic matrices are subjected to a range of shear forces such as peristalsis, and they also encounter a variety of pH and chemical environments. In poorly formulated systems, these mechanical and chemical challenges can potentially cause the matrix to prematurely lose its integrity and break up [3]. The concept of using a water-swellable, non-cross-linked ‘hydrophilic’ polymer to control the release of drug from an oral matrix tablet was promoted in the 1960s. Thereafter, extensive studies have led to the development of a multitude of commercially marketed, oral drug delivery products which utilise the ‘hydrophilic matrix’ concept. Such products are generally matrices comprising a compressed powder, a mixture of drug and excipients with at least one hydrophilic polymer.