Development and in vitro evaluation of immediate- and sustained release Rooibos (Aspalathus linearis) preparations

Abstract

Rooibos or rooibos tea is an herbal tea made from dried leaves and stalks of the Aspalathus linearis plant that is endemic to the Cederberg Mountains in the Western Cape Province of South Africa. Rooibos is rich in polyphenols, caffeine free and low in tannins when compare to Camellia sinensis teas (Joubert et al., 2008). Many health benefits have been associated with Rooibos mainly due to the polyphenol content. These include the modulation of the bodies redox status (Kucharská et al., 2004), lipid oxidation (Marnewick et al., 2011), cancer prevention in different cancer models including skin cancer (Marnewick et al., 2005) and oesophageal cancer (Sissing et al., 2011) as well as in in vitro assays (Baba et al., 2009; Marnewick et al., 2000; Snijman et al., 2007), a reduction of risk factors for cardiovascular health (Marnewick et al., 2011; Persson et al., 2010),diabetes, inflammation reduction and modulation of metabolic processes (Beltrán-Debón et al., 2011; Marnewick et al., 2012; Schloms et al., 2012). Different methodologies are used to determine the in vitro anti-oxidant capacity of Rooibos. The Folin-Ciocalteu assay is used to determine the total polyphenols. The ferric reduction/antioxidant power assay (FRAP) and the Trolox equivalent antioxidant capacity assay (TEAC) measure the electron transfer reactions and the oxygen radical antioxidant capacity assay (ORAC) are used to measure the hydrogen transfer reactions. It has been determined that rooibos has a low bioavailability. The absorption of the Rooibos polyphenols is low (Del Rio et al., 2013) and it is rapidly eliminated from the systemic circulation (Parisi et al., 2014; Sissing et al., 2011). The poor bioavailability and the rapid elimination of Rooibos require that Rooibos should be consumed regularly during the day for optimal health benifits. Controlled release dosage forms can be used to maintain a stable drug concentration in the systemic circulation (Alderblom, 2007; Anal, 2007). The mini-tablet-in-capsule system is a versatile drug delivery system where 6 mm tablets are packed into size zero hard gelatine capsules. It allows for mini-tablets with different release profiles to be packed into the gelatine capsule to manipulate the dissolution profile i.e. a loading dose and a maintenance dose.(Li and Zhu, 2004). Different fillers were evaluated for both the immediate release and sustained release mini-tablets. Powder flow tests were performed on the excipients and the Rooibos extract to ensure reproducible tablet production. The physical properties of the mini-tablets were evaluated to ensure the tablets would fit into the gelatine capsules and would withstand the attrition during the manufacturing and packaging processes. The Rooibos extract and the mini-tablets were analysed the polyphenol content and antioxidant properties. The mini-tablet-in-capsules were subjected to a six month stability test. This study designed and produced a mini-tablet-in-capsule system that that delivered the 400 mg Rooibos polyphenols in 8 hr in an almost linear fashion. The dissolution studies revealed the dissolution followed the Korsmeyer-Peppas model. The equation was F=0.4826?t0.8572. The preliminary stability test showed the mini-tablet-in-capsule system was stable and should have at least an 24 month stability. The photograph above shows the mini-tablet-in-capsule system with ten mini-tablets filled into a size zero hard gelatine capsule. Two mini-tablets were coated white to represent the two slow release mini-tablets.