• International Journal of Technology (IJTech)
  • Vol 11, No 5 (2020)

Tablet Formulation Containing Chitosan-Alginate Microparticles: Characterization and Release Profile of Xanthones

Tablet Formulation Containing Chitosan-Alginate Microparticles: Characterization and Release Profile of Xanthones

Title: Tablet Formulation Containing Chitosan-Alginate Microparticles: Characterization and Release Profile of Xanthones
Elsa Anisa Krisanti, David Lazuardi, Kianti Kasya Kiresya, Kamarza Mulia

Corresponding email:


Cite this article as:
Krisanti, E.A., Lazuardi, D., Kiresya, K.K., Mulia, K., 2020. Tablet Formulation Containing Chitosan-Alginate Microparticles: Characterization and Release Profile of Xanthones. International Journal of Technology. Volume 11(5), pp. 900-909

197
Downloads
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
Kamarza Mulia Chemical Engineering Department, Faculty of Engineering, Universitas Indonesia, Depok 16424, Indonesia
Email to Corresponding Author

Abstract
Tablet Formulation Containing Chitosan-Alginate Microparticles: Characterization and Release Profile of Xanthones

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

Introduction

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)

?-mangostin

?-mangostin

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.



Conclusion

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.

Acknowledgement

The research activity was part of the LPDP Rispro Invitasi 2019 UI SK KEP-52/LPDP/2019 .

Supplementary Material
FilenameDescription
R2-CE-4338-20201020222531.jpg ---
R2-CE-4338-20201020222555.jpg ---
R2-CE-4338-20201020222607.jpg ---
References

Abruzzo, A., Bigucci, F., Cerchiara, T., Saladini, B., Gallucci, M.C., Cruciani, F., Vitali, B., Luppi, B., 2013. Chitosan/Alginate Complexes for Vaginal Delivery of Chlorhexidine Digluconate. Carbohydrate Polymers, Volume 91(2), pp. 651658

Ahmad, M., Yamin, B.M., Lazim, A.M., 2012. Preliminary Study on Dispersion of ?-Mangostin in the PNIPAM Microgel System. The Malaysian Journal of Analytical Sciences, Volume 16(3), pp. 256261

Aisha, A.F.A., Abu-Salah, K.M., Ismail, Z., Majid, A.M.S.A., 2013. Determination of Total Xanthones in Garcinia mangostana Fruit Rind Extract by UV Spectrophotometry. Journal of Medicinal Plants Research, Volume 7(1), pp.  2935

Aisha, A.F.A., Abu-Salah, K.M., Siddiqui, M.J., Ismail, Z.A., Majid, M.S.A., 2012a. Quantification of ?-, ?- and ?-Mangostin in Garcinia mangostana Fruit Rind Extracts by a Reverse Phase High Performance Liquid Chromatography. Journal of Medicinal Plants Research, Volume 6(29), pp. 45264534

Aisha, A.F.A., Ismail, Z., Abu-Salah, K.M., Majid, A.M.S.A., 2012b. Solid Dispersions of ?-Mangostin Improve Its Aqueous Solubility through Self-assembly of Nanomicelles. Journal of Pharmaceutical Sciences, Volume 101(2), pp. 815825

Al-Massarni, S.M., El Gamal, A.A., Al-Musayeib, N.M., Mothana, R.A., Basudan, O.A., Al-Rehaily, A.J., Farag, M., Assaf, M.H., El Tahir, K.E.H., Maes, L., 2013. Phytochemical, Antimicrobial and Antiprotozoal Evaluation of Garcinia mangostana Pericarp and ?-Mangostin, Its Major Xanthone Derivative. Molecules, Volume 18(9), pp. 1059910608

Ansel, H.C., Allen Jr, L.V., Popovich, N.G., 1999. Pharmaceutical Dosage Forms and Drug Delivery Systems. 60-62, Lippincott Williams and Wilkins, Philadelphia, PA. USA

Chaovanalikit, A., Mngmuang, A., Kitbunluewit, T., Choldumrongkool, N., Sondee, J., Chupratum, S., 2012. Anthocyanins and Total Phenolics Content of Mangosteen and Effect of Processing on the Quality of Mangosteen Products. International Food Research Journal, Volume 19(3), pp. 10471053

Genoux-Bastide, E., Lorendeau, D., Nicolle, E., Yahiaoui, S., Magnard, S., Di?Pietro, A., Baubichon-Cortay, H., Boumendjel, A., 2011. Identification of Xanthones as Selective Killers of Cancer Cells Overexpressing the ABC Transporter MRP1. ChemMedChem, Volume 6(8), pp. 14781484

Jung, H., Su, B., Keller, W., Mehta, R., Kinghorn, A., 2006. Antioxidant Xanthones from the Pericarp of Garcinia mangostana (Mangosteen). Journal of Agricultural and Food Chemistry, Volume 54(6), pp. 20772082

Krisanti, E., Aryani, S.D., Mulia, K., 2017. Effect of Chitosan Molecular Weight and Composition on Mucoadhesive Properties of Mangostin-loaded Chitosan-Alginate Microparticles. In: AIP Conference Proceedings, Volume 1817(1), pp. 020014

Kumar, T.M., Paul, W., Sharma, C.P., Kuriachan, M.A., 2005. Bioadhesive, pH Responsive Micromatrix for Oral Delivery of Insulin. Trends in Biomaterials & Artificial Organs, Volume 18(2), pp. 198202 

Lachman, L., Lieberman, H.A., Kanig, J.L., 1986. The Theory and Practice of Industrial Pharmacy. 3rd Ed. Lea & Febiger, Philadelphia, PA 19106. USA 

Lotfipour, F., Nokhodchi, A., Saeedi, M., Norouzi-Sani, S., Sharbafi, J., Siahi-Shadbad, M.R., 2004. The Effect of Hydrophilic and Lipophilic Polymers and Fillers on the Release Rate of Atenolol from HPMC Matrices. Il Farmaco, Volume 59(10), pp. 819825

Mulia, K., Krisanti, E., Terahadi, F., Putri, S., 2015. Selected Natural Deep Eutectic Solvents for the Extraction of ?-Mangostin from Mangosteen (Garcinia mangostana L.) Pericarp. International Journal of Technology, Volume 6(7), pp. 12111220

Mulia, K., Rachman, D., Krisanti, E.A., 2019. Preparation, Characterization and Release Profile of Chitosan Alginate Freeze Dried Matrices Loaded with Mangostins. Journal of Physics: Conference Series. Volume 1295, pp. 1–9

Mulia, K., Singarimbun, A.C., Krisanti, E.A., 2020. Optimization of Chitosan–Alginate Microparticles for Delivery of Mangostins to the Colon Area using Box–Behnken Experimental Design. International Journal of Molecular Science, Volume 21(3), pp. 873–882

Nicoletti, M., 2012. Nutraceuticals and Botanicals: Overview and Perspectives. International Journal of Food Sciences and Nutrition, Volume 63(S1), pp. 26

Palakawong, C., Sophanodora, P., Pisuchpen, S., Phongpaichit, S., 2010. Antioxidant and Antimicrobial Activities of Crude Extract from Mangosteen (Garcinia mangostana L.) Parts and Some Essential Oils. International Food Research Journal, Volume 17(3), pp. 583589

Pedraza-Chaverri, J., Cárdenas-Rodríguez, N., Orozco-Ibarra, M., Pérez- Rojas, J.M., 2008. Medicinal Properties of Mangosteen (Garcinia mangostana). Food and Chemical Toxicology, Volume 46 (10), pp. 32273239

Peerapattana, J., Otsuka, K., Otsuka, M., 2013. Application of NIR Spectroscopy for the Quality Control of Mangosteen Pericarp Powder: Quantitative Analysis of Alpha-Mangostin in Mangosteen Pericarp Powder and Capsule. Journal of Natural Medicines, Volume 67(3), pp. 452-459

Sah, M.L., Juyal, V., 2012. Programmed Delivery of Verapamil Hydrochloride from Tablet in a Capsule Device. Brazilian Journal of Pharmaceutical Sciences, Volume 48(2), pp. 237242

Sinha, V., Singla, A., Wadhawan, S., Kaushik, R., Kumria, R., Bansal, K., Dhawan, S., 2004. Chitosan Microspheres as a Potential Carrier for Drugs. International Journal of Pharmaceutics, Volume 274(1-2), pp. 133

Tamat, S.R., Rahman, E., Kardono, L.B., 2014. Formulation of Tablets Containing Extracts of Soursop Leaves, Mangosteen Rind, Ling Zhi Mushroom and its Antioxidant and Immunomodulator Activity Tests. Jurnal Ilmu Kefarmasian Indonesia, Volume 12(1), pp. 124138

Tonnesen, H.H., Karlsen, J., 2002. Alginate in Drug Delivery System. Drug Development and Industrial Pharmacy, Volume 28(6), pp. 621630

Wathoni, N., Yuniarsih, N., Cahyanto, A., Muhctaridi, M., 2019. ?-Mangostin Hydrogel Film Based Chitosan–Alginate for Recurrent Aphthous Stomatitis. Applied Science, Volume 9(23), pp. 5235–5248

Widowati, W., Rusmana, D., Hardiman, H., Tiono, H., Wargasetia, T.L., Pujimulyani, D., 2013. Mangosteen Peel (Garcinia mangostana L.) Extract for Effervescent Tablet. Proc. World Academy of Science, Engineering and Technology, Volume 82, pp. 190195

Yu, C., Yin, B., Zhang, W., Cheng, S., Zhang, X., Zhuo, R., 2009. Composite Microparticle Drug Delivery Systems based on Chitosan, Alginate, and Pectin with Improved pH-Sensitive Drug Release Property. Colloids and Surfaces B: Biointerfaces, Volume 68(2), pp. 245249