In-situ crystallization of sildenafil during ionic crosslinking of alginate granules

Seungvin Cho; Jeong Won Kang; Jonghwi Lee

Korean Journal of Chemical Engineering, Vol.37, No.10, 1726-1731, October, 2020

DOI10.1007/s11814-020-0580-8 Export Citation

In-situ crystallization of sildenafil during ionic crosslinking of alginate granules

Seungvin Cho, Jeong Won Kang¹, and Jonghwi Lee^†

Department of Chemical Engineering and Materials Science, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 06974, Korea
¹Department of Chemical and Biological Engineering, Korea University, 145 Anam-ro, Sungbuk-gu, Seoul 02841, Korea

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Hydrogel particles containing drug crystals were investigated for the development of drug formulations with improved processability, bioavailability, and physical stability. However, crystal engineering inside hydrogel particles has been limited due to various difficulties involved in the preparation processes and their control. This study demonstrates the crosslinking of alginate granules and the simultaneous crystallization of a drug, sildenafil, inside the granules by using a simple and scalable preparation technique. The particle size of the drug crystals was successfully decreased to the submicron range while their crystallinity could be controlled by the processing parameters. Moreover, these results are shown to be due to the strong interactions between the polymer chains and the drug as well as the diffusion-limited processes of solvent, antisolvent, sildenafil, alginate, and crosslinking ions (Ca2+). This simple crystallization technique will be useful for the development of novel drug delivery systems based on hydrogels and drug crystallites.

Keywords:Drug Delivery;Hydrogel;Alginate;Sildenafil;Polymer-directed Crystallization;Granule

[References]

Ma C, Shi Y, Pena DA, Peng L, Yu G, Angew. Chem.-Int. Edit., 54, 7376 (2015)
Lee PI, J. Control. Release, 2, 277 (1985)
Kim BS, Leong J, Yu SJ, Cho Y, Park CG, Kim DH, Ko E, Im SG, Lee J, Kim YJ, Small, 15(21), 190076 (2019)
Zhou J, Wang G, Zou L, Tang L, Marquez M, Hu Z, Biomacromolecules, 9, 142 (2007)
Serpe MJ, Yarmey KA, Nolan CM, Lyon LA, Biomacromolecules, 6(1), 408 (2005)
Juric D, Rohner NA, von Recum HA, Macromol. Biosci., 19, 180024 (2019)
Lee H, Jeong Y, Park TG, Biomacromolecules, 8(12), 3705 (2007)
Wu L, Zhang J, Watanabe W, Adv. Drug Deliv. Rev., 63, 456 (2011)
Badruddoza AZM, Godfrin PD, Myerson AS, Trout BL, Doyle PS, Adv. Healthc. Mater., 5, 1960 (2016)
Gu T, Yeap EW, Cao Z, Ng DZ, Ren Y, Chen R, Khan SA, Hatton TA, Adv. Healthc. Mater., 7, 170079 (2018)
Acevedo DA, Ling J, Chadwick K, Nagy ZK, Cryst. Growth Des., 16, 4263 (2016)
Eral HB, Lopez-Mejias V, O’Mahony M, Trout BL, Myerson AS, Doyle PS, Cryst. Growth Des., 14, 2073 (2014)
Mealy JE, Chung JJ, Jeong HH, Issadore D, Lee D, Atluri P, Burdick JA, Adv. Mater., 30, 170591 (2018)
Choi JY, Yoo JY, Kwak HS, Nam BU, Lee J, Curr. Appl. Phys., 5(5), 472 (2005)
Gao L, Liu G, Ma J, Wang X, Zhou L, Li X, Wang F, Pharm. Res., 30, 307 (2013)
Keck CM, Muller RH, Eur. J. Pharm. Biopharm., 62, 3 (2006)
Shia LL, Xua WJ, Caoa QR, Yanga M, Cui JH, J. Pharm. Sci., 69, 327 (2014)
Van Eerdenbrugh B, Van den Mooter G, Augustijns P, Int. J. Pharm., 364, 64 (2008)
Lu Y, Lv Y, Li T, Adv. Drug Deliv. Rev., 143, 1 (2019)
Chai Z, Ran D, Lu L, Zhan C, Ruan H, Hu X, Xie C, Jiang K, Li J, Zhou J, ACS Nano, 13, 5591 (2019)
Pawar VK, Singh Y, Meher JG, Gupta S, Chourasia MK, J. Control. Release, 183, 51 (2014)
Lee J, Cheng Y, J. Control. Release, 111, 185 (2006)
Braig V, Konnerth C, Peukert W, Lee G, Int. J. Pharm., 554, 54 (2019)
Chung NO, Lee MK, Lee J, Int. J. Pharm., 437, 42 (2012)
Lim DG, Jung JH, Ko HW, Kang E, Jeong SH, ACS Appl. Mater. Interfaces, 8, 23558 (2016)
Lee MK, Kim MY, KimS, Lee J, J. Pharm. Sci., 98, 4808 (2009)
Kim S, Lee J, Int. J. Pharm., 397, 218 (2010)
Chin WWL, Parmentier J, Widzinski M, Tan EH, Gokhale R, J. Pharm. Sci., 103, 2980 (2014)
Poornachary SK, Han G, Kwek JW, Chow PS, Tan RB, Cryst. Growth Des., 16, 749 (2016)
Lopez-Mejias V, Knight JL, Brooks CL, Matzger AJ, Langmuir, 27(12), 7575 (2011)
Frank DS, Matzger AJ, Cryst. Growth Des., 17, 4056 (2017)
Lee MK, Lee H, Kim IW, Lee J, Die Pharmazie, 66, 766 (2011)
Choi H, Lee H, Lee MK, Lee J, J. Pharm. Sci., 101, 2941 (2012)
Li RH, Altreuter DH, Gentile FT, Biotechnol. Bioeng., 50(4), 365 (1996)
Favre E, Leonard M, Laurent A, Dellacherie E, Colloids Surf. A: Physicochem. Eng. Asp., 194, 197 (2001)
Song RQ, Colfen H, Adv. Mater., 22(12), 1301 (2010)
Lee H, Lee J, J. Ind. Eng. Chem., 21, 1183 (2015)
Takeuchi H, Yasuji T, Yamamoto H, Kawashima Y, Pharm. Dev. Technol., 5, 355 (2000)
Melnikov P, Corbi PP, Cuin A, Cavicchioli M, Guimaraes WR, J. Pharm. Sci., 92, 2140 (2003)
Xia M, Kang SM, Lee GW, Huh YS, Park BJ, J. Ind. Eng. Chem., 73, 306 (2019)

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