DEVELOPMENT OF MUCOADHESIVE CARBOHYDRATE HETEROPOLYMER MICROBEADS FOR SUSTAIN RELEASE OF THEOPHYLLINE
Keywords:Mucoadhesive, Natural polymers, Microbeads, Sustained release, Theophylline
Objective: The aim of present study was to develop and evaluate mucoadhesive microbeads for oral sustained release of an antiasthmatic agent theophyllineâ€ using natural gums such as sodium alginate and sesbania gum.
Methods: The compatibility studies of drug with different polymers were investigated by using DSC (Differential Scanning Calorimeter) and FTIR (Fourier Transform Infrared Spectroscopy). Carbohydrate heteropolymer microbeads of alginate and sesbania gums were prepared by ionotropic gelation technique, where calcium chloride is used as a source of counter ions. Prepared beads were characterized for particle size, entrapment efficiency, surface morphology, swelling index, in vitro release studies and release kinetics.
Results: Final optimized formulation consists of a polymer blend of alginate and sesbania gum with hydroxy propyl cellulose as release modifier. Microbeads exhibited good swelling index and high percentage of drug entrapment efficiency. The developed formulation showed a maximum drug release of 92% in 11 h using 0.1 N hydrochloric acid buffer (pH 1.2). The formulation followed Korsmeyer-Peppas and Higuchi release mechanism, releasing the drug by non-fickian diffusion. Prepared beads showed significant mucoadhesion in acidic buffer.
Conclusion: The sustained release microbeads were successfully designed for oral administration of theophylline which may be used for the treatment of nocturnal asthma.
Rao A, Shivalingam MR, Reddy YV, Sunitha N, Jyothibasu T, Shyam T. Design and evaluation of sustained release microcapsules containing diclofenac sodium. Int J Pharm Biomed Res 2010;1:90-3.
Mangond BS, Sreedhar V, Baraskar W, Kulkarni RV. Development and evaluation of gellan gum based hydrogel microbeads for controlled release of ketoprofen. Indian J Novel Drug Delivery 2009;1:32-5.
Mathur V, Mathur NK. Fenugreek and other lesser known galactomannan polysaccharides-Scope for development. J Sci Ind Res 2005;64:475-81.
Weinberger M, Hendeles L. Slow-release theophylline: rationale and basis for product selection. N Engl J Med 1983;8:760-4.
Tandon MK, Kailis SG. Bronchodilator treatment for partially reversible chronic obstructive airways disease. Thorax 1991;46:248-51.
Garg R, Gupta GD. Progress in controlled gastro retentive delivery systems. Trop J Pharm Res 2008;7:1055-66.
Forizs E, Patrut A, Cozar IB, David L. Synthesis, structure elucidation of palladium complexes with theophylline. Academia Romana Roum Chim 2010;55:697-704.
Bhagwat DA, Bhutkar MA, Todkar SS, Mohite SK, Gattani YS. Formulation and evaluation of controlled release microspheres of isosorbide dinitrite. Int J Pharm Technol Res 2009;1:125-8.
Wan Ngah WS, Fatinathan S. Adsorption of Cu2+ions in aqueous solution using chitosan beads, chitosan-GLA beads and chitosan alginate beads. Chem Eng J 2008;143:62-72.
Iglesias B, Coronilla R, Concheiro A, Lorenzo C. Preparation of chitosan beads by simultaneous cross linking/insolubilisation in basic pH/Rheological optimization and drug loading/release behavior. Eur J Pharm Sci 2005;24:77-84.
Maiti SB, Somdipta R, Ray SM. Al+3 ion cross-linked and acetylated gellan hydrogel network beads for prolonged release of glipizide. Carbohydr Polym 2011;85:164-72.
Jagtap YM, Bhujpal RK, Ranade AN, Ranpise RS. Effect of various polymer concentrations on physicochemical properties of floating microspheres. Indian J Pharm Sci 2012;74:512-20.
Lachman L, Lieberman HA, Kanig JL. The theory and practice of industrial pharmacy. 3rd ed. Mumbai: Varghese Publishing House; 1987.
Sinko PJ. editor. Martin's physical pharmacy and pharmaceutical science. 5th ed. Baltimore: Lippincott Williams and Wilkins; 2006.
Larson I, Dass CR, Choong PF, Dunstan DE. A chitosan-dipotassium orthophosphate hydrogel for the delivery of doxorubicin in the treatment of osteosarcoma. Biomaterials 2009;2:213-20.
Nayak AK, Hasnain MS, Beg S, Alam M. Mucoadhesive beads of gliclazide: Design, development and evaluation. Sci Asia 2010;36:319-25.
Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 1983;15:25-35.