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Development of probiotic tablet using alginate, pectin, and cellulose nanocrystals as excipients

Abstract

The objective of this study is to develop a probiotic tablet formulation based on alginate, pectin, and cellulose nanocrystals (CNC) that can preserve high viability of a probiotic bacterium, Lactobacillus rhamnosus ATCC 9595, in gastrointestinal media as well as during storage. A central composite design including three independent biopolymeric material factors (alginate, pectin, and CNC) was applied, and 18 tablet formulations containing probiotic cells were formed. The optimized probiotic tablet based on alginate, pectin, and CNC showed 84 % cell viability after sequential transition through gastrointestinal media, whereas probiotic tablets prepared with alginate, pectin, and CNC individually showed only 19, 17, and 10 % probiotic viability, respectively. Swelling study also revealed that the optimized tablet underwent less dissolution in gastric solution (pH 1.5) and continuous dissolution in intestinal solution (pH 7). The optimized probiotic tablet was stored at 25 and 4 °C for up to 42 days, revealing a reduction of only 0.4 and 0.2 log colony forming units (CFU)/tablet, respectively, after 42 days.

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References

  • Adjallé KD, Vu KD, Tyagi RD, Brar SK, Valéro JR, Surampalli RY (2011) Optimization of spray drying process for Bacillus thuringiensis fermented wastewater and wastewater sludge. Bioprocess Biosyst Eng 34:237–246

    Article  Google Scholar 

  • Ahrabi SF, Madsen G, Dyrstad K, Sande SA, Graffner C (2000) Development of pectin matrix tablets for colonic delivery of model drug ropivacaine. Eur J Pharm Sci 10:43–52

    CAS  Article  Google Scholar 

  • Alexandrescu L, Syverud K, Gatti A, Chinga-Carrasco G (2013) Cytotoxicity tests of cellulose nanofibril-based structures. Cellulose 20:1765–1775

    CAS  Article  Google Scholar 

  • Anonymous (1995) Simulated gastric fluid and simulated intestinal fluid, TS. In the United States Pharmacopeia 23. The National Formulary 18; The United States Pharmacopeial Convention, Inc.: Rockville, MD

  • Beck S, Bouchard J, Berry R (2012) Dispersibility in water of dried nanocrystalline cellulose. Biomacromolecules 13:1486–1494

    CAS  Article  Google Scholar 

  • Bezerra MA, Santelli RE, Oliveira EP, Villar LS, Escaleira LA (2008) Response surface methodology (RSM) as a tool for optimization in analytical chemistry. Talanta 76:965–977

    CAS  Article  Google Scholar 

  • Bruno FA, Shah NP (2003) Viability of two freeze-dried strains of Bifidobacterium and of commercial preparations at various temperatures during prolonged storage. J Food Sci 68:2336–2339

    CAS  Article  Google Scholar 

  • Caglar E, Kavaloglu SC, Kuscu OO, Sandalli N, Holgerson PL, Twetman S (2007) Effect of chewing gums containing xylitol or probiotic bacteria on salivary mutans streptococci and lactobacilli. Clin Oral Invest 11:425–429

    CAS  Article  Google Scholar 

  • Calinescu C, Mateescu AM (2008) Carboxymethyl high amylose starch: chitosan self-stabilized matrix for probiotic colon delivery. Eur J Pharm Biopharm 70:582–589

    CAS  Article  Google Scholar 

  • Chan ES, Zhang Z (2002) Encapsulation of probiotic bacteria Lactobacillus acidophilus by direct compression. Trans IChemE 80 (part C), pp 78–82

  • Chan ES, Zhang Z (2005) Bioencapsulation by compression coating of probiotic bacteria for their protection in an acidic medium. Process Biochem 40:3346–3351

    CAS  Article  Google Scholar 

  • Chavarri M, Maranon I, Ares R, Ibanez CF, Marzo F, Villaran CM (2010) Microencapsulation of a probiotic and prebiotic in alginate-chitosan capsules improves survival in simulated gastro-intestinal conditions. Int J Food Microbiol 142:185–189

    CAS  Article  Google Scholar 

  • Cook TC, Tzortzis G, Charalampopoulos D, Khutoryanskiy VV (2011) Production and evaluation of dry alginate-chitosan microcapsules as an enteric delivery vehicle for probiotic bacteria. Biomacromolecules 12:2834–2840

    CAS  Article  Google Scholar 

  • Cook TC, Tzortzis G, Charalampopoulos D, Khutoryanskiy VV (2012) Microencapsulation of probiotics for gastrointestinal delivery. J Control Release 162:56–67

    CAS  Article  Google Scholar 

  • Dong XM, Revol JF, Gray DG (1998) Effect of microcrystalline preparation conditions on the formation of colloid crystals of cellulose. Cellulose 5:19–32

    CAS  Article  Google Scholar 

  • FAO/WHO Experts’ Report (2001). Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. Cordoba, Argentina. ISSN 0254-4725

  • Gardiner GE, O’sullivan E, Kelly J, Auty MAE, Fitzgerald GF, Collins JK, Ross RP, Stanton C (2000) Comparative survival rates of human-derived probiotic Lactobacillus paracasei and L. salivarius strains during heat treatment and spray drying. Appl Environ Microbiol 66:2605–2612

    CAS  Article  Google Scholar 

  • Habibi Y, Lucia LA, Rojas OJ (2010) Cellulose nanocrystals: chemistry, self-assembly, and applications. Chem Rev 110:3479–3500

    CAS  Article  Google Scholar 

  • Higl B, Kurtmann L, Carlsen CU, Ratjen J, Först P, Skibsted LH, Kulozik U, Risbo J (2007) Impact of water activity, temperature, and physical state on the storage stability of Lactobacillus paracasei ssp. freeze-dried in a lactose matrix. Biotechnol Prog 23:794–800

    CAS  Article  Google Scholar 

  • Hodsdon AC, Mitchell JR, Davies MC, Melia CD (1995) Structure and behaviour in hydrophilic matrix sustained release dosage forms. 3. The influence of pH on the sustained-release performance and internal gel structure of sodium alginate matrices. J Control Release 33:143–152

    CAS  Article  Google Scholar 

  • Howard JR, Timmins P (1988) Controlled release formulation. US Patent: 4,792,452

  • Huq T, Khan A, Khan AR, Riedl R, Lacroix M (2013) Encapsulation of probiotic bacteria in biopolymeric system. Crit Rev Food Sci Nutr 53:1–8

    Article  Google Scholar 

  • Iyer C, Kailasapathy K (2005) Effect of co-encapsulation of probiotics with prebiotics on increasing the viability of encapsulated bacteria under in vitro acidic and bile salt conditions and in yogurt. J Food Sci 70:18–23

    Google Scholar 

  • Khan A, Huq T, Saha M, Khan RA, Khan MA, Gafur MA (2010) Effect of silane treatment on the mechanical and interfacial properties of calcium alginate fiber reinforced polypropylene composite. J Compos Mater. doi:10.1177/0021998310371536

    Google Scholar 

  • Khan A, Vu KD, Chauve G, Bouchard J, Riedl B, Lacroix M (2014) Optimization of microfluidization for the homogeneous distribution of cellulose nanocrystals (CNCs) in biopolymeric matrix. Cellulose 21:3457–3468

    CAS  Article  Google Scholar 

  • Klayraung S, Viernstein H, Okonogi S (2009) Development of tablets containing probiotics: effects of formulation and processing parameters on bacterial viability. Int J Pharm 370:54–60

    CAS  Article  Google Scholar 

  • Kolakovic R, Peltonen L, Laaksonen T, Putkisto K, Laukkanen A, Hirvonen J (2011) Spray-dried cellulose nanofibers as novel tablet excipient. AAPS PharmSciTech 12:1366–1373

    CAS  Article  Google Scholar 

  • Kovacs T, Naish V, O’connor B, Blaise C, Gagne F, Hall L, Trudeau V, Martell P (2010) An ecotoxicological characterization of nanocrystalline cellulose (NCC). Nanotoxicology 4:255–270

    CAS  Article  Google Scholar 

  • Lavermicocca P (2006) Highlights on new food research. Dig Liver Dis 38:S295–S299

    Article  Google Scholar 

  • Le-Tien C, Millette M, Mateescu MA, Lacroix M (2004) Modified alginate and chitosan for lactic acid bacteria immobilization. Biotechnol Appl Biochem 39:347–354

    CAS  Article  Google Scholar 

  • Liew CV, Chan LW, Ching AL, Heng PWS (2006) Evaluation of sodium alginate as drug release modifier in matrix tablets. Int J Pharm 309:25–37

    CAS  Article  Google Scholar 

  • Liu L, Fishman ML, Kost J, Hicks KB (2003) Pectin-based systems for colon-specific drug delivery via oral route. Biomaterials 24:3333–3343

    CAS  Article  Google Scholar 

  • Maggi L, Mastromarino P, Macchia S, Brigidi P, Pirovano F, Matteuzzi D, Conte U (2000) Technological and biological evaluation of tablets containing different strains of lactobacilli for vaginal administration. Eur J Pharm Biopharm 50:389–395

    CAS  Article  Google Scholar 

  • Pelkman CL, Navia JL, Miller AE, Pohle RJ (2007) Novel calcium-gelled, alginate-pectin beverage reduced energy intake in nondieting overweight and obese women: interactions with dietary restraint status. Am J Clin Nutr 86:1595–1602

    CAS  Google Scholar 

  • Picot A, Lacroix C (2004) Encapsulation of bifidobacteria in whey protein-based microcapsules and survival in simulated gastrointestinal conditions and in yoghurt. Int Dairy J 14:505–515

    CAS  Article  Google Scholar 

  • Porubcan SR (2006) Formulations to increase in vivo survival of probiotic bacteria and extend their shelf life. US Patent: US 7122370B2

  • Poulin JF, Caillard R, Subirade M (2011) β-Lactoglobulin tablets as a suitable vehicle for protection and intestinal delivery of probiotic bacteria. Int J Pharm 405:47–54

    CAS  Article  Google Scholar 

  • Revol JF, Bradford H, Giasson J, Marchessault RH, Gray DG (1992) Helicoidal self-ordering of cellulose microfibrils in aqueous suspension. Int J Biol Macromol 14:170–172

    CAS  Article  Google Scholar 

  • Sahadeva RPK, Leong SF, Chua KH, Tan CH, Chan HY, Tong EV, Wong SYW, Chan HK (2011) Survival of commercial probiotic strains to pH and bile. Int Food Res J 18:1515–1522

    Google Scholar 

  • Saxelin M, Tynkkynen S, Mattila-Sandholm T, de Vos WM (2005) Probiotic and other functional microbes: from markets to mechanisms. Curr Opin Biotech 16:204–211

    CAS  Article  Google Scholar 

  • Sperger DM, Fu S, Block LH, Munson EJ (2011) Analysis of composition, molecular weight, and water content variations in sodium alginate using solid-state NMR spectroscopy. J Pharm Sci 100:8

    Article  Google Scholar 

  • Sriamornsak P, Thirawong N, Korkerd K (2007a) Swelling, erosion and release behavior of alginate-based matrix tablets. Eur J Pharm Biopharm 66:435–450

    CAS  Article  Google Scholar 

  • Sriamornsak S, Thirawong N, Weerapol Y, Nunthanid J, Sungthongjeen S (2007b) Swelling and erosion of pectin matrix tablets and their impact on drug release behavior. Eur J Pharm Biopharm 67:211–219

    CAS  Article  Google Scholar 

  • Stadler M, Viernstein H (2003) Optimization of formulation containing viable lactic acid bacteria. Int J Pharm 256:117–122

    CAS  Article  Google Scholar 

  • Thakur BR, Singh RK, Handa AK, Rao MA (1997) Chemistry and uses of pectin: a review. Crit Rev Food Sci Nutr 37:1

    Article  Google Scholar 

  • Timmins P, Delargy AM, Howard JR (1997) Optimization and characterization of a pH-independent extended-release hydrophilic matrix tablet. Pharm Dev Tech 2:25–31

    CAS  Article  Google Scholar 

  • Toft K, Grasdalen H, Smidsrod O (1986) Synergistic gelation of alginates and pectins. In: Fishman ML, Jen JJ (eds) Chemistry and function of pectins, vol 310. American Chemical Society. ACS Series, Washington, pp 117–133

    Chapter  Google Scholar 

  • Vasiljevic T, Shah NP (2008) Probiotics—from Metchnikoff to bioactives. Int Dairy J 18:714–728

    CAS  Article  Google Scholar 

Download references

Acknowledgments

This research was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) and by FPInnovations (Pointe-Claire, Québec, Canada) through the RDC program. Tanzina Huq is the recipient of a scholarship from Universitaire Fondation Armand-Frappier.

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Correspondence to Monique Lacroix.

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Huq, T., Vu, K.D., Riedl, B. et al. Development of probiotic tablet using alginate, pectin, and cellulose nanocrystals as excipients. Cellulose 23, 1967–1978 (2016). https://doi.org/10.1007/s10570-016-0905-2

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  • DOI: https://doi.org/10.1007/s10570-016-0905-2

Keywords

  • Cellulose nanocrystals
  • Pectin
  • Alginate
  • Probiotic tablet
  • Central composite design