Skip to main content
Log in

Comparison between solid and liquid acids for production of low molecular weight chitosan using systematic DOE-based approach

  • Original Paper
  • Published:
Cellulose Aims and scope Submit manuscript

Abstract

Chitosan is an abundantly available biodegradable polymer with diverse applications in various chemical and biomedical industries. However, it has remained underutilized due to its bulky and intractable nature, limiting its application in various fields. The major drawback, however, is poor aqueous solubility and thus preparation of low molecular weight derivatives of chitosan (LMWC) is an ideal solution to overcome the drawbacks associated with the parent polymer. The present study reports a sustainable method to produce LMWC, using H-β Zeolite as a green catalyst in comparison to the traditional depolymerization methods, based on nitrous acid. Successful decrease in molecular weight from 1157 to 175 kDa was achieved as studied by gel permeation chromatography. Furthermore, spray drying assisted in achieving uniform sized particles of LMWC of size less than 100 µm. Integration of response surface methodology for process optimization led to the negligible formation of by-products like 5-hydroxymethylfurfural. Comparative investigations confirmed the consistency of the developed method, simultaneously presenting additional advantages such as catalyst reusability, process reproducibility and process safety. Our findings demonstrate a greener approach for preparation of consistent quality LMWC, by implementing systemic stratagem of design of experiments.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Allan GG, Peyron M (1995) Molecular weight manipulation of chitosan II: prediction and control of extent of depolymerization by nitrous acid. Carbohydr Res 277:273–282

    Article  CAS  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

    Article  CAS  PubMed  Google Scholar 

  • Camblor M, Corma A, Valencia S (1998) Characterization of nanocrystalline zeolite Beta. Microporous Mesoporous Mater 25:59–74

    Article  CAS  Google Scholar 

  • Chopra S, Patil GV, Motwani SK (2007) Release modulating hydrophilic matrix systems of losartan potassium: optimization of formulation using statistical experimental design. Eur J Pharm Biopharm 66:73–82

    Article  CAS  PubMed  Google Scholar 

  • Dimitrijevic R, Lutz W, Ritzmann A (2006) Hydrothermal stability of zeolites: determination of extra-framework species of HY faujasite-type steamed zeolite. J Phys Chem Solids 67:1741–1748

    Article  CAS  Google Scholar 

  • Ding L, Zheng Y, Hong Y, Ring Z (2007) Effect of particle size on the hydrothermal stability of zeolite beta. Microporous Mesoporous Mater 101:432–439

    Article  CAS  Google Scholar 

  • Domard A, Rinaudo M (1983) Preparation and characterization of fully deacetylated chitosan. Int J Biol Macromol 5:49–52

    Article  CAS  Google Scholar 

  • Focher B, Naggi A, Torri G, Cosani A, Terbojevich M (1992) Chitosans from Euphausia superba. 2: characterization of solid state structure. Carbohydr Polym 18:43–49

    Article  CAS  Google Scholar 

  • Frey DD, Engelhardt F, Greitzer EM (2003) A role for “one-factor-at-a-time” experimentation in parameter design. Res Eng Des 14:65–74

    Article  Google Scholar 

  • Guinesi LS, Cavalheiro ETG (2006) The use of DSC curves to determine the acetylation degree of chitin/chitosan samples. Thermochim Acta 444:128–133

    Article  CAS  Google Scholar 

  • Guisnet M, Magnoux P (1997) Deactivation by coking of zeolite catalysts. Prevention of deactivation. Optimal conditions for regeneration. Catal Today 36:477–483

    Article  CAS  Google Scholar 

  • He P, Davis SS, Illum L (1999) Chitosan microspheres prepared by spray drying. Int J Pharm 187:53–65

    Article  CAS  PubMed  Google Scholar 

  • Huang Y-B, Fu Y (2013) Hydrolysis of cellulose to glucose by solid acid catalysts. Green Chem 15:1095–1111

    Article  CAS  Google Scholar 

  • Kas HS (1997) Chitosan: properties, preparations and application to microparticulate systems. J Microencapsul 14:689–711

    Article  CAS  PubMed  Google Scholar 

  • Kim S-K (2010) Chitin, chitosan, oligosaccharides and their derivatives: biological activities and applications. CRC Press, Boca Raton

    Book  Google Scholar 

  • Kim S-K, Rajapakse N (2005) Enzymatic production and biological activities of chitosan oligosaccharides (COS): a review. Carbohydr Polym 62:357–368

    Article  CAS  Google Scholar 

  • Kittur F, Prashanth KH, Sankar KU, Tharanathan R (2002) Characterization of chitin, chitosan and their carboxymethyl derivatives by differential scanning calorimetry. Carbohydr Polym 49:185–193

    Article  CAS  Google Scholar 

  • Krishnan RA et al (2016) Proton play in the formation of low molecular weight chitosan (LWCS) by hydrolyzing chitosan with a carbon based solid acid. Carbohydr Polym 151:417–425

    Article  CAS  PubMed  Google Scholar 

  • Kumar MNR (2000) A review of chitin and chitosan applications. React Funct Polym 46:1–27

    Article  CAS  Google Scholar 

  • Kumar MR, Muzzarelli RA, Muzzarelli C, Sashiwa H, Domb A (2004) Chitosan chemistry and pharmaceutical perspectives. Chem Rev 104:6017–6084

    Article  PubMed  Google Scholar 

  • Kumar ABV, Varadaraj MC, Gowda LR, Tharanathan RN (2007) Low molecular weight chitosans—preparation with the aid of pronase, characterization and their bactericidal activity towards Bacillus cereus and Escherichia coli. Biochim Biophys Acta (BBA) Gen Subj 1770:495–505

    Article  CAS  Google Scholar 

  • Kumirska J, Czerwicka M, Kaczyński Z, Bychowska A, Brzozowski K, Thöming J, Stepnowski P (2010) Application of spectroscopic methods for structural analysis of chitin and chitosan. Mar Drugs 8:1567–1636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee S-B, Jeong G-T (2015) Catalytic conversion of chitosan to 5-hydroxymethylfurfural under low temperature hydrothermal process. Appl Biochem Biotechnol 176:1151–1161

    Article  CAS  PubMed  Google Scholar 

  • Li J, Du Y, Yang J, Feng T, Li A, Chen P (2005) Preparation and characterisation of low molecular weight chitosan and chito-oligomers by a commercial enzyme. Polym Degrad Stab 87:441–448

    Article  CAS  Google Scholar 

  • Liu S-b, Wu J-F, Ma L-J, Tsai T-C, Wang I (1991) On the thermal stability of zeolite beta. J Catal 132:432–439

    Article  CAS  Google Scholar 

  • Liu L, Wang X, Zou H, Yu M, Xie W (2017) Optimizing synthesis parameters of short carbon fiber reinforced polysulfonamide composites by using response surface methodology. Polym Test 59:355–361

    Article  CAS  Google Scholar 

  • Mao S, Shuai X, Unger F, Simon M, Bi D, Kissel T (2004) The depolymerization of chitosan: effects on physicochemical and biological properties. Int J Pharm 281:45–54

    Article  CAS  PubMed  Google Scholar 

  • Motwani SK, Chopra S, Talegaonkar S, Kohli K, Ahmad FJ, Khar RK (2008) Chitosan–sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: formulation, optimisation and in vitro characterisation. Eur J Pharm Biopharm 68:513–525

    CAS  PubMed  Google Scholar 

  • Moura FA, Macagnan FT, Silva LP (2015) Oligosaccharide production by hydrolysis of polysaccharides: a review. Int J Food Sci Technol 50:275–281

    Article  CAS  Google Scholar 

  • Nikolla E, Román-Leshkov Y, Moliner M, Davis ME (2011) “One-pot” synthesis of 5-(hydroxymethyl) furfural from carbohydrates using tin-beta zeolite. Acs Catal 1:408–410

    Article  CAS  Google Scholar 

  • Nobandegani MS, Birjandi MRS, Darbandi T, Khalilipour MM, Shahraki F, Mohebbi-Kalhori D (2016) An industrial Steam Methane Reformer optimization using response surface methodology. J Nat Gas Sci Eng 36:540–549

    Article  CAS  Google Scholar 

  • Onda A, Ochi T, Yanagisawa K (2008) Selective hydrolysis of cellulose into glucose over solid acid catalysts. Green Chem 10:1033–1037

    Article  CAS  Google Scholar 

  • Paudel A, Worku ZA, Meeus J, Guns S, Van den Mooter G (2013) Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: formulation and process considerations. Int J Pharm 453:253–284

    Article  CAS  PubMed  Google Scholar 

  • Paulo F, Santos L (2017) Design of experiments for microencapsulation applications: a review. Mater Sci Eng C 77:1327–1340

    Article  CAS  Google Scholar 

  • Prashanth KH, Tharanathan R (2005) Depolymerized products of chitosan as potent inhibitors of tumor-induced angiogenesis. Biochim Biophys Acta (BBA) Gen Subj 1722:22–29

    Article  CAS  Google Scholar 

  • Rabea EI, Badawy ME-T, Stevens CV, Smagghe G, Steurbaut W (2003) Chitosan as antimicrobial agent: applications and mode of action. Biomacromolecules 4:1457–1465

    Article  CAS  PubMed  Google Scholar 

  • Rinaldi R, Palkovits R, Schüth F (2008) Depolymerization of cellulose using solid catalysts in ionic liquids. Angew Chem Int Ed 47:8047–8050

    Article  CAS  Google Scholar 

  • Rosatella AA, Simeonov SP, Frade RF, Afonso CA (2011) 5-Hydroxymethylfurfural (HMF) as a building block platform: biological properties, synthesis and synthetic applications. Green Chem 13:754–793

    Article  CAS  Google Scholar 

  • Sabnis S, Block LH (1997) Improved infrared spectroscopic method for the analysis of degree of N-deacetylation of chitosan. Polym Bull 39:67–71

    Article  CAS  Google Scholar 

  • Tsai G-J, Tsai M-T, Lee J-M, Zhong M-Z (2006) Effects of chitosan and a low-molecular-weight chitosan on Bacillus cereus and application in the preservation of cooked rice. J Food Prot 69:2168–2175

    Article  CAS  PubMed  Google Scholar 

  • van Strien RT, Gent JF, Belanger K, Triche E, Bracken MB, Leaderer BP (2004) Exposure to NO2 and nitrous acid and respiratory symptoms in the first year of life. Epidemiology 15:471–478

    Article  PubMed  Google Scholar 

  • Vasilieva T et al (2017) Formation of low molecular weight oligomers from chitin and chitosan stimulated by plasma-assisted processes. Carbohydr Polym 163:54–61

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Xu W, Ren J, Liu X, Lu G, Wang Y (2011) Efficient catalytic conversion of fructose into hydroxymethylfurfural by a novel carbon-based solid acid. Green Chem 13:2678–2681

    Article  CAS  Google Scholar 

  • Ward JW (1970) The nature of active sites on zeolites. J Catal 17:355–358. https://doi.org/10.1016/0021-9517(70)90111-9

    Article  CAS  Google Scholar 

  • Weitkamp J (2000) Zeolites and catalysis. Solid State Ion 131:175–188

    Article  CAS  Google Scholar 

  • Xu B, Sievers C, Hong SB, Prins R, van Bokhoven JA (2006) Catalytic activity of Brønsted acid sites in zeolites: intrinsic activity, rate-limiting step, and influence of the local structure of the acid sites. J Catal 244:163–168

    Article  CAS  Google Scholar 

  • Zheng B, Wen Z-S, Huang Y-J, Xia M-S, Xiang X-W, Qu Y-L (2016) Molecular weight-dependent immunostimulative activity of low molecular weight chitosan via regulating NF-κB and AP-1 signaling pathways in RAW264. 7 macrophages. Mar Drugs 14:169

    Article  CAS  PubMed Central  Google Scholar 

  • Zhou L, Liu Z, Bai Y, Lu T, Yang X, Xu J (2016) Hydrolysis of cellobiose catalyzed by zeolites—the role of acidity and micropore structure. J Energy Chem 25:141–145

    Article  Google Scholar 

Download references

Acknowledgments

The authors are thankful to University Grants Commission for the UGC-SAP fellowship [F.25-1/2014-15 (BSR)/No. F.8-10/2007(BSR)] and [F.4-1/2006 (BSR)/8-10/2007(BSR)] for financial support. The authors would like to acknowledge DST-Nanomission (Sanction No. SR/NM/NS-1145/2012) for the zetasizer instrument and DST-FIST (Sanction No. SR/FST/ETII-058/2013 (C)) for Gel Permeation Chromatography. The authors are also very thankful to Nano-xpert technologies for technical support and providing gift sample of solid acid. Special thanks to Tejal Pant and Manish Gore for assistance in drafting the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Prajakta Dandekar or Ratnesh Jain.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 922 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Patil, S., Krishnan, R.A., Bhangde, S. et al. Comparison between solid and liquid acids for production of low molecular weight chitosan using systematic DOE-based approach. Cellulose 25, 5643–5658 (2018). https://doi.org/10.1007/s10570-018-1986-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10570-018-1986-x

Keywords

Navigation