Abstract
Besides its poor dissolution in polymers, the stability, and bitterness of (-)-epicatechin present challenges for additional developments. Polymer formulations rich in flavonoids or other antioxidants can be developed by hot melt extrusion (HME) for enhancement of stability, release, and taste masking. The formulations are extruded at a temperature substantially below the melting point of (-)-epicatechin to avoid its degradation. The corresponding compound consists of about 50% wt. of an active nutraceutical ingredient, in this case (-)-epicatechin, and food grade polymers (GRAS: generally recognized as safe). In order to identify possible chemical or physical changes in the formulations, they were characterized using various techniques, such as differential scanning calorimetry, thermogravimetric analysis, polarized optical microscopy, in vitro release profile, sensory analysis, high-performance liquid chromatography, and Fourier transform infrared spectroscopy. The crystallinity of (-)-epicatechin was reduced after melt extrusion, but its chemical structure remained unchanged. The main contribution of this research is to shed light on the preparation of polymeric formulations based on (-)-epicatechin using HME as an encapsulation technique to improve stability, release, and taste masking, which may be scaled up and commercially launched as nutraceutical products.
Abbreviations
- AI
active ingredient
- AN7
Aqualon™ EC N7 Pharm
- BMM
batch melt mixing
- DSC
differential scanning calorimetry
- EC
(-)-epicatechin
- ES10
Ethocel™ Standard 10 Premium
- FC
film casting
- FTIR
Fourier transform infrared spectroscopy
- HME
hot melt extrusion
- HPLC
high-performance liquid chromatography
- KSR
Kollidon® SR
- L100
Eudragit® L 100
- PF
polymer formulations
- PF1
polymer formulation 1 (50%wt. EC, 30%wt. AN7, 10%wt. KSR, 10%wt. L100)
- PF2
polymer formulation 2 (50%wt. EC, 30%wt. ES10, 10%wt. KSR, 10%wt. L100)
- PF1-BMM
polymer formulation 1 processed by batch melt mixer
- PF2-BMM
polymer formulation 2 processed by batch melt mixer
- PF1-HME
polymer formulation 1 processed by hot melt extrusion
- PF1-PM
polymer formulation 1 in physical mixture
- PM
physical mixture
- POM
polarized light optical microscopy
- TGA
thermal gravimetric analysis
- Tg
glass transition temperature
- Tm
melting point
- TM
Melt Temperature
- ΔHm
heat of fusion
Acknowledgments
The authors would like to thank for the technical support of the professionals from the Instituto de Capacitación e Investigación del Plástico y del Caucho – ICIPC. Charlie Martin and Leistritz are acknowledged for the loan of a pharmaceutical twin screw extruder (Nano 16). Ashland, DOW, BASF, and EVONIK are gratefully acknowledged for the donation of polymeric excipients. The authors acknowledge the use of the services and infrastructure of Universidad EAFIT, Universidad de Antioquia, and ICIPC. Universidad EAFIT is gratefully acknowledged by the 50% grant of Chem. Catalina Álvarez in the Master in Engineering Program.
Funding: The authors acknowledge the financial support of Colciencias, ICIPC, Vidarium, and Compañía Nacional de Chocolates. Departamento Administrativo de Ciencia, Tecnología e Innovación, funder id: http://dx.doi.org/10.13039/100007637, grant number: FP44842-240-2016.
Conflict of interest statement: The authors declare no conflict of interests.
References
[1] Rashidinejada A, Bircha J, Sun-Waterhousec D, Everettb D. Food Bioprod. Process. 2016, 100, 238–245.10.1016/j.fbp.2016.07.005Search in Google Scholar
[2] Gadkaria P, Balaraman M. Food Bioprod. Process. 2015, 93, 122–138.10.1016/j.fbp.2013.12.004Search in Google Scholar
[3] Hodgson J, Croft K. Mol. Aspects Med. 2010, 31, 495–502.10.1016/j.mam.2010.09.004Search in Google Scholar PubMed
[4] Khan N, Mukhtar H. Life Sci. 2007, 81, 519–533.10.1016/j.lfs.2007.06.011Search in Google Scholar PubMed PubMed Central
[5] Schroeter H, Heiss C, Spencer JP, Keen CL, Lupton JR, Schmitz HH. Mol. Aspects Med. 2010, 31, 546–557.10.1016/j.mam.2010.09.008Search in Google Scholar PubMed
[6] Arts ICW, Hollman PCH, Feskens EJM, Bueno de Mesquita HB, Kromhout D. Eur. J. Clin. Nutr. 2001, 55, 76–81.10.1038/sj.ejcn.1601115Search in Google Scholar PubMed
[7] Panga J, Zhanga Z, Zhengb T, Bassigb B, Gec J, Yangd Y, Huange D, Baia M, Peng Y. Int. J. Cardiol. 2016, 202, 967–974.10.1016/j.ijcard.2014.12.176Search in Google Scholar PubMed
[8] Arts ICW, Hollman PCH. Am. J. Clin. Nutr. 2005, 81, 317S–325S.10.1093/ajcn/81.1.317SSearch in Google Scholar PubMed
[9] Ananingsih V, Sharma A, Zhou W. Food Res. Int. 2013, 50, 469–479.10.1016/j.foodres.2011.03.004Search in Google Scholar
[10] Rodrigues CF, Ascenção K, Silva FA, Sarmento B, Oliveira MB, Andrade JC. Curr. Med. Chem. 2013, 20, 4744–4757.10.2174/09298673113209990158Search in Google Scholar PubMed
[11] Janeiro P, Oliveira Brett AM. Anal. Chim. Acta 2004, 518, 109–115.10.1016/j.aca.2004.05.038Search in Google Scholar
[12] Mochizuki M, Yamazaki SI, Kano K, Ikeda T. Biochim. Biophys. Acta 2002, 1569, 35–44.10.1016/S0304-4165(01)00230-6Search in Google Scholar
[13] Andrew R, Izzo A. Br. J. Pharmacol. 2017, 174, 1177–1194.10.1111/bph.13779Search in Google Scholar PubMed PubMed Central
[14] Boye JI. Nutraceutical and Functional Food Processing Technology, John Wiley & Sons, Ltd.: Chichester, 2015.10.1002/9781118504956Search in Google Scholar
[15] Hodgson JM. Clin. Exp. Pharmacol. Physiol. 2006, 33, 838–841.10.1111/j.1440-1681.2006.04450.xSearch in Google Scholar PubMed
[16] Scalbert A, Williamson G. J. Nutr. 2000, 130, 2073–2085.Search in Google Scholar
[17] Dower JI, Geleijnse JM, Hollman P, Soedamah-Muthu SS, Kromhout D. Am. J. Clin. Nutr. 2016, 104, 58–64.10.3945/ajcn.115.128819Search in Google Scholar PubMed
[18] Restrepo-Uribe L, Ioannidis N, Noriega M. J. Polym. Eng. 2019, 32, 186–196.10.1515/polyeng-2018-0193Search in Google Scholar
[19] Maniruzzaman M, Boateng JS, Chowdhry BZ, Snowden MJ, Douroumis D. Drug Dev. Ind. Pharm. 2014, 40, 145–156.10.3109/03639045.2013.804833Search in Google Scholar PubMed
[20] Maniruzzaman M. Development of hot-melt extrusion as a novel technique for the formulation of oral solid dosage forms. Thesis submitted to the University of Greenwich, 2012.Search in Google Scholar
[21] Kolter K, Karl M, Gryczke A. Hot-Melt Extrusion with BASF Pharma Polymers – Extrusion Compendium. BASF The Chemical Company: Germany, 2012.Search in Google Scholar
[22] Gu L, House SE, Rooney L, Prior RL. J. Agric. Food Chem. 2008, 56, 1283–1288.10.1021/jf072742iSearch in Google Scholar PubMed
[23] Khanal RC, Howard LR, Brownmiller CR, Prior RL. J. Food Sci. 2009, 74, 52–58.Search in Google Scholar
[24] Chuah AM, Jacob B, Jie Z, Ramesh S, Mandal S, Puthan JK, Deshpande P, Vaidyanathan V, Gelling RW, Patel G, Das T, Sheeram S. Food Chem. 2014, 156, 227–233.10.1016/j.foodchem.2014.01.108Search in Google Scholar PubMed
[25] Khor CM, Ng WK, Kanaujia P, Chan KP, Dong Y. J. Microencapsul. 2017, 34, 29–37.10.1080/02652048.2017.1280095Search in Google Scholar PubMed
[26] Duvuri A. The formulation of naturally occuring polyphenolic nutraceutical agents using hot-melt extrusion. Open Access Master’s Theses. University of Rhode Island, 2011.Search in Google Scholar
[27] Estrada OA, Restrepo L, Noriega MP, Muñoz K, Alvarez CM, Mazo JC, Penagos L. Patent Cooperation Treaty (PCT), WO2018172998A, 2018.Search in Google Scholar
[28] Estrada OA, Restrepo L, Noriega MP, Muñoz K, Alvarez CM, Mazo JC, Penagos L. United States Patent and Trademark Office’s (USPTO), US20180271928A1, 2018.Search in Google Scholar
[29] Hu Y, Pan ZJ, Liao W, Li J, Gruget P, Kitts DD, Lu X. Food Chem. 2016, 202, 254–261.10.1016/j.foodchem.2016.01.130Search in Google Scholar PubMed
[30] Chowdary H, Venkaiah A, Malik S, Reddy H, Achari S, Raju P. Int. J. Innov. Pharm. Sci. Res. 2014, 5, 364–369.Search in Google Scholar
[31] Reintjes T. Solubility Enhancement with BASF Pharma Polymers: Solubilizer Compendium. BASF The Chemical Company: Germany, 2011.Search in Google Scholar
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