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AAPS PharmSciTech. 2007 March; 8(1): E100–E108.
Published online 2007 February 23. doi:  10.1208/pt0801014
PMCID: PMC2750449

Formulation and evaluation of ketorolac tromethamine-loaded albumin microspheres for potential intramuscular administration


The objective of this work was to prepare and evaluate ketorolac tromethamine-loaded albumin microspheres using a factorial design. Albumin microspheres were prepared by emulsion cross-linking method. Selected formulations were characterized for their entrapment efficiency, particle size, surface morphology, and release behavior. Analysis of variance (ANOVA) for entrapment efficiency indicated that entrapment efficiency is best fitted to a response surface linear model. From the statistical analysis it was observed that as the drug:polymer (D[ratio]P) ratio and volume of glutaraldehyde increased, there was a significant increase in the encapsulation efficiency. Scanning electron microscopy of the microspheres revealed a spherical, nonporous and uniform appearance, with a smooth surface. Based on the entrapment efficiency and physical appearance, 9 formulations were selected for release study. The maximum particle size observed was below 40 μm. The release pattern was biphasic, characterized by an initial burst effect followed by a slow release. All selected microspheres, except those having less polymer proportion (D[ratio]P ratio is 1[ratio]1), exhibited a prolonged release for almost 24 hours. On comparingr2 values for Higuchi and Peppas kinetic models, different batches of microspheres showed Fickian, non-Fickian, and diffusion kinetics. The release mechanism was regulated by D[ratio]P ratio and amount of cross-linking agent. From the experimental data obtained with respect to particle size and extent of drug relaase, it could be concluded that the prepared microspheres are useful for once-a-day intramuscular administration of ketorolac tromethamine.

Keywords: Ketorolac tromethamine, albumin microspheres, intramuscular administration, Higuchi and Peppas kinetic models

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Selected References

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1. Bartfield JM, Kern AM, Robak RN, Snyder HS, Baevsky RH. Ketorolac tromethamine use in a university-based emergency department. Acad Emerg Med. 1994;1:532–538. doi: 10.1111/j.1553-2712.1994.tb02548.x. [PubMed] [Cross Ref]
2. Gupta AK, Madan S, Majumdar DK, Maitra A. Ketorolac entrapped in polymeric micelles: preparation, characterisation and ocular anti-inflammatory studies. Int J Pharm. 2000;209:1–14. doi: 10.1016/S0378-5173(00)00508-1. [PubMed] [Cross Ref]
3. Sjoergen J. Rate Control in Drug Therapy. Edinburgh, UK: Churchill Livingstone; 1985.
4. Gupta PK, Hung CT. Albumin microspheres. 1. Physico-chemical characteristics. J Microencapsul. 1989;4:427–462. doi: 10.3109/02652048909031165. [PubMed] [Cross Ref]
5. Bahukudumbi P, Carson KH, Rice-Ficht AC, Andrews MJ. On the diameter and size distributions of bovine serum albumin (BSA)-based microspheres. J Microencapsul. 2004;21:787–803. doi: 10.1080/02652040400015395. [PubMed] [Cross Ref]
6. Bernard NG, Shaw SM, Kessler WV, Landolt RR, Peck GE, Dockerty GH. Distribution and degradation of iodine-125 albumin microspheres and technetium-99m sulphur colloid. Can J Pharm Sci. 1980;15:30–34.
7. Zolle I, Rhodes BA, Wagner HN. Preparation of metabolizable radioactive human serum albumin microspheres for studies of the circulation. Int J Appl Radiat Isot. 1970;21:155–167. doi: 10.1016/0020-708X(70)90006-2. [PubMed] [Cross Ref]
8. Abdullah ME, Al-Khamis KI. Microcomputer program for the assessment of one-way, two-way and factorial analysis of variance in pharmaceutical data. Comput Methods Programs Biomed. 1993;41:131–133. doi: 10.1016/0169-2607(93)90072-S. [PubMed] [Cross Ref]
9. Chuo WH, Tsai TR, Hsu SH, Chain TM. Development of nifedipine-loaded albumin microspheres using a statistical factorial design. Int J Pharm. 2007;134:247–251. doi: 10.1016/0378-5173(95)04429-9. [Cross Ref]
10. Kumar V, Lewis SA, Mutalik S, Shenoy DB, Udupa N. Biodegradable microspheres of curcumin for treatment of inflammation. Indian J Physiol Pharmacol. 2002;46:209–217. [PubMed]
11. Zahirul M, Khan I. Dissolution testing for sustained or controlled release oral dosage forms and correlation with in vivo data: challenges and opportunities. Int J Pharm. 2007;140:131–143. doi: 10.1016/0378-5173(96)04561-9. [Cross Ref]
12. Higuchi T. Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci. 1961;50:874–875. doi: 10.1002/jps.2600501018. [PubMed] [Cross Ref]
13. Korsmeyer RW, Gurny R, Doelker EM, Buri P, Peppas NA. Mechanism of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15:25–35. doi: 10.1016/0378-5173(83)90064-9. [Cross Ref]
14. Peppas NA. Analysis of Fickian and non-Fickian drug release from polymers. Pharm Acta Helv. 1985;60:110–111. [PubMed]
15. Sahin S, Selek H, Ponchel G, et al. Preparation, characterization and in vivo distribution of terbutaline sulfate loaded albumin microspheres. J Control Release. 2002;82:345–358. doi: 10.1016/S0168-3659(02)00141-4. [PubMed] [Cross Ref]
16. Armstrong AN, James KC. Pharmaceutical Experimental Design and Interpretation. Bristol, PA: Taylor and Francis; 2007.
17. Mendenhall W, Sincich T. A Second Course in Business Statistics: Regression Analysis. San Francisco, CA: Dellen Publishing; 1989. pp. 141–226.
18. Morimoto K, Katsumata H, Yabuta T, et al. Evaluation of gelatin microspheres for nasal and intramuscular administrations of salmon calcitonin. Eur J Pharm Sci. 2001;13:179–185. doi: 10.1016/S0928-0987(01)00094-X. [PubMed] [Cross Ref]

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