Solubility Enhancement of Simvastatin through Surfactant Addition for Development of Hydrophobic Drug-Loaded Gelatin Hydrogel

https://doi.org/10.22146/ijc.38153

Niswati Fathmah Rosyida(1), Pinandi Sri Pudyani(2), Akhmad Kharis Nugroho(3), Ika Dewi Ana(4), Teguh Ariyanto(5*)

(1) Department of Orthodontics, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
(2) Department of Orthodontics, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
(3) Department of Pharmaceutics, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
(4) Department of Biomedicine, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
(5) Department of Chemical Engineering, Faculty of Engineering, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
(*) Corresponding Author

Abstract


This study aims to synthesize simvastatin hydrogel as drug delivery system with surfactant addition for improving solubility of simvastatin. Surfactants used in the study were the zwitterionic amino acid of arginine and nonionic surface-active agent of polysorbate 80. The solubility study was conducted by pouring of an excess mass of simvastatin into the solution of a surfactant in a conical flask. The sample was shaken up to 72 h in a mechanical water bath shaker at a varied temperature of 25, 40, and 50 °C. The amount of drug dissolved in solution was analyzed by UV/Visible spectrophotometer at 238 nm. The results showed that the simvastatin solubility is profoundly influenced by the surfactant type, surfactant concentration, and temperature. Polysorbate 80 exhibited as a better surfactant than arginine and an enhancement up to 1400 times, in respect of without any addition of a surfactant, was observed. Based on the solubility study, simvastatin-loaded gelatin hydrogel composite was formulated and the characterization (FTIR and SEM) showed the successful impregnation. The hydrogel microparticles of featured swelling indexes in the range of 2–6 for every patch and presented a sustained release profile.


Keywords


hydrogel; simvastatin; solubility; surfactant

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References

[1] Garrett, I.R., and Mundy, G.R., 2002, The role of statins as potential targets for bone formation, Arthritis Res., 4 (4), 237–240.

[2] Ayukawa, Y., Yasukawa, E., Moriyama, Y., Ogino, Y., Wada, H., Atsuta, I., and Koyano, K., 2009, Local application of statin promotes bone repair through the suppression of osteoclasts and the enhancement of osteoblasts at bone-healing sites in rats, Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., 107 (3), 336–342.

[3] Tsubaki, M., Satou, T., Itoh, T., Imano, M., Yanae, M., Kato, C., Takagoshi, R., Komai, M., and Nishida, S., 2012, Bisphosphonate- and statin-induced enhancement of OPG expression and inhibition of CD9, M-CSF, and RANKL expressions via inhibition of the Ras/MEK/ERK pathway and activation of p38MAPK in mouse bone marrow stromal cell line ST2, Mol. Cell. Endocrinol., 361 (1-2), 219–231.

[4] Kaji, H., Naito, J., Inoue, Y., Sowa, H., Sugimoto, T., and Chihara, K., 2008, Statin suppresses apoptosis in osteoblastic cells: Role of transforming growth factor-β-Smad3 pathway, Horm. Metab. Res., 40 (11), 746–751.

[5] Chen, P.Y., Sun, J.S., Tsuang, Y.H., Chen, M.H., Weng, P.W., and Lin, F.H., 2010, Simvastatin promotes osteoblast viability and differentiation via Ras/Smad/Erk/BMP-2 signaling pathway, Nutr. Res., 30 (3), 191–199.

[6] Schachter, M., 2005, Chemical, pharmacokinetic and pharmacodynamic properties of statins: An update, Fundam. Clin. Pharmacol., 19 (1), 117–125.

[7] Kheirallah, M., and Almeshaly, H., 2016, Simvastatin, dosage and delivery system for supporting bone regeneration, an update review, J. Oral Maxillofac. Surg. Med. Pathol., 28 (3), 205–209.

[8] Matsuyama, K., Nakagawa, K., Nakai, N., Konishi, Y., Nishikita, M., Tanaka, H., and Uchida, T., 2002, Evaluation of myopathy risk for HMG-CoA reductase inhibitors by urethane infusion method, Biol. Pharm. Bull., 25 (3), 346–350.

[9] Oryan, A., Kamali, A., and Moshiri, A., 2015, Potential mechanisms and applications of statins on osteogenesis: Current modalities, conflicts and future directions, J. Controlled Release, 215, 12–24.

[10] Kaur, G., and Mehta, S.K., 2017, Developments of Polysorbate (Tween) based microemulsions: Preclinical drug delivery, toxicity and antimicrobial applications, Int. J. Pharm., 529 (1-2), 134–160.

[11] Kim, Y.H., and Tabata, Y., 2015, Dual-controlled release system of drugs for bone regeneration, Adv. Drug Deliv. Rev., 94, 28–40.

[12] Hoare, T.R., and Kohane, D.S., 2008, Hydrogels in drug delivery: Progress and challenges, Polymer, 49 (8), 1993–2007.

[13] Savjani, K.T., Gajjar, A.K., and Savjani, J.K., 2012, Drug solubility: Importance and enhancement techniques, ISRN Pharm., 2012, 195727.

[14] Yan, J., Yin, Q., Jiang, C., Gong, J., Zhang, M., Wang, Y., Hou, B., and Hao, H., 2015, Solution thermodynamics of simvastatin in pure solvents and binary solvent mixtures, Fluid Phase Equilib., 406, 77–90.

[15] Sirtori, C.R., 2014, The Pharmacology of statins, Pharmacol. Res., 88, 3–11.

[16] Troy, D.B., and Beringer, P., 2006, Remington: The Science and Practice of Pharmacy, Lippincott Williams & Wilkins, Philadelphia, US.

[17] Jia, Z., Zhang, Y., Chen, Y.H., Dusad, A., Yuan, H., Ren, K., Li, F., Fehringer, E.V., Purdue, P.E., Goldring, S.R., Daluiski, A., and Wang, D., 2015, Simvastatin prodrug micelles target fracture and improve healing, J. Controlled Release, 200, 23–34.

[18] Rosyida, N.F., Ariyanto, T., Pudyani, P. S., and Ana, I.D., 2018, Preparation of simvastatin hydrogel through arginine addition for drug delivery system, MATEC Web. Conf., 156, 01002.

[19] Hirano, A., Kameda, T., Arakawa, T., and Shiraki, K., 2010, Arginine-assisted solubilization system for drug substances: Solubility experiment and simulation, J. Phys. Chem. B, 114 (42), 13455–13462.

[20] Wolf, R.B., Cavins, J.F., Kleiman, R., and Black, L.T., 1982, Effect of temperature on Soybean Seed constituents: Oil, protein, moisture, fatty acids, amino acids and sugars, J. Am. Oil Chem. Soc., 59 (5), 230–232.

[21] Tanigo, T., Takaoka, R., and Tabata, Y., 2010, Sustained release of water-insoluble simvastatin from biodegradable hydrogel augments bone regeneration, J. Controlled Release, 143 (2), 201–206.

[22] Yasasvini, S., Anusa, R., Vedhahari, B., Prabhu, P., and Ramyadevi, D., 2016, Topical hydrogel matrix loaded with simvastatin microparticles for enhanced wound healing activity, Mater. Sci. Eng., C, 72, 160–167.

[23] Thambi, T., Li, Y., and Lee, D.S., 2017, Injectable hydrogels for sustained release of therapeutic agents, J. Controlled Release, 267, 57–66.



DOI: https://doi.org/10.22146/ijc.38153

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