The purpose of the present study was to compare the in vitro release and to find out whether the bioavailability of a 75？mg indomethacin capsule (Microcid SR) was equivalent to optimized formulation (indomethacin-loaded cetyl alcohol microspheres). Indomethacin-loaded cetyl alcohol microspheres were prepared by meltable emulsified cooling-induced technique. Surface morphology of microspheres has been evaluated using scanning electron microscopy. A single dose, randomized, complete cross over study of IM microspheres was carried out on 10 healthy male and female Albino sheep’s under fasting conditions. The plasma was separated and the concentrations of the drug were determined by HPLC-UV method. Plasma indomethacin concentrations and other pharmacokinetic parameters obtained were statistically analyzed. The SEM images revealed the spherical shape of fat microspheres, and more than 98.0% of the isolated microspheres were in the size range 12–32？μm. DSC, FTIR spectroscopy and stability studies indicated that the drug after encapsulation with fat microspheres was stable and compatible. Both formulations were found to be bioequivalent as evidenced by in vivo studies. Based on this study, it can be concluded that cetyl alcohol microspheres and Microcid SR capsule are bioequivalent in terms of the rate and extent of absorption. 1. Introduction In recent years, various uses of wax and fat microspheres in the pharmaceutical field have come into forefront, involving the microspheres technology [1]. The goal of any drug delivery system is to provide a therapeutic amount of drug(s) to the proper site in the body in order to promptly achieve and thereby to maintain the desired drug concentrations during treatment. This idealized objective can be achieved by targeting the drugs to a specific organ or tissue with the help of controlling the release rate of the drug during the transit time in gastrointestinal tract. Poorly water-soluble drugs, which are lipophilic in nature mix, easily with fat and show good absorption rate. Among the reported conventional methods different strategies have been developed in recent years to design different types of wax microspheres loaded with hydrophilic and lipophilic drugs using toxic solvents. The use of such solvents during formulation is of environmental concern and also faces challenge to human safety. To overcome these problems, in the present investigation, water is used to prepare wax microspheres by meltable dispersed emulsified cooling-induced solidification method. Furthermore, the process was optimized to produce
References
[1]
L. Brannon-Peppas, “Recent advances on the use of biodegradable microparticles and nanoparticles in controlled drug delivery,” International Journal of Pharmaceutics, vol. 116, no. 1, pp. 1–9, 1995.
[2]
E. Karasulu, H. Ye？im Karasulu, G. Ertan, L. Kirilmaz, and T. Güneri, “Extended release lipophilic indomethacin microspheres: formulation factors and mathematical equations fitted drug release rates,” European Journal of Pharmaceutical Sciences, vol. 19, no. 2-3, pp. 99–104, 2003.
[3]
R. C. Rowe, P. J. Sheskey, and M. Quinn, Handbook of Pharmaceutical Excipients, Pharmaceutical Press, London, UK, 5th edition, 2005.
[4]
M. Brien, J. McCauley, and E. Cohen, “Indomethacin,” in Analytical Profiles of Drug Substances, K. Florey, Ed., pp. 211–238, Academic Press, London, UK, 2005.
[5]
M. Bogdan, A. Pirnau, C. Floare, and C. Bugeac, “Binding interaction of indomethacin with human serum albumin,” Journal of Pharmaceutical and Biomedical Analysis, vol. 47, no. 4-5, pp. 981–984, 2008.
[6]
M. Amir and S. Kumar, “Anti-inflammatory and gastro sparing activity of some new indomethacin derivatives,” Archiv der Pharmazie, vol. 338, no. 1, pp. 24–31, 2005.
[7]
S. Tamilvanan and B. Sa, “Studies on in vitro release behaviour of indomethacin-loaded polystyrene microparticles,” International Journal of Pharmaceutics, vol. 201, no. 2, pp. 187–197, 2000.
[8]
D. B. Myers, K. Wilson, and D. G. Palmer, “An objective measurement of change in morning stiffness,” Rheumatology International, vol. 1, no. 3, pp. 135–137, 1981.
[9]
S. Salib, S. Donney, and D. Doyle, “Therapy and drugs in the control of osteo arthritis,” Prescr, vol. 8, pp. 41–59, 1996.
[10]
D. V. Gowda and H. G. Shivakumar, “Encapsulation of theophylline into waxes /fat microspheres, preparation, characterization & release kinetics,” Hamdard Medicus, vol. 50, pp. 69–81, 2007.
[11]
L. I. Giannola, V. De Caro, and A. Severino, “Carnauba wax microspheres loaded with valproic acid: preparation and evaluation of drug release,” Drug Development and Industrial Pharmacy, vol. 21, no. 13, pp. 1563–1572, 1995.
[12]
D. V. Gowda and H. G. Shivakumar, “Encapsulation of griseofulvin in waxes/ fat microspheres: preparation, characterization and release kinetics of microspheres,” Indian Drugs, vol. 42, no. 7, pp. 453–460, 2005.
[13]
E. J. Parish, T. L. Boos, and S. Li, “The chemistry of waxes and sterols,” in Food Lipids: Chemistry, Nutrition, and Biochemistry, C. C. Akoh and D. B. Min, Eds., Marcel Dekker, New York, NY, USA, 2nd edition, 2002.
[14]
D. V. Gowda and H. G. Shivakumar, “Comparative bioavailability studies of indomethacin from two-controlled release formulations in healthy albino sheep,” Indian Journal of Pharmaceutical Sciences, vol. 68, no. 6, pp. 760–763, 2006.
[15]
D. V. Gowda, B. Girish, H. G. Shivakumar, and A. Moin, “Preparation and evaluation of carnauba wax microspheres loaded with aceclofenac for controlled release,” Indian Journal of Pharmaceutical Education and Research, vol. 42, no. 4, pp. 329–336, 2008.
[16]
United State Pharmacopoeia 24/National formulary 19, United State Pharmacopoeial Convention, Rockville, Md, USA, 1999.
[17]
A. G. Johnson and J. E. Roy, “Improved HPLC method for the determination of indomethacin in plasma,” Therapeutic Drug Monitoring, vol. 14, pp. 61–65, 1992.
[18]
E. Pascual and F. Sivera, “Therapeutic advances in gout,” Current Opinion in Rheumatology, vol. 19, no. 2, pp. 122–127, 2007.
[19]
Food and Drug administration, Division of biopharmaceutics, Bioavailability and NDA submission regulations, 1977.
[20]
FDA Guidelines for Industry, “Extended release oral dosage form evaluation and application for in vitro- in vivo correlation,” Dissolution Technologies, vol. 4, pp. 23–31, 1997.
