|Elsa Anisa Krisanti||Chemical Engineering Department, Faculty of Engineering, Universitas Indonesia, Depok 16424, Indonesia|
|David Lazuardi||Chemical Engineering Department, Faculty of Engineering, Universitas Indonesia, Depok 16424, Indonesia|
|Kianti Kasya Kiresya||Chemical Engineering Department, Faculty of Engineering, Universitas Indonesia, Depok 16424, Indonesia|
Mangosteen pericarp extract contains a high amount of xanthones, which are secondary plant metabolites that exhibit high antioxidant activities as well as beneficial pharmacological properties, but low bioavailabilities. In this study, xanthones extracted from the pericarp of soursop fruit were encapsulated in chitosan-alginate microparticles by ionic gelation, and the microparticles were subsequently formulated into antioxidant supplement tablets by direct compression. One of the tablet formulations satisfied the requirements for weight and size uniformity as well as friability, but not hardness. Dissolution test results revealed similar release profiles characterized by a burst release that occurs in the first 60 min of immersion in simulated gastrointestinal fluids and a complete release of xanthones in 120 min. The results obtained herein demonstrated the potential of the tested tablet formulations for the delivery of xanthones into the gastrointestinal tract. If a targeted release to a specific area in the gastrointestinal tract is desirable, the composition of the excipients in the present formulation should be modified.
Alginate; Chitosan; Mangosteen; Mangostin; Xanthone
od supplements are food products intended to complement a diet with vitamins, minerals, or other substances in concentrated amounts that exert physiological effects (Nicoletti, 2012). Antioxidant compounds present in food supplements reduce the incidence of chronic diseases caused by free radicals in the body, such as cancer, brain dysfunction and heart disease. Although the body can produce antioxidants from cell metabolism, the additional intake of antioxidants is required as the number of free radicals increases.
Meanwhile, the pericarp of mangosteen fruit (Garcinia mangostana L.) contains bioactive compounds known as xanthones, which exhibit high antioxidant activities (Jung et al., 2006; Palakawong et al., 2010; Chaovanalikit et al., 2012), and ?-mangostin and ?-mangostin are the main derivatives of xanthones (Al-Massarni et al., 2013; Mulia et al., 2015). Figure 1 shows their molecular structures. Mangostins have been reported to exhibit cytotoxic effects, with the ability to induce the apoptosis of cancer cells and to selectively kill cancer cells (Pedraza-Chaverri et al., 2008; Genoux-Bastide et al., 2011).
Owing to its biodegradable, non-toxic and mucoadhesive properties, chitosan is an extensively investigated biopolymer for drug delivery. It has been used in controlled-release oral formulations to increase the bioavailability of easily degraded drugs and bioactive compounds such as antibiotics, anticancer agents, proteins, peptides and vaccines (Sinha et al., 2004).
Figure 1 Molecular structures of ?-mangostin and ?-mangostin
Alginate is another biodegradable and non-toxic polymer typically used in drug formulations and as a food additive (Tonnesen and Karlsen, 2002). In contrast to chitosan, alginate exhibits stable properties under an acidic pH in the stomach, while it undergoes swelling and dissolution at a more neutral pH in the intestine (Kumar et al., 2005). A tablet is the most commonly used oral formulation for the delivery of drugs into the gastrointestinal tract, comprising active substances and excipients such as diluents, binders, lubricants, crushing agents, coatings, flavoring ingredients and other additives (Ansel et al., 1999). Direct compression is employed to manufacture tablets via the direct compression of a mixture of active substances and dry excipients without prior treatment.
Xanthones, often reported as a-mangostin, have been encapsulated in various chitosan-alginate formulations including powder in a capsule (Peerapattana et al., 2013), microparticles (Krisanti et al., 2017; Mulia et al., 2020), effervescent tablets (Widowati et al., 2013), dispersion in a microgel (Ahmad et al., 2012), tablets (Tamat et al., 2014), hydrogel films (Wathoni et al., 2019) and freeze-dried matrices (Mulia et al., 2019). Recently, the optimization of chitosan-alginate microparticles by using the Box–Behnken experimental design confirmed that alginate is a suitable biopolymer to complement chitosan for the delivery of mangostin to the colon area (Mulia et al., 2020). For further investigation, tablet formulations of microparticles as an antioxidant supplement were prepared and tested. In this study, physicochemical characteristics of tablet formulations of xanthone-loaded chitosan-alginate microparticles (including dissolution, hardness and friability tests), as well as the release profile of xanthones in simulated gastrointestinal fluids, were investigated.
Xanthone-loaded chitosan-alginate microparticles in a tablet formulation were evaluated in terms of their physicochemical characteristics and release profiles in simulated gastrointestinal fluids. The two tablet formulations satisfied the requirements for weight and size uniformity, but not for hardness; only one formula satisfied the friability requirement. The dissolution test using three simulated gastrointestinal fluids revealed similar pH-independent cumulative release profiles of mangostin. All simulated gastrointestinal fluids exhibited burst releases in the first 60 min of the immersion time. The results obtained herein demonstrated the potential of the tested tablet formulations for the delivery of xanthones into the gastrointestinal tract. To achieve the release to a targeted area in the digestive tract, the excipient composition of the tablet should be modified.
The research activity was part of the LPDP Rispro Invitasi 2019 UI SK KEP-52/LPDP/2019 .
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