Influence of spray-drying process on properties of chitosan/xanthan gum polyelectrolyte complexes as carriers for oral delivery of ibuprofen

  • Ana Ćirić Faculty of Pharmacy - University of Belgrade, Department of Pharmaceutical Technology and Cosmetology
  • Jelena Milinković Budinčić University of Novi Sad - Faculty of Technology, Department of Biotechnology and Pharmaceutical Engineering
  • Đorđe Medarević University of Belgrade - Faculty of Pharmacy, Department of Pharmaceutical Technology and Cosmetology
  • Vladimir Dobričić University of Belgrade - Faculty of Pharmacy, Department of Pharmaceutical Chemistry
  • Milena Rmandić University of Belgrade - Faculty of Pharmacy, Department of Drug Analysis
  • Tanja Barudžija University of Belgrade - Vinča Institute of Nuclear Sciences, Laboratory for Theoretical Physics and Condensed Matter Physics
  • Anđelija Malenović University of Belgrade - Faculty of Pharmacy, Department of Drug Analysis
  • Lidija Petrović University of Novi Sad - Faculty of Technology, Department of Biotechnology and Pharmaceutical Engineering
  • Ljiljana Đekić University of Belgrade - Faculty of Pharmacy, Department of Pharmaceutical Technology and Cosmetology
Keywords: chitosan, xanthan gum, ibuprofen, spray-drying, controlled drug release

Abstract


Polyelectrolyte complexes (PECs) are attractive carriers with recognized potential to enhance oral delivery of poorly soluble high-dosed low-molecular-weight drugs. The formulation of solid oral dosage forms requires the drying of PECs, which may affect their physicochemical and biopharmaceutical properties. The aim of this study was to investigate the effect of spray-drying on the properties of ibuprofen-loaded chitosan/xanthan gum PECs and to assess the drug release kinetics from such PECs filled into hard capsules in comparison with corresponding PECs which are dried under ambient conditions. The yield, ibuprofen content, entrapment efficiency, and residual moisture content of spray-dried PECs were lower than those of ambient-dried PECs. Better flowability of spray-dried PECs was attributed to the almost spherical particle shape, shown by scanning electron microscopy. DSC and PXRD analysis confirmed the amorphization of ibuprofen during spray-drying. All the investigated PECs, obtained by drying under ambient conditions as well as by spray-drying, had high rehydration capacity both in 0.1 M hydrochloric acid (pH 1.2) and phosphate buffer pH 7.4. In vitro ibuprofen release from dried PECs was controlled during 12 h with the release of approximately 30% of entrapped ibuprofen. Spray-dried PECs provided better control of ibuprofen diffusion from the carrier compared to the ambient-dried ones.

References

Savjani KT, Gajjar AK, Savjani JK. Drug Solubility: Importance and Enhancement Techniques. ISRN Pharm. 2012;2012:1–10.

Meka VS, Sing MKG, Pichika MR, Nali SR, Kolapalli VRM, Kesharwani P. A comprehensive review on polyelectrolyte complexes. Drug Discov Today. 2017;22(11):1697–706.

Berger J, Reist M, Mayer JM, Felt O, Gurny R. Structure and interactions in chitosan hydrogels formed by complexation or aggregation for biomedical applications. Eur J Pharm Biopharm. 2004;57(1):35–52.

Berger J, Reist M, Mayer JM, Felt O, Peppas NA, Gurny R. Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications. Eur J Pharm Biopharm. 2004;57(1):19–34.

Ćirić A, Krajišnik D, Čalija B, Đekić L. Biocompatible non-covalent complexes of chitosan and different polymers: Characteristics and application in drug delivery. Arh Farm (Belgr). 2020;70(4):173–97.

Bigucci F, Luppi B, Cerchiara T, Sorrenti M, Bettinetti G, Rodriguez L, et al. Chitosan/pectin polyelectrolyte complexes: Selection of suitable preparative conditions for colon-specific delivery of vancomycin. Eur J Pharm Sci. 2008;35(5):435–41.

Bhattarai N, Gunn J, Zhang M. Chitosan-based hydrogels for controlled, localized drug delivery. Adv Drug Deliv Rev. 2010;62(1):83–99.

Naidu VGM, Madhusudhana K, Sashidhar RB, Ramakrishna S, Khar RK, Ahmed FJ, et al. Polyelectrolyte complexes of gum kondagogu and chitosan, as diclofenac carriers. Carbohydr Polym. 2009;76(3):464–71.

Maurstad G, Kitamura S, Stokke BT. Isothermal titration calorimetry study of the polyelectrolyte complexation of xanthan and chitosan samples of different degree of polymerization. Biopolymers. 2012;97(1):1–10.

Ćirić A, Medarević, Čalija B, Dobričić V, Mitrić M, Djekic L, et al. Study of chitosan/xanthan gum polyelectrolyte complexes formation, solid state and influence on ibuprofen release kinetics. Int J Biol Macromol. 2020;148:942–55.

Toniazzo T, Berbel IF, Cho S, Fávaro-Trindade CS, Moraes ICF, Pinho SC. β-carotene-loaded liposome dispersions stabilized with xanthan and guar gums: Physico-chemical stability and feasibility of application in yogurt. LWT - Food Sci Technol. 2014;59(2P2):1265–73.

Petri DFS. Xanthan gum: A versatile biopolymer for biomedical and technological applications. J Appl Polym Sci. 2015;132(23):42035.

Moin A, Shivakumar H, Deb T, Ramireddy B. In vitro-in vivo evaluation of xanthan gum and eudragit inter polyelectrolyte complex based sustained release tablets. Int J Pharm Investig. 2015;5(1):65–72.

Argin-Soysal S, Kofinas P, Lo YM. Effect of complexation conditions on xanthan-chitosan polyelectrolyte complex gels. Food Hydrocoll. 2009;23:202–9.

Ćirić A, Medarević Đ, Čalija B, Dobričić V, Rmandić M, Barudžija T, et al. Effect of ibuprofen entrapment procedure on physicochemical and controlled drug release performances of chitosan/xanthan gum polyelectrolyte complexes. Int J Biol Macromol. 2021;167:547–58.

Hamman JH. Chitosan based polyelectrolyte complexes as potential carrier materials in drug delivery systems. Mar Drugs. 2010;8(4):1305–22.

Bourganis V, Karamanidou T, Kammona O, Kiparissides C. Polyelectrolyte complexes as prospective carriers for the oral delivery of protein therapeutics. Eur J Pharm Biopharm. 2017;111:44–60.

Cerchiara T, Abruzzo A, Parolin C, Vitali B, Bigucci F, Gallucci MC, et al. Microparticles based on chitosan/carboxymethylcellulose polyelectrolyte complexes for colon delivery of vancomycin. Carbohydr Polym. 2016;143:124–30.

Bigucci F, Abruzzo A, Vitali B, Saladini B, Cerchiara T, Gallucci MC, et al. Vaginal inserts based on chitosan and carboxymethylcellulose complexes for local delivery of chlorhexidine: Preparation, characterization and antimicrobial activity. Int J Pharm. 2015;478(2):456–63.

Čalija B, Savic S, Krajišnik D, Daniels R, Vučen S, Markovic B, et al. PH-sensitive polyelectrolyte films derived from submicron chitosan/Eudragit® L 100-55 complexes: Physicochemical characterization and in vitro drug release. J Appl Polym Sci. 2015;132(39):1–9.

Hu Q, Wang T, Zhou M, Xue J, Luo Y. Formation of redispersible polyelectrolyte complex nanoparticles from gallic acid-chitosan conjugate and gum arabic. Int J Biol Macromol. 2016;92:812–9.

Dimer FA, Ortiz M, Pohlmann AR, Guterres SS. Inhalable resveratrol microparticles produced by vibrational atomization spray drying for treating pulmonary arterial hypertension. J Drug Deliv Sci Technol. 2015;29:152–8.

Mishra B, Mishra M, Yadav SK. Antibacterial loaded spray dried chitosan polyelectrolyte complexes as dry powder aerosol for the treatment of lung infections. Iran J Pharm Res. 2017;16(1):74–92.

Irvine J, Afrose A, Islam N. Formulation and delivery strategies of ibuprofen: challenges and opportunities. Drug Dev Ind Pharm. 2018;44(2):173–83.

Wong TW, Chan LW, Kho S Bin, Sia Heng PW. Design of controlled-release solid dosage forms of alginate and chitosan using microwave. J Control Release. 2002;84(3):99–114.

Das S, Ng KY, Ho PC. Formulation and optimization of zinc-pectinate beads for the controlled delivery of resveratrol. AAPS PharmSciTech. 2010;11(2):729–42.

Das S, Ng KY. Colon-specific delivery of resveratrol: Optimization of multi-particulate calcium-pectinate carrier. Int J Pharm. 2010;385(1–2):20–8.

Das S, Chaudhury A, Ng KY. Preparation and evaluation of zinc-pectin-chitosan composite particles for drug delivery to the colon: Role of chitosan in modifying in vitro and in vivo drug release. Int J Pharm. 2011;406(1–2):11–20.

Patel B, Patel J, Chakraborty S. Review of Patents and Application of Spray Drying in Pharmaceutical, Food and Flavor Industry. Recent Pat Drug Deliv Formul. 2014;8(1):63–78.

Pontip B, Suchada P, Sriamornsak P. Effect of formulations and spray drying process conditions on physical properties of resveratrol spray-dried emulsions. Key Eng Mater. 2019;819:246–51.

Caddeo C, Nácher A, Díez-Sales O, Merino-Sanjuán M, Fadda AM, Manconi M. Chitosan-xanthan gum microparticle-based oral tablet for colon-targeted and sustained delivery of quercetin. J Microencapsul. 2014;31(7):694–9.

Potthast H, Dressman JB, Junginger HE, Midha KK, Oeser H, Shah VP, et al. Biowaiver monographs for immediate release solid oral dosage forms: Ibuprofen. J Pharm Sci. 2005;94(10):2121–31.

Elkordya AA, Essa EA. Effects of spray drying and spray chilling on ibuprofen dissolution. Iran J Pharm Sci. 2010;6(1):3–12.

Sogias IA, Williams AC, Khutoryanskiy V V. Chitosan-based mucoadhesive tablets for oral delivery of ibuprofen. Int J Pharm. 2012;436(1–2):602–10.

Laracuente ML, Yu MH, McHugh KJ. Zero-order drug delivery: State of the art and future prospects. J Control Release. 2020;327:834–56.

Salome AC, Godswill CO, Ikechukwu IO. Kinetics and mechanisms of drug release from swellable and non swellable matrices: A review. Res J Pharm Biol Chem Sci. 2013;4(2):97–103.

Siepmann J, Peppas NA. Higuchi equation: Derivation, applications, use and misuse. Int J Pharm. 2011;418(1):6–12.

Wu IY, Bala S, Škalko-Basnet N, di Cagno MP. Interpreting non-linear drug diffusion data: Utilizing Korsmeyer-Peppas model to study drug release from liposomes. Eur J Pharm Sci. 2019;138:105026.

Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, et al. DDSolver: An add-in program for modeling and comparison of drug dissolution profiles. AAPS J. 2010;12(3):263–71.

Diaz DA, Colgan ST, Langer CS, Bandi NT, Likar MD, Van Alstine L. Dissolution Similarity Requirements: How Similar or Dissimilar Are the Global Regulatory Expectations? AAPS J. 2016;18(1):15–22.

Ceschan NE, Bucalá V, Mateos MV, Smyth HDC, Ramírez-Rigo MV. Carrier free indomethacin microparticles for dry powder inhalation. Int J Pharm. 2018;549(1–2):169–78.

Dima C, Pətraşcu L, Cantaragiu A, Alexe P, Dima Ş. The kinetics of the swelling process and the release mechanisms of Coriandrum sativum L. essential oil from chitosan/alginate/inulin microcapsules. Food Chem. 2016;195:39–48.

Mladenovska K, Raicki RS, Janevik EI, Ristoski T, Pavlova MJ, Kavrakovski Z, et al. Colon-specific delivery of 5-aminosalicylic acid from chitosan-Ca-alginate microparticles. Int J Pharm. 2007;342(1–2):124–36.

Ding B, Li C, Pan M, Chiou Y, Li Z, Wei S, et al. Microencapsulation of xanthan gum based on palm stearin/beeswax matrix as wall system. J Food Process Eng. 2019;42(5):e13102.

Budinčić JM, Petrović L, Đekić L, Fraj J, Bučko S, Katona J, et al. Study of vitamin E microencapsulation and controlled release from chitosan/sodium lauryl ether sulfate microcapsules. Carbohydr Polym. 2021;251:116988.

Lee BJ. Pharmaceutical preformulation: physicochemical properties of excipients and powders and tablet characterization. In: Gad SC, editor, Pharmaceutical Manufacturing Handbook: Production and Processes. Hoboken, New Jersey: John Wiley & Sons, Inc.; 2008; p. 905–9.

Chomto P, Nunthanid J. Physicochemical and powder characteristics of various citrus pectins and their application for oral pharmaceutical tablets. Carbohydr Polym. 2017;174:25–31.

Crouter A, Briens L. The effect of moisture on the flowability of pharmaceutical excipients. AAPS PharmSciTech. 2014;15(1):65–74.

Elizalde-Peña EA, Zarate-Triviño DG, Nuño-Donlucas SM, Medina-Torres L, Gough JE, Sanchez IC, et al. Synthesis and characterization of a hybrid (chitosan-g-glycidyl methacrylate)-xanthan hydrogel. J Biomater Sci Polym Ed. 2013;24(12):1426–42.

Thakur A, Monga S, Wanchoo RK. Sorption and drug release studies from semi-interpenetrating polymer networks of Chitosan and Xanthan Gum. Chem Biochem Eng Q. 2014;28(1):105–15.

Rowe RC, Sheskey PJ, Quinn ME, editors. Handbook of Pharmaceutical Excipients. 6th ed. London: Pharmaceutical Press; 2009. 783 p.

Hussain A, Smith G, Khan KA, Bukhari NI, Pedge NI, Ermolina I. Solubility and dissolution rate enhancement of ibuprofen by co-milling with polymeric excipients. Eur J Pharm Sci. 2018;123:395–403.

Abioye AO, Armitage R, Kola-Mustapha AT. Thermodynamic Changes Induced by Intermolecular Interaction between Ibuprofen and Chitosan: Effect on Crystal Habit, Solubility and in Vitro Release Kinetics of Ibuprofen. Pharm Res. 2016;33(2):337–57.

Wikarsa S, Durand D, Delarbre JL, Baylac G, Bataille B. The improvement of ibuprofen dissolution rate through microparticles spray drying processed in an aqueous system. Drug Dev Ind Pharm. 2008;34(5):485–91.

Lv X, Zhang W, Liu Y, Zhao Y, Zhang J, Hou M. Hygroscopicity modulation of hydrogels based on carboxymethyl chitosan/Alginate polyelectrolyte complexes and its application as pH-sensitive delivery system. Carbohydr Polym. 2018;198:86–93.

Nath SD, Abueva C, Kim B, Lee BT. Chitosan-hyaluronic acid polyelectrolyte complex scaffold crosslinked with genipin for immobilization and controlled release of BMP-2. Carbohydr Polym. 2015;115:160–9.

Chen Y, Yan X, Zhao J, Feng H, Li P, Tong Z, et al. Preparation of the chitosan/poly(glutamic acid)/alginate polyelectrolyte complexing hydrogel and study on its drug releasing property. Carbohydr Polym. 2018;191:8–16.

Shang Q, Huang S, Zhang A, Feng J, Yang S. The binary complex of poly(PEGMA-co-MAA) hydrogel and PLGA nanoparticles as a novel oral drug delivery system for ibuprofen delivery. J Biomater Sci Polym Ed. 2017;28(16):1874–87.

Ofokansi KC, Kenechukwu FC. Formulation Development and Evaluation of Drug Release Kinetics from Colon-Targeted Ibuprofen Tablets Based on Eudragit RL 100-Chitosan Interpolyelectrolyte Complexes. ISRN Pharm. 2013;2013:1–8.

Published
2022/02/19
Section
Original scientific paper