Abstract
Purpose
The purpose of present study is to formulate microemulsion composed of oleic acid, phosphate buffer, Tween 80, ethanol and to investigate its potential as drug delivery system for an antitubercular drug isoniazid.
Materials and Methods
The pseudo-ternary phase diagram (Gibbs Triangle) was delineated at constant surfactant/co-surfactant ratio (Km 0.55). Changes in the microstructure were established using conductivity (σ), viscosity (η), surface tension (γ) and density measurements. Dissolution studies and particle size analysis were carried out to understand the release of isoniazid from the microemulsion formulation. Further, partitioning studies and spectroscopic analysis (FT-IR and 1H NMR) was performed to evaluate the location of drug in the colloidal formulation.
Results
Physico-chemical analysis of microemulsion system showed the occurrence of structural changes from water-in-oil to oil-in-water microemulsion. It has been observed that the microemulsion remained stable after the incorporation of isoniazid (in terms of optical texture, pH and phase separation). The changes in the microstructure of the microemulsion after incorporation of drug was analyzed on the basis of partition studies of isoniazid in microemulsion components and various parameters viz pH, σ, η,γ. In addition, the particle size analysis indicates that the microemulsion changes into o/w emulsion at infinite dilution. The spectroscopic studies revealed that most of the drug molecules are present in the continuum region of an o/w microemulsion. Dissolution studies infer that a controlled release of drug is expected from o/w emulsion droplet. In the present system the release of isoniazid from microemulsion was found to be non-Fickian.
Conclusion
The present Tween based microemulsion appears beneficial for the delivery of the isoniazid in terms of easy preparation, stability, low cost, sustained and controlled release of a highly water soluble drug.
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References
W. A. Ristsehel. Microemulsions for improved peptide absorption from the gastrointestinal tract. Method find. Exp. Clin. 13:205–220 (1991).
J. M. Sareiaux, L. Acar, and P. A. Sado. Using microemulsion formulations for oral delivery of therapeutic peptides. Int. J. Pharm. 120:127–136 (1995).
P. P. Constantinides. Lipid microemulsion for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharm. Res. 12:1561–1572 (1995).
T. R. Kummaro, B. Gurley, M. A. Khan, and I. K. Reddy. Self-emulsifying drug delivery systems (SEMDDS) of co-enzyme Q10: formulation development and bioavailablity assessment. Int. J. Pharm. 212:233–246 (2001).
C. K. Kim, Y. J. Cho, and Z. J. Gao. Preparation and evaluation of biphenyl dimetyl dicarboxylate microemulsons for oral delivery. J. Control. Release 70:149–155 (2001).
K. Kawakami, T. Yoshikawa, T. Hayashi, Y. Nishihara, and K. Masuda. Microemulsion formulation for enhanced absorption of poorly soluble drugs II. In vivo study. J. Control. Release 81:75–82 (2002).
C. W. Pouton. Formulation of self-emulsifying drug delivery systems. Adv. Drug Deliv. Rev. 25:47–58 (1997).
H. N. Bhargava, A. Narurkar, and I. M. Lieb. Using microemulsion for drug delivery. Pharm. Technology 1:46–54 (1987)
M. Trotta, S. Morel, and M. R. Gasco. Effect of oil phase composition on the skin permeation of felodipine from o/w microemulsion. Pharmazie 52:50–53 (1997).
M. A. Bolzinger, T. C. Carduner, and M. C. Poelman. Bicontinuous sucrose ester microemulsion: a new vehicle for tropical delivery of niflumic acid. Int. J. Pharm. 176:39–45 (1998).
M. Kreigaard, M. J. Kemme, J. Burggraaf, R. C. Schoemaker, and A. F. Cohen. Influence of microemulsion vehicle on a cutaneous bioequivalence of a lipophilic model drug assessed by microdialysis and pharmacodynamics. Pharm. Res. 18:593–599 (2001).
M. Kreigaard, E. J. Pederson, and J. W. Jaroszewski. NMR characterization and transdermal drug delivery potential of microemulsion system. J. Control. Release 69:421–433 (2000).
L. Lehmann, S. Keipert, and M. Gloor. Effects of microemulsions on the stratum corneum and hydrocortisone penetration. Eur. J.Pharm. Biopharm. 52:129–136 (2001).
K. Kriwet, and C. C. Muller-Goymann. Diclofenac release from phospholipid drug systems and permeation through excised human stratum corneum. Int. J. Pharm. 125:231–242 (1995).
M. Trotta. Infleunce of phase transformation on indomethacin release from microemulsions. J. Control. Release 60:399–405 (1999).
M. E. Dalmora, and A. G. Oliveria. Inclusion complex of peroxicam with β-cyclodextrin and incorporation in heaxdecyltrimethyl ammonium bromide based microemulsions. Int. J. Pharm. 184:157–164 (1999).
F. Pattarino, E. Marengo, and M. R. Gasco. Experimental design and partial least square in the study of complex mixtures: microemulsions as drug carriers. Int. J. Pharm. 91:157–165 (1993).
P. Kumar and K. L. Mital. Handbook of microemulsion: science and technology, Marcel Dekker, New York, 1999.
F. Podlogar, M. Gašperlin, M. Tomšič, A. Jamnik, and M. Bešter-Rogač. Structural characterization of water-Tween 40®–Imwitor 308®–isopropyl myristate using different experimental methods. Int. J. Pharm. 276;115–128 (2004).
A. Lopez, F. Linares, C. Cortell, and M. Herraez. Comparative enhancer effects of Span 20® with Tween 20® and Azone® on the in vitro percutaneous penetration of compounds with different lipophilicities. Int. J. Pharm. 202:133–140 (2000).
J.-Y. Fang, S.-Y. Yu, P.-C. Wu, Y.-B. Huang, and Y.-H. Tsai. In vitro skin permeation of estradiol from various proniosome formulations. Int. J. Pharm. 215:91–99 (2001).
A. H. Kibbe. Handbook of Pharmaceutical Excipients, 3rd ed. Pharmaceutical, London, 2000.
M. J. Lawerence and G. D. Rees. Microemulsion based media as novel drug delivery systems. Adv. Drug Deliv. Rev. 45:89–121 (2000).
J. Kreuter. Nanoparticles. In Colloidal Drug Delivery Systems, Marcel Dekker, New York (1994).
A. T. Florence and D. Attwood. Physicochemical Principles of Pharmacy, 3rd ed. Macmillan, London.
R. Guo, S. Qian, J. Zhu, J. Qian. The release of cephanone in CTAB/n-C5H11OH/H2O system. Colloid. Polym. Sci. 284:468–474 (2006).
L. C. du Toit, V. Pillay, and M. P. Danckwerts. Tuberculosis chemotherapy: current drug delivery approaches. Resp. Res. 7:118–136 (2006).
J. L. Lando and H. T. Oakley. Tabulated correction factors for the drop-weight-volume determination of surface and interracial tensions. J. Colloid Interface Sci. 25:526–528 (1967).
L. K. Pershing, G. E. Parry, and L. D Lambert. Disparity of in vitro and in vivo oleic acid-enhanced β-estradiol percutaneous absorption across human skin. Pharm. Res. 10:1745–1750 (1993).
H. Tanojo, H.E. Junginger, and H.E. Boddé. In vivo human skin permeability enhancement by oleic acid: transepidermal water loss and Fourier-transform infrared spectroscopy studies. J. Control. Release 47:31–39 (1997).
S. Peltola, P. J. Saarinen-Savolainen, T. M. Suhonen, and A. Urtti. Microemulsions for topical delivery of estradiol. Int. J. Pharm. 254:99–107 (2003).
N. Subramanium, S. Ray, S. K. Ghosal, R. Bhadra, and S. P. Moulik. Formulation design of self-microemulsifying drug delivery systems for improved oral bioavailability of celecoxib. Biol. Pharm. Bull. 27:1993–1999 (2004).
F. F. Lv, L.Q. Zheng, and C.-H. Tung. Phase behavior of the microemulsions and the stability of the chloramphenicol in the microemulsion-based ocular drug delivery system. Int. J. Pharm. 301:237–246 (2005).
K. V. Schubert and E. W. Kaler. Nonionic microemulsions. Phys. Chem. 100:190–205 (1996).
R. G. Alany, T. Rades, S. Agatonovic-Kustrin, N. M. Davies, and I. G. Tucker. Effects of alcohols and diols on the phase behavior of quaternary systems. Int. J. Pharm. 196:141–145 (2000).
S. K. Mehta and K. Bala. Tween based microemulsions: a percolation view. Fluid Phase Equilibra 172:197–209 (2000).
G. S. Grest, I. Webman, and S. A. Safran. Dynamic percolation in microemulsions. Phys. Rev. A 33(4):2842–2845 (1986).
B. Lagourette, J. Peyrelasse, C. Boned, and M. Clausse. Percolative conduction in microemulsion type systems. Nature 281:60–62 (1979).
S. K. Mehta and K. Bala. Volumetric and transport properties in microemulsions and the point of view of percolation theory. Phys. Rev. E. 51:5732–5737 (1995).
K. E. Bennett, J. C. Hatfield, H. T. Davis, C. W. Macosko, and L. E. Seriven. Viscosity and conductivity of microemulsions. In: Robb, I. D. (ed.), Microemulsions, Plenum, New York, pp 65–84 (1982).
R. K. Mitra and B. K. Paul. Physicochemical investigations of microemulsification of eucalyptus oil and water using mixed surfactants (AOT + Brij35) and butanol. J. Colloid Inter. Sci. 283:565–577 (2005)
M. E. Leser, W. C. Evert, and W. G. M. Agterof. Phase behaviourof lecithin–water–alcohol–triacylglycerol mixtures. Colloids Surf. A., 116:293–308 (1996).
F. Aliotta, P. Migliardo, D. I. Donato, V. Turco Liveri, E. Bardez, and B. Larry. Local hydration effects in reversed micellar aggregation. Progr. Colloid Polym. Sci. 89:258–262 (1992).
V. Arcoleo, M. Goffredi, V. Turco Liveri. Physicochemical characterization of copper (II) bis(2-ethylhexyl) sulfosuccinate reversed micelles. J. Colloid Int. Sci. 198:216–223 (1998).
H. M. El-Laithy. Preparation and physicochemical characterization of dioctyl sodium dulfosuccinate (Aersol OT) microemulsion for oral drug delivery. AAPS PharmSciTech 4(Article 11):1–10 (2003).
H. Dai, Q. Chen, H. Qin, Y. Guan, D. Shen, Y. Hua,Y. Tang, and J. Xu. A temperature-responsive copolymer hydrogel in controlled drug delivery. Macromolecules 39:6584–6589 (2006)
N. Wakiyama, K. Juni, and M. Nakano. Preparation and evaluation in vitro of polylactic acid microspheres containing local anesthetics. Chem. Pharm. Bull. 29:3363–3368 (1981).
L. Zhang, X. Sun, and Z.-R. Zhang. An investigation on liver-targeting microemulsions of norcantharidin. Drug Deliv. 12:289–295 (2005).
C. Washington. Drug release from microdisperse systems: a critical review. Int. J. Pharm. 58:1–12 (1990).
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S.K.M. is thankful to UGC and DST India for financial assistance.
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Mehta, S.K., Kaur, G. & Bhasin, K.K. Incorporation of Antitubercular Drug Isoniazid in Pharmaceutically Accepted Microemulsion: Effect on Microstructure and Physical Parameters. Pharm Res 25, 227–236 (2008). https://doi.org/10.1007/s11095-007-9355-8
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DOI: https://doi.org/10.1007/s11095-007-9355-8