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Micro and Nanosystems

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ISSN (Print): 1876-4029
ISSN (Online): 1876-4037

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Research Article

Experimental Investigation on Efficacy of Eudragit RS 100 Polymer in Prolonging Glibenclamide Release by Intragastric Floating Microsphere Formulation and Physicochemical Evaluation

Author(s): Devika Tripathi*, Princy Yadav, Gauransh Mishra and Awani Kumar Rai

Volume 16, Issue 2, 2024

Published on: 28 March, 2024

Page: [123 - 138] Pages: 16

DOI: 10.2174/0118764029286890240314060427

Price: $65

Abstract

Background: The amalgamation of targeted transportation and enhancement of the release profile of the active pharmaceutical ingredient is a contemporary trend in the evolution of oral medicinal products. A renowned method to actualize this concept is to develop floating gastroretentive delivery systems that ensure an extended stay of the dosage form on the gastric surface. The success of drug delivery is largely dependent on the type of polymer used that sustains the release and avoids any toxic effects. Intragastric floating drug delivery systems are designed to remain buoyant in the stomach without affecting the gastric emptying rate for a prolonged period. This allows for a slow release of the drug in the stomach, which can be particularly beneficial for drugs with a narrow absorption window, like Glibenclamide, an anti-diabetic medication.

Objective: The current research focused on the sustained drug delivery of Glibenclamide as intragastric floating microspheres. The goal was to adjust the floatation and drug release pattern using Eudragit RS 100 and magnesium stearate as a droplet stabilizer. Different batches of floating microspheres were optimized based on the polymer, drug-polymer concentration, and the amount of magnesium stearate. The strategy aimed to enhance the effectiveness of Glibenclamide, particularly for individuals with diabetes, by facilitating a controlled and consistent release of the drug in the gastric environment.

Materials and Methods: The solvent evaporation method was used to create four batches of intragastric microspheres. The maximum absorbance of the drug, also known as lambda max, was observed at 212 nm. The prepared batches were evaluated for various in-vitro physicochemical parameters. The average particle size was found to be 619 nm. Rheological studies indicated excellent flow properties. The microspheres exhibited in-vitro buoyancy for up to 7 hours.

Results: The entrapment efficiency was as high as 93.19%. Scanning Electron Microscopy (SEM) analysis revealed that the microspheres have a porous structure, which allows for the easy movement of solvents and solutes into and out of the microspheres. Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA) indicated the physical and chemical properties of the microspheres. All in-vitro drug release and kinetic studies for the optimized batch (F-M4) revealed that Eudragit RS 100 effectively sustained the intragastric delivery of Glibenclamide.

Conclusion: Floating drug delivery systems enhance oral dosage forms and the range of APIs by ensuring targeted gastric delivery and modified release. This improves bioavailability, reduces drug losses, and partially mitigates side effects.

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[1]
Galicia-Garcia, U.; Benito-Vicente, A.; Jebari, S.; Larrea-Sebal, A.; Siddiqi, H.; Uribe, K.B.; Ostolaza, H.; Martín, C. Pathophysiology of type 2 diabetes mellitus. Int. J. Mol. Sci., 2020, 21(17), 6275.
[http://dx.doi.org/10.3390/ijms21176275] [PMID: 32872570]
[2]
Leão, A.D.; Oliveira, V.V.; Marinho, F.A.; Wanderley, A.G.; Aguiar, J.S.; Silva, T.G.; Soares, M.F.R.; Soares-Sobrinho, J.L. Hybrid systems of glibenclamide and layered double hydroxides for solubility enhancement for the treatment of diabetes mellitus II. Appl. Clay Sci., 2019, 181, 105218.
[http://dx.doi.org/10.1016/j.clay.2019.105218]
[3]
Rambiritch, V.; Maharaj, B.; Naidoo, P. Glibenclamide in patients with poorly controlled type 2 diabetes: A 12-week, prospective, single-center, open-label, dose-escalation study. Clin. Pharmacol., 2014, 6, 63-69.
[4]
Adepu, S.; Ramakrishna, S. Controlled drug delivery systems: Status and future directions. Molecules, 2021, 26(19), 5905.
[http://dx.doi.org/10.3390/molecules26195905] [PMID: 34641447]
[5]
Baig, N.; Kammakakam, I.; Falath, W. Nanomaterials: A review of synthesis methods, properties, recent progress, and challenges. Mater. Adv., 2021, 2(6), 1821-1871.
[http://dx.doi.org/10.1039/D0MA00807A]
[6]
Kumar, A.; Srivastava, R. In vitro in vivo studies on floating microspheres for gastroretentive drug delivery system: A review. Asian J. Pharm. Clin. Res., 2021, 13-26.
[7]
Singh, M.N.; Hemant, K.S.; Ram, M.; Shivakumar, H.G. Microencapsulation: A promising technique for controlled drug delivery. Res. Pharm. Sci., 2010, 5(2), 65-77.
[PMID: 21589795]
[8]
Veiseh, O.; Tang, B.C.; Whitehead, K.A.; Anderson, D.G.; Langer, R. Managing diabetes with nanomedicine: Challenges and opportunities. Nat. Rev. Drug Discov., 2015, 14(1), 45-57.
[http://dx.doi.org/10.1038/nrd4477] [PMID: 25430866]
[9]
Saxena, A.; Gaur, K.; Singh, V.; Singh, R.K.; Dashora, A. Floating microspheres as drug delivery system. Amer. J. Pharma. Pharma. Sci., 2014, 1(2), 27-36.
[http://dx.doi.org/10.12966/ajpps.06.02.2014]
[10]
Kakkar, V.; Wani, S.U.D.; Gautam, S.P.; Qadrie, Z.L. Role of microspheres in novel drug delivery systems: Preparation methods and applications. Int. J. Curr. Pharm. Res., 2020, 12(3), 10-15.
[http://dx.doi.org/10.22159/ijcpr.2020v12i3.38326]
[11]
Saini, S.; Asija, R.; Goyal, A. Floating microsphere as gastro retentive drug delivery system: An updated review. Trop. J. Pharma. Life Sci., 2022, 9(2), 21-29.
[12]
Lal, J.S.; Radha, D.; Devaky, K.S. Drug release studies of metformin hydrochloride from chitosan Mango leaf extract microspheres. J. Drug Deliv. Sci. Technol., 2023, 84, 104524.
[http://dx.doi.org/10.1016/j.jddst.2023.104524]
[13]
Jagtap, Y.M.; Ranade, A.N.; Ranpise, N.S.; Bhujbal, R.K. Effect of various polymers concentrations on physicochemical properties of floating microspheres. Indian J. Pharm. Sci., 2012, 74(6), 512-520.
[http://dx.doi.org/10.4103/0250-474X.110578] [PMID: 23798776]
[14]
Ali, R; Aamir, MN; Bilal, M Gastroretentive floating microspheres for the management hypertension based on drug combination of amlodipine /losartan. J. contem. pharma., 2022, 5(2), 40-52.
[15]
Yeni̇lmez, E. Desloratadine-eudragit®RS100 nanoparticles: Formulation and characterization. Turk. J. Pharm. Sci., 2017, 14(2), 148-156.
[http://dx.doi.org/10.4274/tjps.52523] [PMID: 32454606]
[16]
Barnabas, W. Development and evaluation of eudragit floating microspheres containing ezetimibe. J. Cardio. Dis. Res., 2021, 12(4)
[17]
Chaves, P.D.S.; Frank, L.A.; Frank, A.G.; Pohlmann, A.R.; Guterres, S.S.; Beck, R.C.R. Mucoadhesive properties of Eudragit® RS100, Eudragit® S100, and Poly (ε-caprolactone) nanocapsules: Influence of the vehicle and the mucosal surface. AAPS PharmSciTech, 2018, 19(4), 1637-1646.
[http://dx.doi.org/10.1208/s12249-018-0968-5] [PMID: 29500762]
[18]
Kotagale, N.R.; Khandelwal, H.M.; Parkhe, A.P.; Umekar, M.J.; Umekar, M.J. Ranitidine hydrochloride-loaded ethyl cellulose and eudragit Rs 100 buoyant microspheres: Effect of ph modifiers. Indian J. Pharm. Sci., 2011, 73(6), 626-633.
[http://dx.doi.org/10.4103/0250-474X.100236] [PMID: 23112396]
[19]
Kashif, P.M.; Madni, A.; Ashfaq, M.; Rehman, M.; Mahmood, M.A.; Khan, M.I.; Tahir, N. Development of Eudragit RS 100 microparticles loaded with ropinirole: Optimization and in vitro evaluation studies. (“Statistically optimized pentazocine loaded microsphere for the... - PLOS”). AAPS PharmSciTech, 2017, 18(5), 1810-1822.
[http://dx.doi.org/10.1208/s12249-016-0653-5] [PMID: 27830514]
[20]
National library of medicine 2004. Available from: https://www.nlm.nih.gov/ (Accessed on 2023 June 18).
[21]
Kumar, L.; Meel, R.K. Formulation and evaluation of floating microspheres of glibenclamide using muco-adhesive polymers by ion gelation method. J. Drug Deliv. Ther., 2022, 12(1), 136-141.
[22]
Rathor, S.; Bhatt, D.C. Novel glibenclamide–phospholipid complex for diabetic treatment: Formulation, physicochemical characterization, and in-vivo evaluation. Indian J. Pharma. Edu. Res., 2022, 56(3), 697-705.
[http://dx.doi.org/10.5530/ijper.56.3.118]
[23]
Venkateswarlu, K. Evaluation of glibenclamide microspheres for sustained release. J. Pharm. Pharmacogn. Res., 2017, 5(1), 78-87.
[http://dx.doi.org/10.56499/jppres16.156_5.2.78]
[24]
Saputri, FA; Hasanah, AN; Rusdiana, T; Surono, IS; Abdulah, R A sensitive bioanalytical method for the simultaneous determination of amlodipine and glibenclamide. Pharma. Sci. Asia, 2022, 49(4)
[http://dx.doi.org/10.29090/psa.2022.04.22.095]
[25]
Dahlgren, D.; Cano-Cebrián, M.J.; Olander, T.; Hedeland, M.; Sjöblom, M.; Lennernäs, H. Regional intestinal drug permeability and effects of permeation enhancers in rat. Pharmaceutics, 2020, 12(3), 242.
[http://dx.doi.org/10.3390/pharmaceutics12030242] [PMID: 32182653]
[26]
Kedia, K.; Wairkar, S. Improved micromeritics, packing properties and compressibility of high dose drug, Cycloserine, by spherical crystallization. Powder Technol., 2019, 344, 665-672.
[http://dx.doi.org/10.1016/j.powtec.2018.12.068]
[27]
Caputo, F.; Clogston, J.; Calzolai, L.; Rösslein, M.; Prina-Mello, A. Measuring particle size distribution of nanoparticle enabled medicinal products, the joint view of EUNCL and NCI-NCL. A step by step approach combining orthogonal measurements with increasing complexity. J. Control. Release, 2019, 299, 31-43.
[http://dx.doi.org/10.1016/j.jconrel.2019.02.030] [PMID: 30797868]
[28]
Nguyen, N.N.T.; Pham, D.T.; Nguyen, D.T.; Trinh, T.T.L. Bilayer tablets with sustained-release metformin and immediate-release sitagliptin: Preparation and in vitro/in vivo evaluation. J. Pharm. Investig., 2021, 51(5), 579-586.
[http://dx.doi.org/10.1007/s40005-021-00533-z]
[29]
Aleti, R.; Baratam, E.R. Formulation and evaluation of metformin hydrochloride and gliclazide sustained release bilayer tablets: A combination therapy in management of diabetes. Intern. J. Appl. Pharma., 2021, 51, 343-350.
[30]
Kakad, S.B.; Rachh, P.R. Effect of hydrophilic polymer and binder on drug release of metformin HCl sustained release tablet. Int. J. Health Sci., 2022, (III), 6635-3343.
[http://dx.doi.org/10.53730/ijhs.v6nS3.7478]
[31]
Nikhilitha, P. Effect of natural polymer on release retarding rate of glimepiride sustained release tablet. Int. J. Adv. Sci. Res., 2021, 12(01), 145-150.
[32]
Rohilla, S.; Bhatt, D.C.; Ahalwat, S. Fabrication of potential gastroretentive microspheres of itraconazole for stomach-specific delivery: Statistical optimization and in vitro evaluation. J. Appl. Pharm. Sci., 2020, 10(3), 119-127.
[http://dx.doi.org/10.7324/JAPS.2020.103016]
[33]
Patil, S.; Pawar, S. Formulation and process optimization of polymeric microsphere formulation of Glibenclamide using solvent evaporation technique. Eur. Chem. Bull., 2023, 12(4), 3000-3018.
[34]
Patel, B.; Kushwaha, R.S.; Jain, S. Formulation, development, and evaluation of floating microsphere of losartan potassium using natural polymer. J. Drug Deliv. Ther., 2019, 9(3-s), 223-228.
[35]
Ambreen, T.; Kim, M.H. Influence of particle size on the effective thermal conductivity of nanofluids: A critical review. Appl. Energy, 2020, 264, 114684.
[http://dx.doi.org/10.1016/j.apenergy.2020.114684]
[36]
Manubolu, K.; Munna, S.; Bonnoth, CK; Mohan, GR Int. J. Life Sci. Pharma Res., 2021, 11(1), 166-183.
[37]
Saravanakumar, K.; Thulluru, A.; Samineni, R.; Ishwarya, M.; Nagaveni, P.; Mahammed, N. Effect of sodium alginate in combination with natural and synthetic polymers on the release of verapamil hcl from its floating microspheres. J. Pharma. Sci. Res., 2019, 11(5), 2028-2035.
[38]
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.
[http://dx.doi.org/10.4274/tjps.galenos.2018.15046] [PMID: 32454775]
[39]
Barhate, AN; Shinde, TS; Rampure, PS Formulation and evaluation of floating microspheres of lansoprazole. Indian Drugs, 2022, 59(3)
[http://dx.doi.org/10.53879/id.59.03.12444]
[40]
Mohamed, J.M.M.; Mahajan, N.; El-Sherbiny, M.; Khan, S.; Al-Serwi, R.H.; Attia, M.A.; Altriny, Q.A.; Arbab, A.H. Ameliorated stomach specific floating microspheres for emerging health pathologies using polymeric Konjac glucomannan-based Domperidone. BioMed Res. Int., 2022, 2022, 1-12.
[http://dx.doi.org/10.1155/2022/3670946] [PMID: 35872840]
[41]
Patel, A.K.; Mishra, M.K.; Gupta, J.; Ghoshal, S.; Gupta, R.; Kushwaha, K. Guar Gum-based floating microspheres of repaglinide using 32 factorial designs: Fabrication, optimization, characterization, and in vivo buoyancy behavior in albino rats. Assay Drug Dev. Technol., 2021, 19(2), 63-74.
[http://dx.doi.org/10.1089/adt.2020.1006] [PMID: 33090876]
[42]
An, Y.; Zheng, H.; Zheng, X.; Sun, Q.; Zhou, Y. Use of a floating adsorbent to remove dyes from water: A novel efficient surface separation method. J. Hazard. Mater., 2019, 375, 138-148.
[http://dx.doi.org/10.1016/j.jhazmat.2019.04.060] [PMID: 31054531]
[43]
Huanbutta, K.; Sangnim, T. Design and development of zero-order drug release gastroretentive floating tablets fabricated by 3D printing technology. J. Drug Deliv. Sci. Technol., 2019, 52, 831-837.
[http://dx.doi.org/10.1016/j.jddst.2019.06.004]
[44]
Bhise, M.; Shukla, K. Development and evaluation of floating microspheres of anticonvulsant drug by 32 full factorial design. Turk J. Pharm. Sci., 2023, 19(5), 595-602.
[45]
Gada, S.G.; y, A., Setty C.M. Drumstick mucilage microspheres for controlled release of lamivudine: Design, optimization, and in vitro evaluation. Int. J. Pharm. Pharm. Sci., 2019, 60-68.
[http://dx.doi.org/10.22159/ijpps.2019v11i4.30733]
[46]
Yadav, R.; Bhowmick, M.; Rathi, V.; Rathi, J. Design, and characterization of floating microspheres for rheumatoid arthritis. J. Drug Deliv. Ther., 2019, 9(2-s), 76-81.
[47]
Pawar, P.; Duduskar, A.; Waydande, S. Design and evaluation of eudragit rs-100 based itraconazole nanosuspension for ophthalmic application. Curr. Drug Res. Rev., 2021, 13(1), 36-48.
[http://dx.doi.org/10.2174/2589977512666200929111952] [PMID: 32990554]
[48]
Jain, V.; Singh, R. Development and characterization of eudragit RS 100 loaded microsponges and its colonic delivery using natural polysaccharides. Acta Pol. Pharm., 2010, 67(4), 407-415.
[PMID: 20635537]
[49]
AL-Hussein, A.B.A.; Rahma, F.; Fortuna, L.; Bucolo, M.; Frasca, M.; Buscarino, A. A new time-delay model for chaotic glucose-insulin regulatory system. Int. J. Bifurcat. Chaos, 2020, 30(12), 2050178.
[http://dx.doi.org/10.1142/S0218127420501783]

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