Mesoporous tablet-shaped potato starch aerogels for loading and release of the poorly water-soluble drug celecoxib

doi:10.1016/j.cjche.2020.03.040

摘要/Abstract

摘要： In this study, after determination of the optimal values of the effective parameters in the synthesis using experimental design software, tablet-shaped potato starch aerogels were synthesized at the optimal condition in order to be used as a drug carrier. The celecoxib, as the model drug, was loaded into the aerogel matrix during the solvent exchange step. FTIR (Fourier Transform Infrared Spectroscopy), FESEM and HRTEM (Transmission Electron Microscopy) analyses showed that celecoxib has been successfully loaded into aerogel matrix. Also, XRD analysis showed that most of the celecoxib has been loaded in amorphous form. In vitro studies were performed in both simulated gastric and intestinal fluids. The release kinetics showed that the loaded celecoxib dissolved faster than crystalline celecoxib. At rotational speed of 100 r·min^-1, about 26% and 50% and at rotational speed of 50 r·min^-1, about 20% and 42% drug was released during the first 30 min of soaking in the simulated gastric fluid and simulated intestinal fluid, respectively. The release of the mentioned drug was increased up to 60% and 98% at a rotational speed of 100 r·min^-1 and up to 46% and 93% at a rotational speed of 50 r·min^-1 at the end of 5 h in the simulated gastric fluid and simulated intestinal fluid, respectively. It could be concluded that potato starch aerogels can be very useful in many drug delivery applications along with conventional micronization techniques. Modeling of release data showed that the release kinetics follows the Korsmeyer Peppas model, which considers phenomena of matrix erosion and drug diffusion.

关键词: Adsorption isotherm, Celecoxib, Drug delivery, Optimization, Starch aerogel

Abstract: In this study, after determination of the optimal values of the effective parameters in the synthesis using experimental design software, tablet-shaped potato starch aerogels were synthesized at the optimal condition in order to be used as a drug carrier. The celecoxib, as the model drug, was loaded into the aerogel matrix during the solvent exchange step. FTIR (Fourier Transform Infrared Spectroscopy), FESEM and HRTEM (Transmission Electron Microscopy) analyses showed that celecoxib has been successfully loaded into aerogel matrix. Also, XRD analysis showed that most of the celecoxib has been loaded in amorphous form. In vitro studies were performed in both simulated gastric and intestinal fluids. The release kinetics showed that the loaded celecoxib dissolved faster than crystalline celecoxib. At rotational speed of 100 r·min^-1, about 26% and 50% and at rotational speed of 50 r·min^-1, about 20% and 42% drug was released during the first 30 min of soaking in the simulated gastric fluid and simulated intestinal fluid, respectively. The release of the mentioned drug was increased up to 60% and 98% at a rotational speed of 100 r·min^-1 and up to 46% and 93% at a rotational speed of 50 r·min^-1 at the end of 5 h in the simulated gastric fluid and simulated intestinal fluid, respectively. It could be concluded that potato starch aerogels can be very useful in many drug delivery applications along with conventional micronization techniques. Modeling of release data showed that the release kinetics follows the Korsmeyer Peppas model, which considers phenomena of matrix erosion and drug diffusion.

Key words: Adsorption isotherm, Celecoxib, Drug delivery, Optimization, Starch aerogel

Akbar Mohammadi, Jafarsadegh Moghaddas. Mesoporous tablet-shaped potato starch aerogels for loading and release of the poorly water-soluble drug celecoxib[J]. 中国化学工程学报, 2020, 28(7): 1778-1787.

Akbar Mohammadi, Jafarsadegh Moghaddas. Mesoporous tablet-shaped potato starch aerogels for loading and release of the poorly water-soluble drug celecoxib[J]. Chinese Journal of Chemical Engineering, 2020, 28(7): 1778-1787.

参考文献

[1] K. Stamatopoulos, H.K. Batchelor, F. Alberini, J. Ramsay, M.J.H. Simmonset, Understanding the impact of media viscosity on dissolution of a highly water soluble drug within a USP 2 mini vessel dissolution apparatus using an optical planar induced fluorescence (PLIF) method, Int. J. Pharm. 495(1) (2015) 362-373.
[2] Z. Ulker, C. Erkey, An emerging platform for drug delivery:Aerogel based systems, J. Control. Release 177(2014) 51-63.
[3] C. Barbé, J. Bartlett, L. Kong, K. Finnie, H. Qiang, M. Larkin, S. Calleja, A. Bush, G. Calleja, Silica particles:A novel drug-delivery system, Adv. Mater. 16(21) (2004) 1959-1966.
[4] H. Jonassen, Polysaccharide based nanoparticles for drug delivery applications, phD Thesi, University of Oslo, Norway, 2014.
[5] Z. Liu, Y. Jiao, Y. Wang, C. Zhou, Z. Zhang, Polysaccharides-based nanoparticles as drug delivery systems, Adv. Drug Deliv. Rev. 60(15) (2008) 1650-1662.
[6] Z. Ulker, C. Erkey, An advantageous technique to load drugs into aerogels:Gas antisolvent crystallization inside the pores, J. Supercrit. Fluids 120(2) (2017) 310-319.
[7] M. Alnaief, I. Smirnova, Effect of surface functionalization of silica aerogel on their adsorptive and release properties, J. Non-Cryst. Solids 356(33-34) (2010) 1644-1649.
[8] L. Amirkani, J. Moghaddas, H. Jafarizadeh-Malmiri, Candida rugosa lipase immobilization on magnetic silica aerogel nanodispersion, RSC Adv. 6(15) (2016) 12676-12687.
[9] I. De Marco, E. Reverchon, Starch aerogel loaded with poorly water-soluble vitamins through supercritical CO₂ adsorption, Chem. Eng. Res. Des. 119(2017) 221-230.
[10] C.A. García-González, M. Alnaief, I. Smirnova, Polysaccharide-based aerogels-Promising biodegradable carriers for drug delivery systems, Carbohydr. Polym. 86(4) (2011) 1425-1438.
[11] U. Guenther, I. Smirnova, R.H.H. Neubert, Hydrophilic silica aerogels as dermal drug delivery systems-Dithranol as a model drug, Eur. J. Pharm. Biopharm. 69(3) (2008) 935-942.
[12] Z. Novak, M. Habulin, V. Krmelj, Z. Knez, Silica aerogels as supports for lipase catalyzed esterifications at sub-and supercritical conditions, J. Supercrit. Fluids 27(2) (2003) 169-178.
[13] P. Veres, M. Keri, I. Bányai, I. Lázár, I. Fábián, C. Domingo, J. Kalmár, Mechanism of drug release from silica-gelatin aerogel-Relationship between matrix structure and release kinetics, Colloids Surf. B:Biointerfaces 152(2017) 229-237.
[14] T. Mehling, I. Smirnova, U. Guenther, R.H.H. Neubert, Polysaccharide-based aerogels as drug carriers, J. Non-Cryst. Solids 355(2009) 2472-2479.
[15] C.A. García-González, I. Smirnova, Use of supercritical fluid technology for the production of tailor-made aerogel particles for delivery systems, J. Supercrit. Fluids 79(2013) 152-158.
[16] C.A. García-González, M. Jin, J. Gerth, C. Alvarez-Lorenzo, I. Smirnova, Polysaccharide-based aerogel microspheres for oral drug delivery, Carbohydr. Polym. 117(2015) 797-806.
[17] M. Alnaief, I. Smirnova, In situ production of spherical aerogel microparticles, J. Supercrit. Fluids 55(3) (2011) 1118-1123.
[18] S.S. Kistler, Coherent expanded aerogels and jellies, Nature (1931) 127-741.
[19] A. Ubeyitogullari, O.N. Ciftci, Formation of nanoporous aerogels from wheat starch, Carbohydr. Polym. 147(2016) 125-132.
[20] X. Chang, D. Chen, X. Jiao, Starch-derived carbon aerogels with high-performance for sorption of cationic dyes, Polym. 51(2010) 3801-3807.
[21] I.D. Marco, L. Baldino, S. Cardea, E. Reverchon, Supercritical gel drying for the production of starch aerogels for delivery systems, Chemical Engineering Transactions 43(2015) 307-312.
[22] A. Demilecamps, Synthesis and characterization of polysaccharide-silica composite aerogels for thermal superinsulation, Ph. D. Thesis, Mines Paris Tech., France, 2016.
[23] A. Veronovski, G. Tkalec, Z. Knez, Z. Novak, Characterisation of biodegradable pectin aerogels and their potential use as drug carriers, Carbohydr. Polym. 113(2014) 272-278.
[24] L. Wang, M. Sánchez-Soto, T. Abt, Properties of bio-based gum Arabic/clay aerogels, Industrial Crops and Products 91(2016) 15-21.
[25] G.M. Glenn, D.J. Stern, Starch-based microcellular foam, U.S. Pat, 5958889A, 1999.
[26] N.L. Vanier, S.L.M. Halal, A.R.G. Dias, E.R. Zavareze, Molecular structure, functionality and applications of oxidized starches:A review, Food Chem. 221(2017) 1546-1559.
[27] D. Vashisht, A. Pandey, A. Hermenean, M.J. Yánez-Gascón, H. Pérez-Sánchez, K.J. Kumar, Effect of dry heating and ionic gum on the physicochemical and release properties of starch from Dioscorea, Int. J. Biol. Macromol. 95(2017) 557-563.
[28] G. Chawla, P. Gupta, R. Thilagavathi, A.K. Chakraborti, A.K. Bansal, Characterization of solid-state forms of celecoxib, Eur. J. Pharm. Sci. 20(3) (2003) 305-317.
[29] G.V.M.M. Babu, V.G. Shankar, K.H. Sankar, A. Seshasayana, N.K. Kumar, K.V.R. Murthy, Development of dissolution medium for a poorly water soluble drug, celecoxib, Indian J. Pharm. Sci. 64(2002) 588-591.
[30] B. Vijayakumar, V. Kannappan, V. Sathyanarayanamoorthi, DFT analysis and spectral characteristics of celecoxib a potent COX-2 inhibitor, J. Mol. Struct. 1121(2016) 16-25.
[31] J.M. Bock, S.G. Menon, L.L. Sinclair, N.S. Bedford, P.C. Goswami, F.E. Domann, D.K. Trask, Celecoxib toxicity is cell cycle phase specific, Cancer Res. 67(8) (2007) 3801-3808.
[32] M. Kern, D. Schubert, D. Sahi, M.M. Schoneweiß, I. Moll, A.M. Haugg, H.P. Dienes, K. Breuhahn, P. Schirmacher, Proapoptotic and antiproliferative potential of selective cyclooxygenase-2 inhibitors in human liver tumor cells, Hepatology 36(4) (2002) 885-894.
[33] G. Tkalec, Ž. Knez, Z. Novak, Fast production of high-methoxyl pectin aerogels for enhancing the bioavailability of low-soluble drugs, J. Supercrit. Fluids 106(2015) 16-22.
[34] D.D. Lovskaya, A.E. Lebedev, N.V. Menshutina, Aerogels as drug delivery systems:In vitro and in vivo evaluations, J. Supercrit. Fluids 106(2015) 115-121.
[35] A. Khazraei, A. Tarlani, N. Naderi, J. Muzart, Z. Abdulhameed, M. Slami-Moghadam, Enhanced release and drug delivery of celecoxib into physiological environment by the different types of nanoscale vehicles, Applied Surface Science 422(2017) 873-882.
[36] P. Veres, A.M. López-Periago, I. Lázár, J. Saurina, C. Domingo, Hybrid aerogel preparations as drug delivery matrices for low water-solubility drugs, Int. J. Pharm. 496(2015) 360-370.
[37] V.S.S. Gonçalves, P. Gurikov, J. Poejo, A.A. Matias, S. Heinrich, C.M.M. Duarte, I. Smirnova, Alginate-based hybrid aerogel microparticles for mucosal drug delivery, Eur. J. Pharm. Biopharm. 107(2016) 160-170.
[38] C. Maderuelo, A. Zarzuelo, J.M. Lanao, Critical factors in the release of drugs from sustained release hydrophilic matrices, J. Control. Release 154(2011) 2-19.