ETHYLCELLULOSE FLOATING MICROSPHERES OF ANTIDIABETIC AGENT: IN VITRO AND IN VIVO EVALUATION
Keywords:Microsphere, Buoyancy, Emulsifier, Repaglinide
Objective: To develop and evaluate floating type gastro-retentive dosage form, appropriate for controlled release of repaglinide (RG) having a narrow therapeutic window.
Methods: Repaglinide loaded microspheres (MS) using biological macromolecule ethylcellulose (EC) was prepared by a solvent diffusion-evaporation technique using polyvinyl alcohol (PVA) emulsifier. Compatibility of drug and polymer was studied by Fourier-transform infrared spectroscopy (FTIR). During formulation, various process optimisation parameters studied were stirring speed, the concentration of drug, polymer and emulsifier. Characterization and in vitro evaluation was performed. In vivo antidiabetic activity was performed on alloxan induced diabetic rats followed by histopathological screening.
Results: The average particle size was in the range of 174-243 Âµm. Yield, entrapment and buoyancy of microspheres were 68.4ÂÂ-79.8, 58.6-73.1 and 71.8-84.1% respectively. 65.1% release of drug from optimised formulation was obtained which follows first-order kinetics (r2 = 0.989). Optimised formulation treated group shows significant (p<0.01) decrease in glucose level of blood as compared to pure drug treated group during the later hours of study with satisfactory results of histology.
Conclusion: The investigation revealed the promising potential of gastro retentive microspheres for delivering RG for the treatment of non-insulin dependent diabetes mellitus (NIDDM).
Moes AJ. Gastroretentive dosage forms. Crit Rev Ther Drug Carrier Syst 1993;10:143-95.
Desai S, Bolton S. A floating controlled-release drug delivery system: in vitro-in vivo evaluation. Pharm Res 1993;10:1321-5.
Chueh HR, Zia H, Rhodes CT. Optimisation of sotalol floating and bioadhesive extended release tablet formulations. Drug Dev Ind Pharm 1995;21:1725-47.
Whitehead L, Fell JT, Collett JH, Sharma HL, Smith A. Floating dosage forms: an in vivo study demonstrating prolonged gastric retention. J Controlled Release 1998;55:3-12.
Oth M, Franz M, Timmermans J, Moes A. The bilayer floating capsule: a stomach-directed drug delivery system for misoprostol. Pharm Res 1992;9:298-302.
Etman E, Mahmoud EH, Galal S, Nada AH. Floating ranitidine micro particulates: development and in vitro evaluation. Int J Appl Pharm 2016;8:1-9.
Lee JH, Park TG, Choi HK. Development of oral drug delivery system using floating microspheres. J Microencapsul 1999;16:715-29.
Hwang SJ, Park H, Park K. Gastric retentive drug-delivery systems. Crit Rev Ther Drug Carrier Syst 1998;15:243-84.
Akiyama Y, Nagahara N, Kashihara T, Hirai S, Toguchi H. In vitro and in vivo evaluation of mucoadhesive microspheres prepared for gastrointestinal tract by polyglycerol ester of fatty acids and (acrylic acid) derivatives. Pharm Res 1995;12:397-405.
Groning R, Berntgen M, Georgarakis M. Acyclovir serum concentration following preoral administration of magnetic depot tablets and the influence of extracorporal magnets to control gastrointestinal transit. Eur J Pharm Biopharm 1998;46:285-91.
Fix JA, Cargill R, Engle K. Controlled gastric emptying. III. The gastric residence time of non-disintegrating geometric shapes in human volunteers. Pharm Res 1993;10:1087-9.
Kamath S, Kumar S. Design and evaluation of floating microspheres of rabeprazole sodium. Int J Pharm Pharm Sci 2012;4:357-67.
Perumandla PK, Sree P. Formulation and in vitro evaluation of floating microspheres of dextromethorphan hydrobromide. Int J Pharm Pharm Sci 2014;6:206-10.
Jain SK, Awasthi AM, Jain NK, Agrawal GP. Calcium silicate based microspheres of repaglinide for gastro retentive floating drug delivery: Preparation and in vitro characterization. J Controlled Release 2005;107:300-9.
Davis SN, Graner DK. Insulin oral hypoglycemic agents and the pharmacology of the pancreas in Godman and Gilmanâ€™s: the pharmacological basis of therapeutics. 10th ed. USA: McGraw-Hill Medical Publishing Division; 2001. p. 1704â€“5.
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.
Sharma M, Kohli S, Dinda A. In vitro and in vivo evaluation of repaglinide loaded floating microspheres prepared from different viscosity grades of HPMC polymer. Saudi Pharm J 2015;23:675-82.
Fu X, Ping Q, Gao Y. Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres. J Microencapsul 2005;22:57-66.
Srivastava AK, Ridhurkar DN, Wadhwa S. Floating microspheres of cimetidine: formulation, characterization and in vitro evaluation. Acta Pharm 2005;55:277-85.
Patel A, Ray S, Thakur RS. In vitro evaluation and optimisation of controlled release floating drug delivery System of metformin hydrochloride. Daru 2006;14:57-64.
Agbaje EO, Adeneye AA, Daramola AO. Biochemical and toxicological studies of aqueous extract of syzigiumaromaticum (L.) merr. andperry (myrtaceae) in the rodent. Afr J Tradit Complementary Altern Med 2009;6:241-54.
Maedler K, Carr RD, Bosco D, Zuellig RA, Berney T, Donath MY. Sulfonylurea-induced beta-cell apoptosis in cultured human islets. J Clin Endocrinol Metab 2005;90:501-6.