FORMULATION AND EVALUATION OF METFORMIN HYDROCHLORIDE LOADED FLOATING MICROSPHERES
Objective: The main objective of this study was to develop and evaluate the eudragit and HPMC coated metformin hydrochloride floating microspheres, in which HPMC helps in floating and eudragit as a coating material for a site-specific drug release in a controlled manner and the active moiety metformin used as anti-hyperglycemic agent.
Methods: The floating microsphere was prepared by the solvent evaporation method incorporating metformin as a model drug. The prepared floating microsphere were characterized for particle size, %yield, drug loading and entrapment efficiency, compatibility study, %buoyancy, surface morphology and In vitro drug release and release kinetics.
Results: The result metformin loaded floating microsphere was successfully prepared and the particle size range from 397±23.22 to 595±15.82 µm, the entrapment efficiency range from 83.49±1.33 to 60.02±1.65% and drug loading capacity range from 14.3±0.54 to 13.31±0.47% and %buoyancy range from 85.67±0.58 to 80.67±1.15%. The FT-IR and X-RD analysis confirmed that no any interaction between drug and excipient, and surface morphology confirmed those particles are sphere. The floating microsphere show maximum 96% drug release in pH 0.1N HCL and follow the Korsmeyer peppas model of the super case-2 transport mechanism.
Conclusion: These results suggest that metformin loaded floating microspheres could be retain in stomach for long time and give site specific drug release in controlled manner.
2. Streubel A, Siepmann J, Bodmeier R. Gastroretentive drug delivery system. Expert Opin Drug Delivery 2006;3:217-33.
3. Iannucelli V, Coppi G, Bernabei MT, Camerorni R. Air compartment multiple-unit system for prolonged gastric residence part-Iformulation study. Int J Pharm 1998;174:47-54.
4. Rouge N, Allemann E, Gex-Fabry M, Balant L, Cole ET, Buri P, et al. Comparative pharmacokinetic study of a floating multiple-unit capsule, a high-density multiple unit capsule and an immediate-release tablet containing 25 mg atenolol. Pharm Acta Hel Betiae 1998;73:81-7.
5. Streubel A, Siepmann J, Bodmeier R. Multiple units gastro retentive drug delivery: a new preparation method for low-density microparticles. J Microencapsule 2003;20:329-47.
6. Goole J, Vanderbist F, Aruighi K. Development and evaluation of new multiple-unit levodopa sustained-release floating dosage forms. Int J Pharm 2007;334:35-41.
7. Shrma S, Pawar A. Low-density multiparticulate system for pulsatile release of meloxicam. Int J Pharm 2006;313:150-8.
8. Santus G, Lazzarini G, Bottoni G, Sandefer EP, Page RC, Doll WJ, et al. An in vitro-in vivo investigation of oral bioadhesive controlled release furosemide formulations. Eur J Pharm Biopharm 1997;44:39-52.
9. Klausner EA, Lavy E, Friedman M, Hoffman A. Expandable gastro retentive dosage forms. J Controlled Release 2003;90:143-62.
10. Deshpande AA, Shah N, Rhodes CT, Malik W. Development of a novel controlled-release system for gastric retention. Pharm Res 1997;14:815-9.
11. Park K. Enzyme-digestible swelling as platforms for longterm oral drug delivery: synthesis and characterization. Biomaterials 1988;9:435.
12. Fujimori J, Machida Y, Nagai T. Preparation of a magnetically-responsive tablet and configuration of its gastric residence in beagle dogs. STP Pharma Sci 1994;4:425-30.
13. Kawashima Y, Niwa T, Takeuchi H, Hino T, Itoh Y. Hollow microspheres for use as a floating controlled drug delivery system in the stomach. J Pharm Sci 1992;81:135-40.
14. Lee HJ, Park GT, Choi KH. Development of oral drug delivery system using floating microspheres. J Microencapsulation 1999;16:715-29.
15. Obeidat WM, Price JC. Evaluation of enteric matrix microspheres prepared by emulsion-solvent evaporation using scanning electron microscopy. J Microencap 2004;21:47-57.
16. Subrahmanyam CVS. Textbook of physical pharmaceutics. 2nd ed. Mumbai, India: Vallabh Publication; 2002.
17. Patel A, Ray S, Thakur SR. In vitro evaluation and optimization of controlled release floating drug delivery system of metformin hydrochloride. DARU 2006;14:57–64.
18. Subham B, Gaurav C, Dilip KP. Investigation on cross-linking density for development of novel interpenetrating polymer network (IPN) based formulation. J Sci Ind Res 2010;69:777-84.
19. Swamy SEK, Goud AB. Formulation and evaluation of sustained-release acelofenac microspheres. J Adv Pharm Sci 2012;2:155-66.
20. Shariff A, Manna PK, Paranjothy KL. Entrapment of andrographolide in cross-linked alginate pellets: I. formulation and evaluation of associated release kinetics. Pakistan J Pharm Sci 2007;20:1-9.
21. Ranjha NM, Khan H, Naseem S. Encapsulation and characterization of controlled release flurbiprofen loaded microspheres using beeswax as an encapsulating agent. J Mater Sci Mater Med 2010;21:1621-30.
22. Patel R, Bhimani D, Patel J, Patel D. Solid-state characterization and dissolution properties of ezetimibe–cyclodextrins inclusion complexes. J Incl Phenom Macrocyclic Chem 2008;60:241-51.
23. Mohamed MN, Khaleid MA, Mohamed AS. formulation and evaluation of extended-release metformin hydrochloride beads. Int J Pharm Pharm Sci 2010;6:433-41.
24. Senthil SK, Jaykar B, Kavimani S. Formulation, characterization and in vitro evaluation of floating microsphere containing rabeprazole sodium. J Inn Tre Pharm Sci 2010;1:274-82.
25. Bhardwaj P, Chaurasia D, Singh R, Swarup A. Development and characterization of novel site-specific hollow floating microspheres bearing 5-fu for stomach targeting. Sci World J 2014. http://dx.doi.org/10.1155/2014/705259
26. Kamel HA, Sokar SM, Gamal SS, Naggar FV. Preparation and evaluation of ketoprofen floating oral delivery system. Int J Pharm 2001;220:13-21.
27. Narasimha SDP, Murthay NL, Chowdhury P. Kinetic modelling on drug release from controlled drug delivery system. Acta Pharm 2010;67:217-23.
28. Suleiman NN. The kinetics of drug release from ethylcellulose solid dispersions. Drug Dev Ind Pharm 1985;11:2169-81.
29. Simonelli DS, Higuchi W. Investigation of factors influencing release of solid drug dispersed in inert matrices. J Pharm Sci 1965;54:1459-64.
30. Higuchi T. Mechanism of sustained action medication. Theoretical analysis of the rate of release of solid drugs dispersed in solid matrices. J Pharm Sci 1963;52:1145-9.
31. Patel B, Modi V, Patel K, Patel M. Preparation and evaluation of ethyl cellulose microspheres prepared by an emulsification-solvent evaporation method. Int J Res Management Pharm 2012;1:82-91.
32. Vaghani S, Vasanti S, Chaturvedi K, Satish CS. Stomach-specific drug delivery of 5-fluorouracil using ethylcellulose floating microspheres. Pharm Dev Technol 2010;15:154–61.
33. Farooq U, Khan S, Nawaz S, Ranjha NM. Enhanced gastric retention and drug release via the development of novel floating microspheres based on Eudragit E100 and polycaprolactone: synthesis and in vitro evaluation. Des Monomers Polym 2017;20:419-33.
34. Choudhury PM, Kar M, Chauhan SC. Cellulose acetate microspheres as floating depot systems to increase gastric retention of antidiabetic drug: formulation, characterization and in vitro–in vivo evaluation. Drug Dev Ind Pharm 2008;34:349–54.
35. Ershad S, Sai KV, Kartheek U, Sandeep M, Prameela Rani K. Preparation and evaluation of floating microspheres of ritonavir. J Pharm Pharm Sci 2014;3:5-11.
36. Mahaveer DK, Tejraj MA. Poly (vinyl alcohol) and poly (acrylic acid) sequential interpenetrating network pH-sensitive microspheres for the delivery of diclofenac sodium to the intestine. J Controlled Release 2004;96:9–20.
37. Sharma M. In vitro and in vivo evaluation of repaglinide loaded ?oating microspheres prepared from different viscosity grades of HPMC polymer. Saudi Pharm J 2015. Doi:10.1016/ j.jsps.2015.02.013
38. Dubey M, Kesharwani P, Tiwari A, Chandel R. Formulation and evaluation of floating microsphere containing an anti-diabetic drug. Int J Pharm Chem Sci 2012;1:1038-47.
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