Login Register Cart 0
Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Repaglinide and Metformin-Loaded Amberlite Resin-Based Floating Microspheres for the Effective Management of Type 2 Diabetes

Author(s): Akhlesh K. Jain*, Praveen Sahu, Keerti Mishra and Sunil K. Jain

Volume 18, Issue 5, 2021

Published on: 25 October, 2020

Page: [654 - 668] Pages: 15

DOI: 10.2174/1567201817666201026105611

Price: $65

Abstract

Background: Low bioavailability of anti-diabetic drugs results in the partial absorption of the drug as they are mainly absorbed from the stomach and the lower part of the GIT. Drug bioavailability of anti-diabetic drugs can be significantly increased by prolonging gastric retention time through gastro-retentive dosage form such as floating microspheres.

Objective: The study was aimed to develop and characterize resin based floating microspheres of Repaglinide and Metformin for superior and prolonged maintenance of normoglycaemia in type-2 diabetes mellitus.

Methods: Repaglinide and metformin were complexed with amberlite resin; later resin complexed drug was encapsulated in Ethylcellulose floating microspheres. Floating microspheres were characterized for morphology, particle size, IR spectroscopy, DSC, in vitro release and buoyancy studies. Further, floating microspheres were tested for in vivo blood glucose reduction potential in Streptozocin- induced diabetic mice.

Results: Floating microspheres had a spherical shape and slightly rough surface with the entrapment efficiency in a range of 49-78% for metformin and 52-73% for repaglinide. DSC studies revealed that no chemical interaction took place between polymer and drugs. Floating microspheres showed good buoyancy behavior (P<0.05) and prolonged drug release as compared to plain drug (P<0.05). The blood glucose lowering effect of floating microspheres on Streptozocin induced diabetic rats was significantly greater (P<0.05) and prolonged (˃12h) and normoglycaemia was maintained for 6hr.

Conclusion: Floating microspheres containing drug resin complex were able to prolong drug release in an efficient way for a sustained period of time; as a result, profound therapeutic response was obtained.

Keywords: Repaglinide, metformin, amberlite, floating microspheres, diabetes mellitus, IR spectroscopy.

« Previous
Graphical Abstract

[1]
Kharroubi, A.T.; Darwish, H.M. Diabetes mellitus: the epidemic of the century. World J. Diabetes, 2015, 6(6), 850-867.
[http://dx.doi.org/10.4239/wjd.v6.i6.850] [PMID: 26131326]
[2]
Bilous, R.; Donnelly, R. Handbook of diabetes. Wiley-Blackwell, 2010, pp. 9-15.
[http://dx.doi.org/10.1002/9781444391374.ch3]
[3]
Baynest, H.W. Classification, pathophysiology, diagnosis and management of diabetes mellitus. Baynes J. Diabetes Metab., 2015, 6(5), 1-9.
[http://dx.doi.org/10.4172/2155-6156.1000541]
[4]
International diabetes federation. Diabetes Atlas, 8th Ed.; Brussels: Belgium: Int. Diab. Federat., 2017.
[5]
Saeedi, P.; Petersohn, I.; Salpea, P.; Malanda, B.; Karuranga, S.; Unwin, N.; Colagiuri, S.; Guariguata, L.; Motala, A.A.; Ogurtsova, K.; Shaw, J.E.; Bright, D.; Williams, R. IDF Diabetes Atlas Committee. On behalf of the IDF Diabetes Atlas Committee, Global and regional Diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas Diabetes Res, 9th Ed; Clin. Pract, 2019, 157, p. 107843.
[6]
Singh, M.N.; Hemant, K.S.Y.; Ram, M.; Shivakumar, H.G. Microencapsulation: A promising technique for controlled drug delivery. Res. Pharm. Sci., 2010, 5(2), 65-77.
[PMID: 21589795]
[7]
Javiya, C.; Jonnalagadda, S. Physicochemical characterization of spray-dried PLGA/PEG microspheres, and preliminary assessment of biological response. Drug Dev. Ind. Pharm., 2016, 42(9), 1504-1514.
[http://dx.doi.org/10.3109/03639045.2016.1151030] [PMID: 26902521]
[8]
Diwedi, R.; Alexandar, A.; Chandrasekar, M.J.N. Preparation and in vitro evaluation of sustained release tablet Formulations of metformin HCL. Asian J. Pharm. Clin. Res., 2012, 5, 45-48.
[9]
Tripathi, K.D. Essentials of medical pharmacology.JP Medical Ltd, 7th ed; JP Medical Ltd, 2013, p. 275.
[10]
Amidon, G.L.; Lennernäs, H.; Shah, V.P.; Crison, J.R. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm. Res., 1995, 12(3), 413-420.
[http://dx.doi.org/10.1023/A:1016212804288] [PMID: 7617530]
[11]
Harvey, R.A.; Clark, M.A.; Finke, R.; Rey, J.A.; Whalen, K. Lippincott’s illustrated reviews: pharmacology. Wolters Kluwer: Philadelphia, 2012.
[12]
https://www.centerwatch.com/directories/1067-fda-approved- drugs/listing/4024-prandin
[13]
National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 65981, Repaglinide. Retrieved April 16, 2021 from https://pubchem.ncbi.nlm.nih.gov/compound/Repaglinide
[14]
Van Gaal, L.F.; Van Acker, K.L.; De Leeuw, I.H. Repaglinide improves blood glucose control in sulphonylurea-naive type 2 diabetes. Diabetes Res. Clin. Pract., 2001, 53(3), 141-148.
[http://dx.doi.org/10.1016/S0168-8227(01)00253-4] [PMID: 11483229]
[15]
Davis, S.N.; Graner, D.K. Insulin oral hypoglycemic agents and the pharmacology of the pancreas in Godman and Gilman’s: the pharmacological basis of therapeutics.McGraw-Hill Medical Publishing Division: USA, 2001, pp. 1704-1705.
[16]
Dunn, C.J.; Peters, D.H. Metformin. A review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus. Drugs, 1995, 49(5), 721-749.
[http://dx.doi.org/10.2165/00003495-199549050-00007] [PMID: 7601013]
[17]
Senthil Rajan, D.; Mandal, U.K.; Veeran Gowda, K.; Bose, A.; Ganesan, M.; Pal, T.K. Oral delivery system of insulin microspheres: effect on relative hypoglycemia of diabetic albino rats. Boll. Chim. Farm., 2004, 143(8), 315-318.
[PMID: 15884295]
[18]
Melikian, C.; White, T.J.; Vanderplas, A.; Dezii, C.M.; Chang, E. Adherence to oral antidiabetic therapy in a managed care organization: a comparison of monotherapy, combination therapy, and fixed-dose combination therapy. Clin. Ther., 2002, 24(3), 460-467.
[http://dx.doi.org/10.1016/S0149-2918(02)85047-0] [PMID: 11952029]
[19]
Khatri, S.; Awasthi, R. Piperine containing floating microspheres: an approach for drug targeting to the upper gastrointestinal tract. Drug Deliv. Transl. Res., 2016, 6(3), 299-307.
[http://dx.doi.org/10.1007/s13346-016-0285-z]
[20]
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]
[21]
Thombre, N.A.; Gide, P.S. Floating-bioadhesive gastroretentive Caesalpinia pulcherrima-based beads of amoxicillin trihydrate for Helicobacter pylori eradication. Drug Deliv., 2016, 23(2), 405-419.
[http://dx.doi.org/10.3109/10717544.2014.916766] [PMID: 24870198]
[22]
Dong, K.; Zhang, H.; Yan, Y.; Sun, J.; Dong, Y.; Wang, K.; Zhang, L.; Shi, X.; Xing, J. Improvement of side-effects and treatment on the experimental colitis in mice of a resin microcapsule-loading hydrocortisone sodium succinate. Drug Dev. Ind. Pharm., 2017, 43(3), 448-457.
[http://dx.doi.org/10.1080/03639045.2016.1258410] [PMID: 27819157]
[23]
Yu, L.; Li, S.; Yuan, Y.; Dai, Y.; Liu, H. The delivery of ketoprofen from a system containing ion-exchange fibers. Int. J. Pharm., 2006, 319(1-2), 107-113.
[http://dx.doi.org/10.1016/j.ijpharm.2006.03.039] [PMID: 16701973]
[24]
Jaskari, T.; Vuorio, M.; Kontturi, K.; Urtti, A.; Manzanares, J.A.; Hirvonen, J. Controlled transdermal iontophoresis by ion-exchange fiber. J. Control. Release, 2000, 67(2-3), 179-190.
[http://dx.doi.org/10.1016/S0168-3659(00)00204-2] [PMID: 10825552]
[25]
Jeong, S.H.; Park, K. Development of sustained release fast-disintegrating tablets using various polymer-coated ion-exchange resin complexes. Int. J. Pharm., 2008, 353(1-2), 195-204.
[http://dx.doi.org/10.1016/j.ijpharm.2007.11.033] [PMID: 18164882]
[26]
Jain, S.K.; Sahoo, A.K.; Gupta, M.; Pandey, A.N.; Kumar, A.; Jain, A.K. Delivery of repaglinide-cholestyramine complex loaded ethylcellulose microspheres to gastric mucosa for effective management of type-2 diabetes mellitus. Curr. Sci., 2014, 106(11), 1518-1528.
[27]
Mohalkar, A.V.; Attar, M.S.; Banode, S.; Jadhav, A.R.; Wandhre, M.D. Development of formulation and evaluation of metformin HCl SR tablet. Mater. Sci., 2014.
[28]
Porwal, A.; Dwivedi, H.; Pathak, K. Decades of research in drug targeting using gastroretentive drug delivery systems for antihypertensive therapy. Braz. J. Pharm. Sci., 2017, 53(3), e00173.
[http://dx.doi.org/10.1590/s2175-97902017000300173]
[29]
Flanagan, T.L.; Sax, M.F.; Heming, A.E. Toxicity studies on amberlite XE-96, a carboxylic type cation exchange resin. J. Pharmacol. Exp. Ther., 1951, 103(3), 215-221.
[PMID: 14898436]
[30]
Wu, J.H.; Wang, X.J.; Li, S.J.; Ying, X.Y.; Hu, J.B.; Xu, X.L.; Kang, X.Q.; You, J.; Du, Y.Z. Preparation of ethyl cellulose microspheres for sustained release of sodium bicarbonate. Indian J. Pharm. Sci., 2019, 18(2), 556-568.
[PMID: 31531041]
[31]
Qin, C.; He, W.; Zhu, C.; Wu, M.; Jin, Z.; Zhang, Q.; Wang, G.; Yin, L. Controlled release of metformin hydrochloride and repaglinide from sandwiched osmotic pump tablet. Int. J. Pharm., 2014, 466(1-2), 276-285.
[http://dx.doi.org/10.1016/j.ijpharm.2014.03.002] [PMID: 24607209]
[32]
Goode, G.A.; Wagh, S.J.; Irby, D.J.; Ma, D.; Jacobs, R.F.; Kearns, G.L.; Almoazen, H. Bioavailability testing of a newly developed clindamycin oral suspension in a pediatric porcine model. Pharm. Dev. Technol., 2019, 24(8), 1038-1043.
[http://dx.doi.org/10.1080/10837450.2019.1624771] [PMID: 31134840]

Rights & Permissions Print Cite
Article Metrics
10
© 2024 Bentham Science Publishers | Privacy Policy