Cassava starch as modified release excipient in selected gliclazide oral dosage forms

Abstract

Solid oral dosage forms are still the most leading delivery system employed commercially due to the ease in which it can be handled, administered and even transported. Several varieties of solid oral dosage forms are commercially available which include different types of tablets, capsules, multi-unit particulate systems as well as medicated lozenges. Different designs and manufacturing methods are used for solid oral dosage forms resulting in different release mechanisms. Drug release is an important consideration during dosage form design especially for drugs with short half-lives. These types of drugs require regularly timed dosing intervals. More dose intervals can impede the adherence to therapy, because patients might forget a dose. The lack in adherence adversely affects the treatment protocol necessary for the management of disease. To overcome adversities and to modify drug release, various methods can be employed in order to provide a desirable therapeutic product, including alternative manufacturing methods and the addition of specialised excipients. One of the most promising manufacturing methods to date regarding modified release, whether sustained, controlled or multi-dose release, is the production of pharmaceutical pellets, more commonly known as beads. Several methods can be employed in order to produce beads. For this study it was opted to use a method, which has extensively been researched since the 1950s known as extrusion-spheronisation. Starches and starch based products have been utilised for many years as multifunctional excipients in the production of solid oral dosage forms. For instance, starches have been used as fillers, binders and disintegrants. The polymer rich matrix of a starch makes it highly versatile in these applications. Furthermore, the low cost involved in manufacturing or sourcing starch and starch based products, also makes it a commercially viable alternative to other market available excipients which might be more expensive. Cassava is one of the world’s most predominant sources of starch. It is globally grown and sourced in sub-tropic environments. Being a sustainable product which produces a high yield of starch, this study investigated the applicability of cassava starch as a filler in bead formulations using gliclazide as model drug. Physical characteristics and flowability of cassava starch were evaluated with various methods, which included thermo-analysis, moisture content, infrared spectrometry, and flow properties. Beads were evaluated in order to determine whether extrusion-spheronisation improved the flow of the starch. The physical characteristics such as friability, swelling and erosion, and disintegration were also evaluated. Dissolution testing and analysis provided profiles which were assessed and compared to a commercially available product, Diamicron®. It was evident from the study that cassava is not the ideal filler to include in the manufacture of beads, even though a single cassava bead formulation did provide prolonged release of the drug over a 12 h period. Approximately 60% of the drug was pharmaceutically available within the first 30 min of dissolution assessment and the remaining 40% dissolved slowly over the remaining duration of the study. The dissolution profile obtained for this particular formulation correlated with the arbitrary release profile of sustained drug release. It could therefore be concluded that a product could indeed be produced which may be a viable candidate as a commercially substitute for the current commercially available product, in terms of cost-effectiveness and sustainability. From the study it was also evident that Avicel® provided a better prolonged release profile in terms of mean dissolution time. Avicel® formulations proved to render the most similar release profiles to that of the reference product, Diamicron®.