Generic placeholder image

Drug Delivery Letters


ISSN (Print): 2210-3031
ISSN (Online): 2210-304X

Research Article

Berberine Hydrochloride Embedded Chitosan-based Novel Floating Microspheres: Optimization, Characterization, and in vivo Anti-ulcer Potential

Author(s): Radha Rani, Manish Kumar*, Ravinder Verma, Pravin Gupta, Beena Kumari, Rakesh Pahwa, Vineet Mittal, Shailendra Bhatt and Deepak Kaushik

Volume 12, Issue 4, 2022

Published on: 01 September, 2022

Page: [287 - 301] Pages: 15

DOI: 10.2174/2210303112666220602123548

Price: $65


Background: Microspheres are controlled drug delivery systems (CDDS) due to their potential to encapsulate various drugs, nucleic acids, and proteins. Their benefits include greater biocompatibility, increased bioavailability, and controlled release. Presently, existing antiulcer agents suffer from severe side effects, which has restricted their utility and encouraged the requirement of a harmless and proficient new antiulcer agent. The rationale of the present research work was to improve the absorption of the drug in the stomach for better anti-ulcer action and fewer side effects.

Objective: This study aimed to prepare and examine floating microspheres using berberine hydrochloride to increase gastric retention without interacting with the mucosa inside the stomach.

Methods: The capillary extrusion technique was used with the aid of chitosan, a polymer, in addition to sodium lauryl sulphate, a crosslinking agent. Scanning electron microscopy characterized the surface morphology of the prepared microspheres. The effects of polymeric concentration as well as the concentration of cross-link agent on percent yield, in vitro floating behavior, and in vitro drug release were efficiently assessed.

Results: The drug follows a mechanism for prolonged release, known as diffusion. Prolonged drug release (12 hrs) was seen in the prepared microspheres, and they also remained buoyant for around 10 hrs. In vivo evaluation study was successfully performed. From the values of ulcer indexes for various groups, percentage protection was determined. The treatment group (F-2 formulation) showed maximum percentage protection of 97.29%.

Conclusion: The prepared floating microspheres can make potential candidates adaptable to any intra- gastric conditions for multiple-unit delivery devices.

Keywords: Chitosan, sodium lauryl sulphate, capillary extrusion method, floating microspheres, berberine hydrochloride, GIT.

Graphical Abstract
Awasthi, R.; Kulkarni, G.T. Development of novel gastroretentive drug delivery system of gliclazide: Hollow beads. Drug Dev. Ind. Pharm., 2014, 40(3), 398-408.
[] [PMID: 23418961]
Zhang, Y.; Zhang, X.T.; Zhang, Q.; Wang, B.; Zhang, T. Formulation development and evaluation of gastroretentive floating beads with Brucea javanica oil using ionotropic gelation technology. Chin. J. Nat. Med., 2018, 16(4), 293-301.
[] [PMID: 29703329]
Maietta, S.; Russo, T.; Santis, R.; Ronca, D.; Riccardi, F.; Catauro, M.; Martorelli, M.; Gloria, A. Further theoretical insight into the mechanical properties of polycaprolactone loaded with organic–inorganic hybrid fillers. Materials, 2018, 11(2), 312.
[] [PMID: 29466299]
O’Hagan, D.T.; Singh, M.; Ulmer, J.B. Microparticle-based technologies for vaccines. Methods, 2006, 40(1), 10-19.
[] [PMID: 16997709]
Lengyel, M.; Kállai-Szabó, N.; Antal, V.; Laki, A.J.; Antal, I. Microparticles, microspheres, and microcapsules for advanced drug delivery. Sci. Pharm., 2019, 87(3), 20.
Bale, S.; Khurana, A.; Reddy, A.S.S.; Singh, M.; Godugu, C. Overview on therapeutic applications of microparticle drug delivery overview on therapeutic applications of microparticulate drug delivery systems. Crit. Rev. Ther. Drug Carrier Syst., 2016, 33(4), 309-361.
[] [PMID: 27910739]
Wang, B.H.; Longquin Hu, T.J.S. Drug delivery to the lymphatic system. Drug Delivery Principles and Applications; Wang, B.; Longquin Hu, T.J.S., Eds.; John Wiley and Sons Inc.: Hoboken, NJ, USA, 2016.
Xiong, Z.; Huang, J.; Wu, Y.; Gong, X. Robust multifunctional fluorine-free superhydrophobic fabrics for high-efficiency oil-water separation with ultrahigh flux. Nanoscale, 2022, 14(15), 5840-5850. Advance online publication
[] [PMID: 35353111]
Singh, M.; Verma, Y.; Rana, S.V. Potential toxicity of nickel nano and microparticles on the reproductive system of female rats: A comparative time-dependent study. Toxicol. Ind. Health, 2022, 38(4), 234-247.
[] [PMID: 35352587]
Iyer, G.; Dyawanapelly, S.; Jain, R.; Dandekar, P. An overview of Oral Insulin Delivery Strategies (OIDS). Int. J. Biol. Macromol, 2022, S0141-8130(22), 00614-6.
Nguyen, N.K.; Singha, P.; Dai, Y.; Rajan Sreejith, K.; Tran, D.T.; Phan, H.P.; Nguyen, N.T.; Ooi, C.H. Controllable high-performance liquid marble micromixer. Lab Chip, 2022, 22(8), 1508-1518.
[] [PMID: 35344578]
Monje, D.S.; Ruiz, O.S.; Valencia, G.C.; Mercado, D.F. Iron oxide nanoparticles embedded in organic microparticles from Yerba Mate useful for remediation of textile wastewater through a photo-Fenton treatment: Ilex paraguariensis as a platform of environmental interest - Part 1. Environ. Sci. Pollut. Res. Int., 2022.
[] [PMID: 35344143]
Freitas, S.; Merkle, H.P.; Gander, B. Microencapsulation by solvent extraction/evaporation: Reviewing the state of the art of microsphere preparation process technology. J. Control. Release, 2005, 102(2), 313-332.
[] [PMID: 15653154]
Mukund, J.Y.; Kantilal, B.R.; Sudhakar, R.N. Floating microspheres: A review. Braz. J. Pharm. Sci., 2012, 48(1), 17-30.
Berenguer, B.; Alarcón de la Lastra, C.; Moreno, F.J.; Martín, M.J. Chronic gastric ulcer healing in rats subjected to selective and non-selective cyclooxygenase-2 inhibitors. Eur. J. Pharmacol., 2002, 442(1-2), 125-135.
[] [PMID: 12020690]
Chouhan, M.; Chundawat, A.V.S.; Chauhan, C.S. Development and characterization of floating microspheres of esomeprazole magnesium trihydrate by solvent evaporation method. Int. J. Pharm. Sci. Res., 2017, 8(2), 686-697.
Fang, Z.; Jiang, R.; Zhang, L.; Wu, Y.; Zhao, X.; Zhao, L.; Li, J.; Zou, S.; Zhang, M.; Du, F. In situ fabrication of radiopaque microcapsules for oral delivery and real-time gastrointestinal tracking of Bifidobacterium. Int. J. Nanomedicine, 2018, 13, 4093-4105.
[] [PMID: 30034235]
Freiberg, S.; Zhu, X.X. Polymer microspheres for controlled drug release. Int. J. Pharm., 2004, 282(1-2), 1-18.
[] [PMID: 15336378]
Ghaffarian, R.; Herrero, E.P.; Oh, H.; Raghavan, S.R.; Muro, S. Chitosan-alginate microcapsules provide gastric protection and intestinal release of ICAM-1-targeting nanocarriers, enabling GI targeting in vivo. Adv. Funct. Mater., 2016, 26(20), 3382-3393.
[] [PMID: 27375374]
Gupta, P.; Kumar, M.; Kaushik, D. Pantoprazole sodium loaded microballoons for the systemic approach: In vitro and in vivo evaluation. Adv. Pharm. Bull., 2017, 7(3), 461-467.
[] [PMID: 29071229]
Haffor, A.S. Effect of myrrh (Commiphora molmol) on leukocyte levels before and during healing from gastric ulcer or skin injury. J. Immunotoxicol., 2010, 7(1), 68-75.
[] [PMID: 19995243]
Xu, J.; Strandman, S.; Zhu, J.X.; Barralet, J.; Cerruti, M. Genipin-crosslinked catechol-chitosan mucoadhesive hydrogels for buccal drug delivery. Biomaterials, 2015, 37, 395-404.
[] [PMID: 25453967]
Khan, R.; Arora, R.; Ojha, A.; Chopra, H.; Kumud, U. Formulation and evaluation of floating microspheres of levofloxacin. Int. Res. J. Pharm, 2018, 9(7), 186-191.
Kobayashi, T.; Ohta, Y.; Yoshino, J.; Nakazawa, S. Teprenone promotes the healing of acetic acid-induced chronic gastric ulcers in rats by inhibiting neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues. Pharmacol. Res., 2001, 43(1), 23-30.
[] [PMID: 11207062]
Kumari, B. Recent development in floating drug delivery system: A review. Asian J. Pharm. Pharmacol., 2018, 4(2), 131-139.
Verma, R.; Kaushik, D. Design and optimization of candesartan loaded self-nanoemulsifying drug delivery system for improving its dissolution rate and pharmacodynamic potential. Drug Deliv., 2020, 27(1), 756-771.
[] [PMID: 32397771]
Sankar, R.; Jain, S.K. Development and characterization of gastroretentive sustained-release formulation by combination of swelling and mucoadhesive approach: A mechanistic study. Drug Des. Devel. Ther., 2013, 7, 1455-1469.
[] [PMID: 24348022]
Patel, A.K.; Mishra, M.K.; Gupta, J.; Ghoshal, S.; Gupta, R.; Kushwaha, K. Guar gum-based floating microspheres of repaglinide using 32 factorial design: Fabrication, optimization, characterization, and in vivo buoyancy behavior in albino rats. Assay Drug Dev. Technol., 2021, 19(2), 63-74.
[] [PMID: 33090876]
Rajinikanth, P.S.; Karunagaran, L.N.; Balasubramaniam, J.; Mishra, B. Formulation and evaluation of clarithromycin microspheres for eradication of Helicobacter pylori. Chem. Pharm. Bull., 2008, 56(12), 1658-1664.
[] [PMID: 19043235]
Bansal, M.; Verma, R.; Mittal, V.; Kaushik, D. Central composite design for development and evaluation of floating-mucoadhesive tablets of gliclazide. Curr. Drug Ther., 2020, 15, 1-11.
Huang, Y.; Wei, Y.; Yang, H.; Pi, C.; Liu, H.; Ye, Y.; Zhao, L.A. 5-fluorouracil-loaded floating gastroretentive hollow microsphere: Development, pharmacokinetic in rabbits, and biodistribution in tumor-bearing mice. Drug Des. Devel. Ther., 2016, 10, 997-1008.
[] [PMID: 27042001]
Kumari, B.; Khansili, A.; Phougat, P.; Kumar, M. Comprehensive review of the role of acrylic acid derivative polymers in floating drug delivery system. Polim. Med., 2019, 49(2), 71-79.
[] [PMID: 32589822]
Kumari, B.; Pandey, P.; Dureja, H. Formulation and characterization of gastroretentive floating tablets of atorvastatin calcium using central composite design. J. Pharm. Res., 2017, 16(3), 247-256.
Lin, Y.H.; Tsai, S.C.; Lai, C.H.; Lee, C.H.; He, Z.S.; Tseng, G.C. Genipin-cross-linked fucose-chitosan/heparin nanoparticles for the eradication of Helicobacter pylori. Biomaterials, 2013, 34(18), 4466-4479.
[] [PMID: 23499480]
Nama, M.; Gonugunta, C.S.R.; Reddy Veerareddy, P. Formulation and evaluation of gastroretentive dosage forms of Clarithromycin. AAPS PharmSciTech, 2008, 9(1), 231-237.
[] [PMID: 18446486]
Pandey, J.; Shankar, R.; Kumar, M.; Shukla, K.; Kumari, B. Development of nasal mucoadhesive microspheres of granisetron: A potential drug. Drug Res., 2020, 70(8), 367.
[] [PMID: 32559774]
Matharu, A.S.; Motto, M.G.; Patel, M.R.; Simonelli, A.P.; Dave, R.H. Evaluation of hydroxypropyl methylcellulose matrix systems as swellable Gastro-Retentive Drug Delivery Systems (GRDDS). J. Pharm. Sci., 2011, 100(1), 150-163.
[] [PMID: 20572054]
Mishra, S.K.; Gupta, M.K. Characterization and evaluation of nizatidine floating microspheres based drug delivery system for anti-ulcer activity. Int. J. Pharm. Sci. Res., 2019, 10(10), 4557-4567.
Rani, R.; Kumar, M.; Yadav, N.; Bhatt, S.; Malik, A. Recent advances in the development of floating microspheres for the treatment of gastric ulcers. Int. J. Adv. Sci. Tech, 2020, 29(5), 3613-3627.
Farooq, U.; Khan, S.; Nawaz, S.; Ranjha, N.M.; Haider, M.S.; Khan, M.M.; Dar, E.; Nawaz, A. Enhanced gastric retention and drug release via development of novel floating microspheres based on Eudragit E100 and polycaprolactone: Synthesis and in vitro evaluation. Des. Monomers Polym., 2017, 20(1), 419-433.
[] [PMID: 29491813]
Mwila, C.; Walker, R.B. Improved stability of rifampicin in the presence of gastric-resistant isoniazid microspheres in acidic media. Pharmaceutics, 2020, 12(3), 234.
Verma, R.; Kaushik, D. Development, optimization, characterization and impact of in vitro lipolysis on drug release of telmisartan loaded SMEDDS. Drug Deliv. Lett., 2019, 9, 330-340.
Verma, R.; Mittal, V.; Kaushik, D. Quality based design approach for improving oral bioavailability of valsartan loaded SMEDDS and study of impact of lipolysis on the drug diffusion. Drug Deliv. Lett., 2018, 8, 130-139.
Abbas, A.K.; Alhamdany, A.T. Floating microspheres of enalapril maleate as a developed controlled release dosage form: Investigation of the effect of an ionotropic gelation technique. Turk. J. Pharm. Sci., 2020, 17(2), 159-171.
[] [PMID: 32454775]
Jain, A.K.; Sahu, P.; Mishra, K.; Jain, S.K. Repaglinide and metformin loaded amberlite resin based floating microspheres for the effective management of type 2 diabetes. Curr. Drug Deliv., 2021, 18(5), 654-668.
[] [PMID: 33106142]
Park, J.H.; Jang, K.J.; Kim, C.H.; Lee, Y.H.; Lee, S.J.; Kim, B.H.; Yoon, H.M. Ganoderma lucidum pharmaco-puncture for the treatment of acute gastric ulcers in rats. J. Pharmacopuncture, 2014, 17, 40-49.
Ramadan, A.A.; Elbakry, A.M.; Sarhan, H.A.; Ali, S.H. Silymarin loaded floating polymer(s) microspheres: Characterization, in-vitro/in-vivo evaluation. Pharm. Dev. Technol., 2020, 25(9), 1081-1089.
Verma, R.; Kaushik, A.; Almeer, R.; Rahman, M.H.; Abdel-Daim, M.M.; Kaushik, D. Improved pharmacodynamic potential of rosuvastatin by self-nanoemulsifying drug delivery system: An in vitro and in vivo evaluation. Int. J. Nanomedicine, 2021, 16, 905-924.
Kim, E.S.; Kim, D.Y.; Lee, J.S.; Lee, H.G. Mucoadhesive chitosan-gum Arabic nanoparticles enhance the absorption and antioxidant activity of quercetin in the intestinal cellular environment. J. Agric. Food Chem., 2019, 67(31), 8609-8616.
[] [PMID: 31314514]
Ji, J.; He, X.; Yang, X.L.; Du, W.J.; Cui, C.L.; Wang, L.; Wang, X.; Zhang, C.F.; Guo, C.R. The in vitro/vivo evaluation of prepared gastric floating tablets of berberine hydrochloride. AAPS PharmSciTech, 2017, 18(6), 2149-2156.
[] [PMID: 28035611]
Tort, S.; Han, D.; Steckl, A.J. Self-inflating floating nanofiber membranes for controlled drug delivery. Int. J. Pharm., 2020, 579, 119164.
[] [PMID: 32081796]
Hooda, A.; Nanda, A.; Jain, M.; Kumar, V.; Rathee, P. Optimization and evaluation of gastroretentive ranitidine HCl microspheres by using design expert software. Int. J. Biol. Macromol., 2012, 51(5), 691-700.
[] [PMID: 22903013]
Yang, L.; Wang, S.; Ma, Q.; Song, Z.; Hou, R.; Huang, S.; Cheng, D.; Zhang, Z. Fabrication of sulfoxaflor-loaded natural polysaccharide floating hydrogel microspheres against Nilaparvata lugens (Stal) in rice fields. Pest Manag. Sci., 2020, 76(9), 3046-3055.
[] [PMID: 32279438]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy