Preparation and evaluation of oral controlled release mucoadhesive Microspheres of Ketorolac Tromethamine

Potu Appa Rao Rao, Prabhakar Reddy Veera Reddy


Recently, lot of emphasis is being laid on oral controlled release multiple unit particulate (MUP) dosage forms, for their significant and potential benefits.  Ketorolac tromethamine (KTM) is a potent non-narcotic analgesic and anti-inflamatory drug administered orally in multiple divided doses (10 mg four times a day) for the management of mild to moderate post-operative pain. KTM’s short biological half-life demands frequent administration of the drug leading to poor patient compliance and inadequate pain management. Hence, the present investigation was undertaken to develop and evaluate oral controlled release mucoadhesive microspheres by ionotropic gelation method using natural and biodegradable polymers such as sodium carboxy methyl cellulose (Na CMC) and sodium alginate (SA). The influence of various formulation factors on the drug entrapment  efficiency,  in vitro drug release, micromeritic properties, and  mucoadhesion ability  was investigated. Scanning electron micrographs of alginate beads loaded with drug exhibited rough surface morphology and  sizes were found to be  in the range of 842 to 1265 µm. Among all the formulations, the drug loaded microspheres of formulation CA6   showed the highest drug release retarding effect over a period of  8  hours.  The drug-polymer compatibility studies and solid state properties were investigated by Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC) X- Ray diffraction techniques (X-RD).


Microspheres, Ketorolac tromethamine, controlled release, Ionotropic gelation technique, FTIR

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. Fallingborg J, Christensen LA, Jacobson BA, Rasmussen SN. Very low intraluminal colonic pH in patients with active ulcerative colitis. Dig Dis Sci 1993;38:89-93.

. Shaji J., Chadawar V.,Talwalkar P., Multiparticulate Drug Delivery System, The Indian Pharmacist, June 2007, 6(60): 21-28.

. Kramer A, Turk S, Vrecer F. Statistical optimization of diclofenac sodium sustained release pellets coated with polymethacrylic films. Int J Pharm 2003;256:43-52.

.Davis SS. Assessment of gastrointestinal transit and drug absorption. Novel drug delivery and its therapeutic application. Wiley Cichester; 1989. p. 89-101.

. Tang E. S.K., Chan L.W, Heng P.W.S, Coating of Multiparticulates for Sustained Release, Amer JDrug Delivery 2005: 3(1): 17-28.

. Laila F. A.A., Chandran S., Multiparticulate Formulation approach to colon specific drug delivery current perspectives, J. Pharm Pharm Sci, 2006, 9(3): 327-338.

. Coviello T., Grassi M., Palleschi A., Bocchinfuso G., Coluzzi G., Banishoeib F. and Alhaique, F. A new scleroglucan/borax hydrogel: swelling and drug release studies. Int J Pharm. 2005; 289: 97-107.

. Takka S, Acarturk F. 1999b. Calcium alginate microparticles for oral administration. I: Effect of sodium alginate type on drug release and drug entrapment efficiency. Journal of Microencapsulation 16:275–290.

. Jain A., Gupta Y. and Jain S. K. Perspectives of biodegradable natural polysaccharides for site-specific drug delivery to the colon. J Pharm Pharm Sci. 2007; 10: 86-128.4.

. Zhang, L. (2001), J. Appl. Polym. Sci., 82, 584-592.

. Koh, G. L., Tucker, J. G. (1988), J. Pharm. Pharmacol., 40, 309-312.

. Chandermun K, Danprox CM, Govender T. The effect of selected formulation and process variables on the release characteristics of pellets produced by extrusion - spheronisation. Proc Int Symp Control Rel Bioact Mater 1998;25:942-3.

. Buckley M.M.T., Brogden R.N. - Ketorolac: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. - Drugs, 39, 86-109, 1990.

. Shyamala B, Sanmathi BS. Poly(lactic acid) microspheres of Ketorolac tromethamine for parenteral controlled drug delivery system. Indian J Pharm Sci. 2001;63:538–540.

. Tiwari S.B., Udupa N. - Investigation into the potential of iontophoresis facilitated delivery of ketorolac. - Int. J. Pharm., 2003, 260, 93-103.

. Jalonde EG, Blanco-Prieto MJ, Ygartua P, Santoyo S, Increasedefficacy of acyclovirloaded microparticles against herpes simplex virus type 1 in cell culture. Eur. J. Pharm. Biopharm, 2003;56:183-187.

. Grabovac V, Guggi D, Schnurch AB, Comparison of the mucoadhesive properties of various polymers, Adv. Drug Del. Rev, 2005;57:1713-1723.

. G.Fandueanu, M. Constantin, A. Dalpiaz, F.Borolotti,, R. Cortesi, P.Ascenzi (2004). Preparation and characterization of starch/ cyclodextrin bioadhesive microspheres as platform for nasal administration of Gabexate Mesylate in allergic rhinitis treatment. Biomaterial 25, 59-70.

. Asane GS, Nirmal SA, Rasal KB, Naik AA, and Mahadik MS, Polymers for Mucoadhesive Drug Delivery System: A Current Status.Informa health care, 2008;34:1246-1266.Asane et al., 2011.

. Rodriguez M., Vila-Jato J. L. and Torres D. Design of a new multiparticulate system for potential site-specific and controlled drug delivery to the colonic region. J Control Release. 1998; 55: 67-77.

. Prajapati SK, Tripathi P, Ubaidulla U, Anand V (2008) Design and development of gliclazide mucoadhesive microcapsules: in vitro and in vivo evaluation. AAPS PharmSciTech 9, 224–30.

. R.A. Fursule, CH. N. Patra, G.B.Patil, S.B.Kosalge, International Journal of ChemTech Research, 2009; 1(2), 162-167.

. Kawashima Y, Niwa T, Takeuchi H, Hino T, Itoh Y. J Pharm Sci 1992; 81:135-140

. Lee BJ, Cui JH, Kim TW, Heo MY, Kim CK. 1998. Biphasic release characteristics of dual drug-loaded alginate beads. Archives of Pharmaceutical Research 21:645–650.

. Kawashima Y, Niwa T, Handa T, Takeuchi H, Iwamoto T, Itoh K. 1989. Preparation of controlled-release microspheres of ibuprofen with acrylic polymers by a novel quasi-emulsion solvent diffusion method. Journal of Pharmaceutical Science 78:68–72.


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