PREPARATION AND EVALUATION OF CONTROLLED RELEASE FLOATING MICROSPHERES OF REPAGLINIDE: OPTIMIZATION AND IN-VITRO STUDIES
Objective: To develop and evaluate floating microspheres of repaglinide (RG).
Materials and Methods: RG loaded noneffervescent microspheres of different ratios of ethylcellulose (EC) and hydroxypropyl methylcellulose (HPMC
K4M) were prepared using polyvinyl alcohol as emulsifier by solvent evaporation technique. Various process variables such as polymer ratio, stirring
speed, concentration of drug, and emulsifying agent were studied. Compatibility of drug and polymers was studied by Fourier-transform infrared
spectroscopy (FTIR). Characterization, in-vitro evaluation, and kinetic studies were performed.
Results: FTIR spectra have revealed no drug-excipient incompatibility. The average particle size of microspheres was in the range of 312-359 Î¼m. The
results showed that floating microspheres were successfully prepared with good yield (56.15-64.3%), high entrapment efficiency (58.22-70.14%),
and good floating behavior (63.1-76.2%), respectively. In-vitro release data indicates appreciable amount of drug is released (62.28-73.27%) from the
microspheres in gastric fluid. The mechanism of drug release founds to follow first order kinetics (r2=0.986).
Conclusion: The developed floating microspheres of RG may be used for prolonged drug release for at least 12 hrs, thereby improving bioavailability
and patient compliance.
Keywords: Repaglinide, Compatibility, Kinetic, Ethylcellulose.
1. Das AV, Padayatti PS, Paulose CS. Effect of leaf extract of Aegle marmelose (L.) Correa ex Roxb. on histological and ultra-structural changes in tissues of streptozotocin induced diabetic rats. Indian J Exp Biol 1996;34(4):341-5.
2. Cline GW, Petersen KF, Krssak M, Shen J, Hundal RS, Trajanoski Z. Impaired glucose transport as a cause decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes. The New Eng J Med 1991;341(4):240-6.
3. Ronald KC. Pathophysiology of Diabetes Mellitus: An Overview. 2nd ed. New York: Mac Millan Publishing Co.; 1994.
4. Fonseca VA. Defining and characterizing the progression of type 2 diabetes. Diabetes Care 2009;32(2):S151-6.
5. Van Gaal LF, Van Acker KL, De Leeuw IH. Repaglinide improves blood glucose control in sulphonylurea-naive type 2 diabetes. Diabetes Res Clin Pract 2001;53(3):141-8.
6. Fuhlendorff J, Rorsman P, Kofod H, Brand CL, Rolin B, MacKay P, et al. Stimulation of insulin release by repaglinide and glibenclamide involves both common and distinct processes. Diabetes 1998;47(3):345-51.
7. Kumar R, Philip A. Gastroretentive dosage forms for prolonging gastric
Table 2: Results of micromeritics properties
Mean particle size
Angle of repose
Fig. 4: Effect of emulsifier concentration on various optimization parameters. All data are represented as meanÂ±standard deviation (n=3)
Fig. 5: First order plot of optimized formulation (C2)
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Sharma et al.
residence time. Int J Pharm Med 2007;21:157-71.
8. Kotreka UK, Adeyeye MC. Gastroretentive floating drug-delivery systems: A critical review. Cri Rev Ther Drug Car Sys 2011;28(1):47-99.
9. Soppimath KS, Kulkarni AR, Aminabhavi TM. Development of hollow microspheres as floating controlled-release systems for cardiovascular drugs: Preparation and release characteristics. Drug Dev Ind Pharm 2001;27(6):507-15.
10. Singh BN, Kim BH. Floating drug delivery systems: An approach to oral controlled drug delivery via gastric retention. J Contr Rel 2000;63(3):235-59.
11. Kamath S, Kumar S. Design and evaluation of floating microspheres of rabeprazole sodium. Int J Pharm Pharm Sci 2012;4:357-67.
12. Perumandla PK, Sree P. Formulation and in vitro evaluation of floating microspheres of dextromethorphanhydrobromide. Int J Pharm Pharm Sci 2014;6:206-10
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(2):135-40.
14. Patrick JS. Martinâ€™s Physical Pharmacy and Pharmaceutical Sciences. 5th ed. Philadelphia, USA: Lippincott Williams & Wilkins; 2006.
15. Jain SK, Awasthi AM, Jain NK, Agrawal GP. Calcium silicate based microspheres of repaglinide for gastroretentive floating drug delivery: Preparation and in-vitro characterization. J Control Rel 2005;107(2):300-9.
16. Costa P, Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001;13(2):123-33.
17. Streubel A, Siepmann J, Bodmeier R. Gastroretentive drug delivery system. Expert Opin. Drug Deliv 2006;3(2):217-33.
18. Fu X, Ping Q, Gao Y. Effects of formulation factors on encapsulation efficiency and release behavior in vitro of huperzine A-PLGA microspheres. J Microencapsul 2005;22(7):57-66.
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