Sustained Release Solid Dispersions of Pentoxyfylline: Formulation and Optimization
Keywords:Solid dispersion, eudragits, solubility studies, dissolution, scanning electron microscopy
Objective: The purpose of the study is to formulate and optimize sustained release solid dispersions of pentoxyfylline using a combination of eudragit polymers and ethyl cellulose. Methods: Solid dispersions were formulated by solvent evaporation method.Preliminary batches were formulated using various drug to polymer ratio; with eudragit S100 and L100 (1:1 to 1:5 ratio), and with ethyl cellulose(1:1 to 1:3 ratio) and evaluated for solubility analysis. Based on results of preliminary batches, Box Behnken design was further applied and three factors (X1- concentration of Eudragit S100, X2- concentration of Eudragit L100, X3- concentration of Ethyl Cellulose) were selected with three levels (+1, 0, -1). Multiple linear regression was applied to generate polynomial equations and statistical evaluation. Prepared solid dispersions were investigated for sustained release properties via in vitro dissolution studies. Fourier transform infrared spectroscopic analysis (FTIR), X-ray diffraction analysis (X-RD), Differential scanning calorimetry (DSC) studies were carried out to evaluate drug polymer interactions. Scanning Electron Microscopy (SEM) analysis of optimized solid dispersion was carried out to evaluate surface morphology of the particles. Results: Batch F5 showed maximum sustained release (65.46% in 24 h) characteristics out of all solid dispersions. DSC studies indicated drug integrity when mixed with the polymeric carriers. FTIR and X-RD studies also ruled out any drug polymer interaction. A change in crystalline habit was observed in solid dispersion particles (F5 batch) as seen in SEM micrographs. Polynomial mathematical model generated using multiple regression analysis was found to be statistically significant (p<0.05). Conclusion: Release retarding effect was found to be dependent on polymer concentration. Therefore, an optimized combination may lead to better sustaining effect.
Aceves, J.M., Cruz, R., Hernandez, E. (2000). Preparation and characterization of furosemide-Eudragit controlled release systems. Int J Pharm, 195, 45-53. http://dx.doi.org/10.1016/S0378-5173(99)00303-8
Bruce, L.D., Shah, N.H., Malick, A.W., Infeld, M.H., McGinity, J.W.(2000). Properties of hot-melt extruded tablet formulations for the colonic delivery of 5-aminosalicylic acid. Eur J Pharm Biopharm. 59, 85–97. http://dx.doi.org/10.1016/j.ejpb.2004.06.007
Colombo, P., Bettini, R., Santi, P. and Peppas, N.A. (2003). Swellable matrices for controlled drug delivery: gel-layer behavior, mechanisms and optimal performance. Pharm Sci Technol Today, 3,198–204. http://dx.doi.org/10.1016/S1461-5347(00)00269-8
Drooge, D.J., Hinrichs, W.L.J. and Wegman, K.A.M. (2004). Solid dispersions based on inulin for the stabilisation and formulation of Δ9-tetrahydrocannabinol. Eur. J. Pharm. Sci., 21, 511-523. http://dx.doi.org/10.1016/j.ejps.2003.11.014
Goracinova, K., Klisarova, L.J., Simov, A. (1995). Physical characterization and dissolution properties of verapamil HCl coprecipitates. Drug Dev Ind Pharm., 21, 383-391. http://dx.doi.org/10.3109/03639049509048119
Gurnasinghani, M.L., Bhatt, H.R., Lalla, J.K. (1989). Indomethacin delivery from matrix controlled release indomethacin tablets. J Control Rel., 8, 211-222. http://dx.doi.org/10.1016/0168-3659(89)90043-6
Katikaneni, P.R., Upadrashta, S.M., Neau, S.H. and Mitra, A.K. (1995). Ethylcellulose matrix controlled release tablets of a water soluble drug. Int J Pharm.,123, 119–125.
Kidokoro, M., Shah, N.H., Malick, A.W., Infel, M.H., McGinity, J.W. (2001). Properties of tablets containing granulations of ibuprofen and an acrylic copolymer prepared by thermal processes. Pharm Develop Technol., 6, 263–275.
Moffat, A.C., Osselton, M.D., Widdop, B. (2011). Clarke’s analysis of drugs & poisons. 4th ed., UK, Pharmaceutical Press.
Nagarsenker, M.S., Meshram, R.N. and Ramprakash, G. (2000). Solid dispersion of hydroxypropyl b-Cyclodextrin and ketorolac: enhancement of in-vitro dissolution rates, improvement in antiinflammatory activity and reduction in ulcerogenicity in rats. J Pharm Pharmacol, 52, 949- 960. http://dx.doi.org/10.1211/0022357001774831
Palmieri, G.E., Michelini, S., Martino, P.D., Martelli, S. (2000). Polymers with pH-dependent solubility: possibility of use in the formulation of gastroresistant and controlled-release matrix tablet. Drug Dev Ind Pharm., 26, 837–845. http://dx.doi.org/10.1081/DDC-100101307
Pignatello, R., Ferro, M., De Guidi, G., Salemi, G., Vandelli, M.A., Guccione, S., Geppi, M., Forte, C., Puglisi, G. (2001). Preparation, Characterisation and photosensitivity studies of solid dispersions of diflunisal and Eudragit RS100 and RL100. Int J Pharm., 218, 27-42. http://dx.doi.org/10.1016/S0378-5173(01)00597-X
Qui, Y., Zhang, D. (2000). Research and Development Aspects of Oral Controlled Release Systems, In: Wise, D.L.(eds). Handbook of Pharmaceutical Controlled Release Technology, New York, Marcel Dekker Inc., pp 465–503.
Rodriguez, L., Caputo, O., Cini, M., Cavallar, C. and Grecchi, R. (1993). In vitro release of theophylline from directly-compressed matrices containing methacrylic acid copolymers and/or dicalcium phosphate dehydrate. Farmaco, 48, 1597–1604.
Thube, M.W., Shahi, S.R. (2010). Formulation Development and Evaluation of extended release tablets of Pentoxifylline. Int J Pharm Res Dev, 2,1-11.
Tiwari, R., Srivastava, B., Tiwari, G., Rai, A. (2009). Extended release promethazine HCl using acrylic polymers by freeze-drying and spray-drying techniques: formulation considerations. Brazilian J Pharm Sci., 45(4), 829-840. http://dx.doi.org/10.1590/S1984-82502009000400029
Zhu, Y., Shah, N.H., Malick, A.W., Infeld, M.H., McGinity, J.W. (2000). Influence of thermal processing on the properties of chlorpheniramine maleate tablets containing an acrylic polymer. Pharm Dev Technol., 7, 481–489. http://dx.doi.org/10.1208/s12249-010-9378-z
Zijlstra, G.S., Rijkeboer, M. and Drooge, D.J.V. (2007). Characterization of a Cyclosporine solid dispersion for inhalation. AAPS J, 9, E190-E199. http://dx.doi.org/10.1208/aapsj0902021
How to Cite
Articles in Journal of Pharmaceutical Technology, Research And Management (J. Pharm. Technol. Res. Manag.) by Chitkara University Publications are Open Access articles that are published with licensed under a Creative Commons Attribution- CC-BY 4.0 International License. Based on a work at https://jptrm.chitkara.edu.in. This license permits one to use, remix, tweak and reproduction in any medium, even commercially provided one give credit for the original creation.
View Legal Code of the above mentioned license, https://creativecommons.org/licenses/by/4.0/legalcode
View Licence Deed here https://creativecommons.org/licenses/by/4.0/
|Journal of Pharmaceutical Technology, Research And Management by Chitkara University Publications is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work at https://jptrm.chitkara.edu.in