ENHANCEMENT OF DISSOLUTION RATE OF MODAFINIL USING SOLID DISPERSIONS WITH POLYETHYLENEGLYCOLS
Abstract
Solid dispersions (SDs) of modafinil (MDF) were prepared using polyethyleneglycols (PEGs), in 1;1, 1;2 and 1;4 proportions by fusion, solvent evaporation and physical mixing method. Differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD) were used to examine the physical state of the drug. The data from the XRD showed that the drug was converted to amorphous form as the number and intensity of peaks were decreased in solid dispersion as compared to pure drug and physical mixture of drug and carrier. DSC thermograms also confirmed the change in physical state of the drug as the peaks were altered or disappeared. With the highest ratio of the carriers (1:4), the drug solubility was enhanced by 38.68, 34.78 and 9.29 folds in solvent evaporation, fusion and physical mixing methods respectively. Solid dispersion batch S6 containing drug:PEG6000 in 1:4, was selected to be formulated as tablet (batch TS6) and evaluated for in vitro drug dissolution & six month stability. An increased dissolution rate of modafinil was observed from SDs and PMs, as compared to pure crystalline drug. The dissolution rate of modafinil from its PMs or SDs increased with an increasing amount of polymer.
Key words: Fusion, solvent evaporation, physical mixture, in vitro dissolution, characterization.
Full Text:
UntitledReferences
Ahuja, B. C., Katare, O. P. and Singh, B., 2007, Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers, Eur. J. Pharm. Biopharm., 65, 26-38.
Ambike, A. A., Mahadik, K. T. and Paradkar, A., 2005, Spray-dried amorphous solid dispersions of simvastatin, a low Tg drug: in vitro and in vivo evaluations, Pharm. Res.,22, 990-998.
Chiou, W. L. and Riegelman, S., 1971, Pharmaceutical applications of solid dispersion systems, J. Pharm. Sci., 60, 1281-1302.
Chiou, W. L., and Riegelman, S., 1969, Preparation and dissolution characteristics of several fast-release solid dispersions of griseofulvin, J. Pharm. Sci.,60, 1281-1302.
Craig, D. Q. M., 2002, The mechanism of drug release from solid dispersions in water soluble polymers, Int. J. Pharm., 231, 131-144.
Ford, J. L., 1986, The current status of solid dispersions. Pharm. Acta Helv., 61 69-88.
Hajratwala, B. R., 1974, Dissolution of solid dispersion systems, Aust. J. Pharm. Sci., NS3, 101-109.
Hancock, B. C., 2002, Disordered drug delivery: destiny, dynamics and the Deborah number, J. Pharm. Pharmacol.,54, 737-746.
Jacobs, M. J., McIntyre, B. T., Parikh, A. and Patel, P. R., 2002, Pharmaceutical solutions of modafinil compounds, U.S. Pat. 6,919,378.
Khawam, A. and Flanagan, D., 2006, Solidstate kinetic model: basics and mathematical fundamentals, J. Phys. Chem. B., 110, 17315-17328.
Leuner, C., and Dressman, J., 2000, Improving drug solubility for oral delivery using solid dispersions, Eur. J. Pharm. Biopharm., 50, 47-60.
Marsac, P. J., Konno, H. and Taylor, L. S., 2006a, A comparison of the physical stability of amorphous felodipine and nifedipine systems, Pharm. Res., 23, 2306-2315.
Marsac, P. J., Shamblin, S. L. and Taylor, L. S., 2006b, Theoretical and practical approaches for prediction of drug–polymer miscibility and solubility, Pharm. Res., 23, 2417-2426.
Mayersohn, M. and Gibaldi, M., 1966, New method of solid state dispersion for increasing dissolution rates, J. Pharm. Sci., 55, 1323-1324.
Minzenberg, M. J. and Carter, C. S., 2007, Modafinil: A Review of Neurochemical Actions and Effects on Cognition, Neuropsychopharmacology, 33, 1-26.
Vippagunta, S. R., Wang, Z., Hornung, S. and Krill, S., 2007, Factors affecting the formation of eutectic solid dispersions and their dissolution behavior, J. Pharm. Sci., 96, 294-304.
DOI: http://dx.doi.org/10.14499/indonesianjpharm23iss4pp209-215
Refbacks
- There are currently no refbacks.
Copyright (c) 2017 INDONESIAN JOURNAL OF PHARMACY
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Indonesian J Pharm indexed by:
View My Stats