ENHANCEMENT OF THERAPEUTIC WINDOW OF METFORMIN HYDROCHLORIDE BY FABRICATION OF MICROSPHERES COMPRISING POLYMERIC INCULCATION WITH SEMI-SYNTHETIC AND SYNTHETIC POLYMERS BY IMPLEMENTATION OF BOX-BEHNKEN DESIGN

Authors

  • MD AAMER QUAZI K. T. Patil College of Pharmacy, Osmanabad, Maharashtra, India
  • NAZIA KHANAM Research Scholar, Faculty of Science and Technology (Pharmacy), Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India, Malla Reddy Institute of Pharmaceutical Sciences, Hyderabad, Telangana State, India

DOI:

https://doi.org/10.22159/ijap.2021v13i4.41225

Keywords:

Box-behnken design, Controlled release system, Kollidon SR, Metformin hydrochloride, Nuclear magnetic resonance

Abstract

Objective: Innovative enhancement of therapeutic window of Metformin hydrochloride (MFH) and bioavailability through mucoadhesive microspheres by polymeric inculcation of hydroxypropyl methylcellulose K4M grade (HPMC K4M), hydroxypropyl methylcellulose K100M grade (HPMC K100M) and Kollidon SR grade (KS).

Methods: Controlled release system was developed by incorporating semi-synthetic and synthetic polymers by modified solvent evaporation technique. Fabrication of mucoadhesive microspheres was designed by the implementation of experimental designs to obtain most optimum concentration of selected factors. The method was optimized by Box Behnken design (BBD) with selected factors as concentrations of semi-synthetic and synthetic polymer with stirring speed influence for the obtained responses that were mean particle size (Y1) entrapment efficiency of drug (Y2) and percent mucoadhesion (Y3). Microspheres were characterized for particle size, entrapment efficiency of drug, ex-vivo mucoadhesion study, in vitro study, Fourier transform infrared spectroscopy (FTIR), x-ray diffraction (XRD) detection and H1 Nuclear magnetic resonance (NMR) quantification for optimized formulation.

Results: Implementation of response surface method software for BBD yielded stable microspheres with mean particle size 274 µm, entrapment efficiency of drug 85.07% and percent mucoadhesion 67.03% for optimized formulation F5.

Conclusion: Bridging of MFH with the highly innovative combination of semi-synthetic and synthetic polymers yielded stable, cost-effective microspheres with improved bioavailability with controlled-release effect as till date no literature is available that provide information with selected polymeric combination and analytical characterization.

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References

Hermann LS, Melander A. Biguanides, basic aspects and clinical use in international textbook of diabetes mellitus. KG Alberti. editors. Wiley: New York; 1992. p. 772–95.

Dunn JC, Peters DH. Metformin: a review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus. Drugs 1995;49:721–49.

Wiley A. Insulin and oral hypoglycemic drugs. Williams DA, Lemke TL. editors. Foyes Principle of medicinal chemistry: New York; 2002. p. 641-8.

Chakra BK, Karan S, Das B, Debnath S, Chatterjee TK. A controlled release microsphere formulation of an anti-diabetic drug and characterization of the microsphere. Int J Pharm Pharm Sci 2018;10:30-8.

Hundal RS, Inzucchi SE. Metformin: New understandings, new uses. Drugs 2003;63:1879–94.

Kidson W. Polycystic ovary syndrome: a new direction in treatment. Med J Aust 1998;169:537–40.

Sahra IB, Brustel YLM, Tanti JF, Bost F. Metformin in cancer therapy: a new perspective for an old antidiabetic drug. Mol Cancer Ther 2010;9:1092–9.

Esteghamati A, Eskandari D, Mirmiranpour H, Noshad S, Mousavizadeh M, Hedayati M, et al. Effects of metformin on markers of oxidative stress and antioxidant reserve in patients with newly diagnosed type 2 diabetes: a randomized clinical trial. Clin Nutr 2013;32:179–85.

Roussel R, Travert F, Pasquet B. Reduction of atherothrombosis for continued health registry investigators: metformin use and mortality among patients with diabetes and atherothrombosis. Arch Intern Med 2010;170:1892–9.

Rangel ES, Inzucchi SE. Metformin: clinical use in type 2 diabetes. Diabetologia 2017;60:1586-93.

Scarpello JH, Howlett HC. Metformin therapy and clinical uses. Diab Vasc Dis Res 2008;5:157–67.

Wilcock C, Bailey CJ. Sites of metformin-stimulated glucose metabolism. Biochem Pharmacol 1990;39:1831–4.

Laurence LB, Johns L, Keith LP. 11th edition Goodman and gillman: the pharmacological basis of therapeutics; 2007.

Siepmann J, Peppas NA. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Delivery Rev 2012;64:163–74.

Ige PP, Gattani S. Development of low density microspheres of metformin hydrochloride using ethyl cellulose and HPMC K4M: in vitro and in vivo characterization. Polymer Plast Tech Eng 2012;51:1537-44.

Chen C, Han CH, Sweeney M, Cowles VE. Pharmacokinetics, efficacy, and tolerability of a once daily gastroretentive dosage form of gabapentin for the treatment of postherpetic neuralgia. J Pharm Sci 2013;102:1155-64.

Jagtap P, Tagad R, Shendge R. A brief review on Kollidon. J Drug Delivery Ther 2019;9:493-500.

Sakr W, Alanazi F, Sakr A. Effect of kollidon®SR on the release of albuterol sulphate from matrix tablets. Saudi Pharm J 2011;19:19–27.

Sarkar D, Nandi G, Changder A, Hudati P, Sarkar S, Ghosh LK. Sustained release gastroretentive tablet of metformin hydrochloride based on poly (acrylic acid)‐grafted‐gellan. Int J Biol Macromol 2017;96:137–48.

Russo E, Selmin F, Baldassari S, Gennari CGM, Caviglioli G, Cilurzo F, et al. A focus on mucoadhesive polymers and their application in buccal dosage forms. J Drug Delivery Sci Technol 2016;32:113–25.

Menchicchi B, Fuenzalida JP, Hensel A, Swamy MJ, David L, Rochas C, et al. Biophysical analysis of the molecular interactions between polysaccharides and mucin. Biomacromolecules 2015;16:924–35.

Karna S, Agrawal VK, Chaturvedi S, Alim M. Swellable and floating gastroretentive formulation for sustained delivery of metformin HCL. Int J Pharm Sci Res 2016;7:1590-602.

Quazi MA, Khanam N, Tigote RM. Fabrication and characterization of metformin hydrochloride loaded microspheres by incorporating natural and synthetic polymers for comparative analysis. Int J Pharm Sci Res 2020;11:6539-49.

Alam MI, Siddiqui AR, Khanam N, Kamaruddin SJ. A multivariate quantification of box-behnken design assisted method development and validation of dextromethorphan hydrobromide and desloratadine simultaneously by reverse-phase HPLC in in-house syrup formulation. J Sep Sci 2020;43:1-10.

Deshmukh RK, Naik JB. Aceclofenac microspheres, quality by design approach. Mater Sci Eng C Mater Biol Appl 2014;36:320-8.

Khanam N, Alam MI, Ali QI, Siddiqui AR. A review on optimization of drug delivery system with experimental designs. Int J Appl Pharm 2018;10:7-12.

Maulvi FA, Thakkar VT, Soni TG, Gandhi TR. Optimization of aceclofenac solid dispersion using box-behnken design: in vitro and in vivo evaluation. Curr Drug Delivery 2014;11:380-91.

Khanam N, Alam MI, Sachan AK, Gangwar SS, Anand C. Design and characterization of mucoadhesive microspheres of novel NSAID drug using algino-eudragit RS 100 system. Der Pharm Sin 2011;2:182-91.

Khanam N, Alam IM, Sachan KA, Gangwar S. Fabrication and evaluation of propranolol hydrochloride loaded microspheres by ionic-gelation technique. Der Pharm Lett 2012;4:815-20.

Ige PP, Gattani SG. Design and in vitro and in vivo characterization of mucoadhesive matrix pellets of metformin hydrochloride for oral controlled release: a technical note. Arch Pharm Res 2012;35:487-98.

Kesharvani S, Jaiswal PK, Mukerjee A, Singh AK. Formulation and evaluation of metformin hydrochloride loaded floating microspheres. Int J Pharm Pharm Sci 2020;12:74-82.

Published

07-07-2021

How to Cite

QUAZI, M. A., & KHANAM, N. (2021). ENHANCEMENT OF THERAPEUTIC WINDOW OF METFORMIN HYDROCHLORIDE BY FABRICATION OF MICROSPHERES COMPRISING POLYMERIC INCULCATION WITH SEMI-SYNTHETIC AND SYNTHETIC POLYMERS BY IMPLEMENTATION OF BOX-BEHNKEN DESIGN. International Journal of Applied Pharmaceutics, 13(4), 257–264. https://doi.org/10.22159/ijap.2021v13i4.41225

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